Continuity of care: Perspectives of participants, investigators, and healthcare providers after trial completion in South Africa

Continuity of care: Perspectives of participants, investigators, and healthcare providers after trial completion in South Africa | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Continuity of care: Perspectives of participants, investigators, and healthcare providers after trial completion in South Africa Nyeleti Babitjie Mthombeni, Eric Decloedt, Elizabeth Allen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9005712/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Despite decades of updates to frameworks and guidelines for the conduct of clinical trials, what happens to participants when a trial ends remains a persistent ethical dilemma. This study evaluated the views of investigators, healthcare providers (HCPs), and participants regarding post-trial care (PTC) for participants on chronic treatment after trial completion. Method This study involved 38 interviews with 17 investigators, 15 trial participants and six HCPs from 15 trial sites in South Africa. Six of the investigators were also HCPs to the participants, and seven sites were in state or public facilities. Results Post-trial care was unstructured, informal, and not included in trial protocols or budgets. The roles of investigators and HCPs were unclear. Study completion letters intended for HCPs were not received, and investigators arranged follow-up appointments at facilities where they had no ongoing responsibility. Participants continued with their pretrial standard of care (SoC) without the beneficial trial interventions. Discontinuing the intervention mainly affected those with Rheumatoid Arthritis (RA). Without post-trial follow-up (PTFU), the effective implementation of post-trial care for participants is unknown, and no quality of care or stability of treatment could be confirmed after switching treatment and returning to the pre-trial SoC. Investigators and HCPs disputed the concept of post-trial care and supported continuity of care (CoC). CoC was seen as a shared responsibility between investigators and HCPs and dependent on five interrelated processes: first, continued satisfactory quality of care comparable to trial standards at trial exit; second, access to optimal treatment options; third, ensuring effective handover to routine HCPs with adequate information, forth, conducting PTFU ensure stability once participants initiate post-trial care and last, involvement of HCP. Conclusion Our findings propose reframing post-trial care as CoC by expanding the focus beyond the post-trial phase to the entire lifecycle of a trial. By having the trial end in mind, CoC should already be implemented at enrolment and continued until trial conclusion. Recommendations: This study calls on policymakers, sponsors, investigators, and regulators to move beyond a narrow focus on the post-trial phase, primarily aimed at providing access to trial interventions, and adopt a practical, implementable, fundable, and auditable CoC process. Continuity of care ongoing care post-trial obligations after care linkage to care post-trial access investigator-healthcare provider post-trial follow-up post-trial healthcare Figures Figure 1 Background The enduring dilemma of managing trial participants after they complete a trial is one that researchers, trial sponsors, policymakers, regulators, and ethics committees have struggled with for decades. Various terms describe what happens after the trial, such as post-trial responsibilities, post-trial obligations, post-trial care (PTC), transition care, care after research, responsible transitioning post-trial provisions, and linkage to care ( 1 – 9 ). All these terms aim to encapsulate what should happen to trial participants after the trial, especially those who need care to safeguard their health and well-being ( 3 ). In general, the trial duration is short, often enrolling participants who are reliant on chronic treatment managed by their routine health care providers (HCPs). Once in the trial, investigators are responsible for management, often at facilities outside the routine health care structures of the participants ( 10 ). During the trial, routine standard of care (SoC) treatments may be replaced, switched, paused, or continued as per the trial design ( 11 – 13 ). Participants are therefore exposed to the intervention, which may include the experimental medicine or device, or a placebo ( 3 , 14 ). At the end of the trial, care may continue with the trial intervention or replaced by SoC provided by routine health care facilities ( 4 ). When post-trial provisions were not adequately planned, participants express emotional distress, such as sadness, anger, disappointment, anxiety, hopelessness, despair and abandonment ( 13 , 15 – 17 ). Participants fear losing the quality of care gained during the trial and the possibility of receiving inferior SoC in non-research facilities ( 1 , 15 ). Furthermore, the lack of planned post-trial provisions affects the trial team when they witness their participants' distress ( 16 , 17 ). Post-trial provision processes encompass multiple activities, including planning for access to an effective and safe SoC intervention ( 2 , 9 ), facilitating participants' reintegration into care following the trial ( 2 , 14 ), Furthermore, it includes arranging alternative SoC interventions ( 8 , 14 ), providing adequate medical care for trial-related adverse events ( 18 ), and implementing post-trial follow-up (PTFU) to detect the long-term impact or hazards of the trial intervention ( 19 ). In addition, if the intervention is proven to be beneficial, continuation of the investigational medication may be provided through post-trial access (PTA) ( 9 , 20 ). Researchers and pharmaceutical sponsors rely on international ethical guidelines, such as the World Medical Association (WMA) Declaration of Helsinki, to prepare for trial closure ( 16 , 21 ). However, these guidelines have been criticised for neglecting overall post-trial care ( 7 , 22 – 25 ). This is because they focus primarily on other aspects of trial conduct, such as recruitment, informed consent and ( 16 ) on PTA ( 5 , 16 , 20 , 21 , 26 ). It is therefore not surprising that this is echoed in national guidelines, such as the South African Health Products Regulatory Authority (SAHPRA) Continued Access guidelines, which also focus on PTA, with no consideration of the overall post-trial care ( 27 ). Delivering post-trial care involves multiple stakeholders. The WMA Declaration of Helsinki (2013) names sponsors, researchers, and host-country governments as responsible parties ( 28 , 29 ). These guidelines exclude routine HCPs, although they are responsible for routine care. The Council for International Organisations of Medical Sciences (CIOMS) outlines ethical guidelines for health-related research involving humans, requiring researchers and sponsors to explain how care will be provided for other conditions but not defining how HCPs should be engaged ( 3 ). Literature also focuses mainly on the role of HCPs as recruiters or potential investigators, not as role players in ongoing or post-trial care ( 13 , 30 , 31 ). Yet the documented experiences of the trial participants highlights practical challenges faced when HCPs were not part of the research process. Some reported being mistreated or judged for participating in a clinical trial, leading them to discontinue treatment ( 13 ). The latest International Council for Harmonisation (ICH) GCP E6 (R3) acknowledges that appropriately qualified HCPs may provide medical care during the trial period in line with local regulations ( 18 ). Although the effects of post-trial care are acknowledged, limited research addresses its impact on patients at the conclusion of clinical trials. There is sparse data on how these processes affect African participants with chronic conditions. As part of a larger study involving trial participants, we explored the experiences of investigators and HCPs in providing post-trial care and its impact on clinical trial participants receiving chronic treatment for diabetes mellitus (DM), rheumatoid arthritis (RA), and cardiovascular disease (CVD). Methods The aim, design and setting of the study The study examined how investigators and HCPs manage participants' care after the trial and how the processes impacted the participants. We employed a qualitative method to explore the perspectives of investigators, routine HCPs, and participants with chronic conditions (DM, RA, and CVD). Data collection We conducted semi-structured interviews with 38 respondents: 36 virtually and 2 face-to-face, lasting 30–60 minutes, between 2021 and 2023. All interviews were audio-recorded via Microsoft Teams® and transcribed verbatim using NVivo®; the transcripts were checked against the recordings for accuracy ( 41 ). The interview guides (available on request) were based on the research aims and relevant literature ( 1 , 13 , 15 – 17 , 32 – 38 ) and included open-ended questions with prompts. As new insights were identified, the guides were updated. The participants were reimbursed for their time. Study population and sampling The sample comprised of phase III adult clinical trials in RA, DM, and CDV conducted in South Africa between 1 January 2018 and 31 December 2020. Seventy-five such trials were identified on ClinicalTrials.gov ( 39 ). From these 75, we identified the trial sites and investigators involved using TrialTrove® ( 40 ). A total of 20 trials and 142 investigators were identified. The trial staff assisted with recruiting 15 participants for the identified trials. The participants, in turn, identified their HCPs or health care facilities that provided treatment post-trial. Sampling The study used convenience sampling, and investigators who responded to the invitation were included. The researcher maintained a reflexive journal during the interviews, recording key insights and reflections that guided the evaluation of information power and saturation. Data analysis Thematic analysis followed Braun and Clarke’s framework ( 41 , 42 ). An inductive coding approach was used to identify and organise recurring patterns within the data. These patterns were grouped into overarching themes that reflected the meanings conveyed in participants’ narratives. Verbatim quotations were used to illustrate and support each theme. Reflexive practices were applied through iterative debriefing sessions with coauthors, enhancing the credibility of the findings. The investigators are identified in this document by a five-digit code (e.g., PB005 or PR005). The PBs denote sites in public facilities, while the PRs denote sites in private facilities. Participants are identified by an 11-digit code (e.g., PB005–PRT005) that links them to their investigator. The HCPs are identified by an 11-digit code (e.g., HCP004_PB006) that associates them with investigators. Results Fifteen research sites across five South African provinces participated: the Western Cape [Cape Town ( 6 ), George ( 1 )], Free State [Bloemfontein ( 1 )], Gauteng [cities: Johannesburg ( 4 ) and Pretoria ( 2 )], and Mpumalanga [Nelspruit ( 1 )]. There were 38 respondents, including 17 research staff, 15 clinical trial participants, and 6 HCPs. The 17-site staff consisted of 11 medical doctors and 6 research nurses across the sites, referred to here as investigators. Eight sites were in private facilities, whilst 7 were in public facilities or recruited participants from public facilities. All investigators had more than 10 years of trial experience. The participant group consisted of 15 individuals, 12 females and 3 males, with a mean age of 60 years. Six reported that the investigator was their HCP, and 9 indicated consulting HCPs from different facilities. The HCP group consisted of 6 medical doctors, 2 of whom worked in private facilities providing routine healthcare and four from public or state-run facilities. The HCP and investigator narratives of post-trial care, which were equated with a process of continuity of care (CoC), with 5 sub-themes (Fig. 1 ). First, after the trial, care should be equivalent to that during the trial. This sub-theme is described as continued satisfactory quality of care. Second, CoC depends on accessible treatment options. Third, a referral and information transfer process (a handover subtheme), and fourth, post-trial follow-up to ensure stability. The fifth subtheme is involvement of HCPs as outlined in the figure below. Defining Post-trial Care Investigators and HCPs emphasised the complexity and the persistent neglect of end-of-trial processes. As PB002 stated, “ I think you are going into difficult territory, …it [has] always been the area of trials which is not as well managed ”. HCPs questioned the very label “post-trial care”, arguing that it cements a false boundary and fails to solve the real problem. Instead, they called for a model of CoC that follows the participant beyond trial exit: “ I think to label anything as post-trial care would result in the current situation continuing to happen… [There] should be a continuation …” (HCP004_PB006). Investigators echoed concerns about a lack of continuity, expressing, for example, “ falling in between the cracks ” and “ just left to their own devices ” by (PR006) or “dropping back like a hot potato ” by (PB003), articulating their discontent. PB003 stressed the need for a defined mechanism to ensure continuity, whereas PR004 judged the absence of such a mechanism as “ not ethical and not responsible ”. Continued satisfactory quality of care When the trial ended, the participants returned to routine SoC. As one participant noted, “ … the trial ended… I was referred to the clinic ” (PB005-PRT004). HCPs echoed this: “ We go back to what would have happened even before “(HCP005_PR001). An investigator also attested, “ Prof returned them … ” (PB005). The participants described a stark contrast between quality of life during the trial and after the trial: “ I didn’t get flare-ups…I had eight years of absolute pleasure and joy ” (PR006–PRT013). As such, after trial discontinuation, some experienced a decrease in quality of life: “ I took the same treatment as before ; it took me a while for me to feel the pains again ” (PB006-PRT016). HCPs described witnessing this return to pretrial conditions. “ Terrible, devastating, and not just with terrible pain and disability but with also just a hopelessness. … it's such an emotional rollercoaster … there's a drug that works and then suddenly It's been taken out from underneath you. It's terrible ” (HCP003_PB006). Investigators and HCPs described that satisfactory care requires transitioning to options suitable for the condition but could not confirm whether satisfactory care was achieved because there was no structured follow-up process. However, the HCPs also indicated that some participants deteriorated after switching to SoC: “ Very often when they come off the trials, they flare ” (HCP003_ PB006), and there were consequences for patients who continued with suboptimal SoC: “Generally, patients just live their lives with terrible, uncontrolled disease ” (HCP003_ PB006). Investigators and HCPs suggested establishing a follow-up process to monitor participants after the trial, which is described in detail in subtheme four, PTFU. Access to optimal treatment options All participants were on SoC treatment before the trial, and the SoC was provided either by the state or medical aid. The SoC was often described as suboptimal, encouraging patients to enrol for trial participation: “ I was bedridden, …. nothing seemed to help me, and somebody told me that I must try the trial centre ”. (PR006-PRT011) After the trial, some participants received limited-duration post-trial access (PTA). PTA was more readily available for RA patients, limited for DM patients, and uncommon for CVD participants. Eventually, all participants returned to the SoC, which depended on the treatment option available and accessible. Returning to SoC occurred to both private and state participants. Some participants were able to access other alternative treatments after upgrading their medical insurance coverage or motivation at state clinics. “It might not be the exact same…there are alternatives, they lead to the level of care that the patients have at the moment” (PR005). At the end of the trial, some treatments were available in South Africa; however, they were not accessible to participants. Barriers to access also depended on whether the participant received care from the state or had medical insurance. Barriers to access in state facilities were specific treatment protocols predominantly informed by affordability. HCPs managing state patients reported following national-level standard treatment protocols. This treatment protocol did not regard trial participation as a priority for access: “ Not guaranteed… we have to put them through the same process… some might not fulfil the criteria ” (HCP006_BP002). An additional barrier was the cost of medicines once marketed. As one investigator noted, “ It became available a couple of months after the trial… it was R10 000 (579.61 USD) a month, and the medical aids do not pay for that; there is just no way of the patients having access to the medication post-trial ” (PR008). The participants expressed dismay at the pricing of some of the medicines for which they contributed trial data, stating that only worthy people could afford the exorbitantly priced medicines: “W ho can pay R10,000 (579.61 USD) … you must be ‘Harry Oppenheimer’ , [South African billionaire] ” (PR006-PRT014). The participants recommended making medicines affordable, calling out the manufacturers to take initiative if they indeed cared, “Nothing’s too expensive if you want to help right, you try by all means to give out the help” (PB006–PRT016). Another barrier cited by investigators was state facilities not being able to provide SoC as per international treatment guidelines, as some medicines were not listed in South Africa's national essential medicines list and standard treatment guidelines, as expressed: “ Dipeptidyl peptidase 4 (DPP-4) inhibitors have been available for 10 years … yet these drugs aren’t available ” (PR004). HCPs and investigators implemented solutions to ensure access to treatment, such as motivating for alternatives at local Hospital Pharmacy and Therapeutics Committees or, in the private sector, participants upgraded their medical insurance: “ She knew that she would be able to upgrade and then get a different biologic on her medical aid ” (PR006). HCPs reported that persuasion and motivation could sometimes secure access to treatment: “ Sometimes I have managed to persuade the state's pharmacy and therapeutics committee to give them another biologic and that I have been successful in a few cases ” (HCP003_PB006). In the state sector, HCPs also noted that it was possible to adjust doses within the SoC to improve outcomes. Despite the barriers indicated, both HCPs and investigators emphasised their obligation to act in the best interest of patients: “We just must do our best with the drugs we have ” (HCP003_ PB006). Nonetheless, investigators and HCPs stressed that, before enrolment, participants were clearly informed that they might return to their previous SoC without continued access to trial treatments. “ They also understood from the beginning, … for three years, we explained … there was no planning for more long-term access; they were all fine with it ”. (PB005). HCPs corroborated this narrative, highlighting that careful counselling on risks, uncertainty, and the experimental nature of trials was provided to participants at referrals: “ It is important for us to explain that it’s sort of experimenting. I talk to them carefully in advance ” (HCP006_BP002). The participants also alluded to their knowledge that the trial was only short-term: “ Yes, I knew that it would end, they are very open; when you go for your initial consultation, they will say to you listen, this study is [only for] so long” (PB002-PRT-001). Although the participants knew there would be no access, they were disappointed in the end. Nonetheless, some participants expressed appreciation for the period during which they received trial treatment, noting clear health benefits: “ I am very grateful that there is no damage to my joints and that is a huge advantage for me ” (PR006-PRT013). Ensuring effective handover Once the trial was completed, the participants were referred to routine care through site-specific handover processes. The participants also confirmed that they were sent back to the clinic with letters to take to their HCPs. Investigators implemented a process to ease transition that included “ Make appointments at the clinic ” (PB005); providing “ Study completion lette r” (PR006); and “ refer… with motivation…, increasing treatment doses or changing treatment ” (PR005). The investigators also demonstrated the need to make such handovers seamless for participants, given their impact if not well planned. “ When the end was approached, the participants became anxious ” (PR001). Additionally, the investigators remained available to support the participants after handover, as seconded by participants. “ They phoned me once to hear how it’s going..., But as I said, they said to me that if I’ve got any problems, I can contact them anytime, even if it’s two or three years later ” (PR006-PRT011). The participants corroborated the investigators and confirmed that letters were given; however, some HCPs stated that they did not receive letters and relied on verbal communication from the participants, as articulated by HCP006_BP002: “ Sometimes the patient might be able to tell me ”. Practices varied according to site, and some investigators communicated directly with the HCPs: “They’ll email me a letter, ask me to make a follow-up appointment for this patient who’s no longer in their study” (HCP003_PB006). Investigators defended their process and shared their experiences, noting that some HCPs were unreceptive to letters. “ We had some unfortunate instances, a few years ago, where patients were told that the nurses don’t want to see letters from outside doctors ” (PR005). HCPs recommended that investigators provide detailed information, similar to that required and provided by HCPs when referring participants to the trial, sufficient to enable the investigator to assess participant eligibility. HCPs outline that the information includes the trial treatment, the trial treatment arm and doses, laboratory results, information on adverse events, and practical safety guidance (HCP006_PB001; HCP003_PB006; HCP005_PR001). “ The same communication should go the other way when the trial is completed, so it shouldn’t be a difficult thing. It’s one of the things that we can truly get right ” (HCP003_PB006). The information is intended to enable HCPs to better manage participants, particularly side effects. The HCP also noted that such practices are not new and already exist as SoC when participants are transferred from one care facility to another: “ The document transfer letters already exist … whether you’re moving from one province to the next or one hospital to another ” (HCP004_PB006). They also urged that communication should be at the Investigator-HCP level, not through the participant. I think it will be better for communication to be between the trial centre and the referring Dr” (HCP006_BP002). Conducting post-trial follow-up (PTFU) PTFU was considered desirable but was not implemented by any of the investigators or HCPs included in this study. It was described as a process that should include follow-up after handover and treatment changes. Some investigators emphasised the need to ensure that, after treatment changes, participants are monitored for stability: “ He has to be followed up… you have to keep him stable when getting back to his previous care ” (PR004). When the investigators were also routine HCPs, PTFU occurred naturally, though it was neither formalised nor documented. “ They will come back for the checkups anyway ” (PR008). As further alluded, “ Once we started, new agents will monitor them fairly regularly, similar to how we started the study, until they’re stable, and then they go back to the regular visits” (PR004). However, investigators who were not HCPs were unable to follow up with participants after handover, and no further action was taken. “Unfortunately, we don’t have the budget from our site, we refer” (PB006). This expression illustrates that follow-up was desirable; it points to structural rather than perceptual barriers, suggesting that, with targeted funding, follow-up could be feasible. The lack of protocol requirements and funding was a significant barrier: “ it all comes down to money ” (PB006); it was suggested that the sponsors should “ provide for a few more post-trial care visits ” (PR001). Opinions varied on who should bear responsibility for PTFU, whether investigators or HCPs. Currently, investigator involvement ends at handover, especially when the investigator is not responsible for HCPs: “... the treating physician actually has to take responsibility ” (PB002). The HCPs expressed discomfort with the current process, where investigators conclude their role at handover: “ We are finished now, and this patient is now handed back to you” (HCP006_BP002). This expression demonstrated that HCPs were dissatisfied with the process, although some welcomed the role of ensuring PTFU. “ I think that it would be wonderful for us to do a six-month, one-year, two-year follow-up in patients and see what’s happened to them ” (HCP002_PR006). Involvement of HCPs There was a clear gap regarding the roles of HCPs and investigators in ensuring CoC, “… whether that continuity means they return to the state hospitals… have a follow-up with me… or… go back to another rheumatologist ” (HCP002_PR006). Where investigators were responsible for routine care, CoC was seamless and inherent. These investigators maintained dual care throughout the trial, ensuring both trial-related visits and routine follow-ups were maintained. “ They are seen at the trial unit…, then they will keep their regular follow-up with me, like 6 months or annual follow - up at the office ” (PR011). Where investigators were not responsible for routine care and the trial was conducted outside routine care facilities, barriers to CoC were noted. In some of the trials, SoC was either stopped or continued, or provided by the sponsor: “ You’re not allowed to take any other cholesterol tablets …” (PB005-PRT005); “ you have to stay on it in conjunction with the trial medication ” (PR006-PRT013). Such occurrences led to diminished involvement of HCPs during the trial, because participants did not see the need to continue with routine care: “ It wouldn’t be mandatory for the patient to continue ” (HCP004_PB006). Furthermore, HCPs noted a communication gap on the part of the investigators. HCPs argued that dual care should be maintained throughout the trial, regardless of changes to SoC provision. “ It is very important that while they’re on a trial, they still need to go to the state doctor s; there is again that continuity from both sides throughout the trial ” (HCP002_PR006). The HCPs were dissatisfied with communication from the investigators during the trial, and cited that, it often occurred only when participants experienced adverse events they could not manage: “ Usually, just if things are going wrong… I don’t usually get letters to say things are going fantastic ” (HCP003_PB006). Participants from state facilities had no named HCPs, adding another barrier to involvement of HCP. To resolve those challenges, investigators have engaged “ the most senior person… running the unit ” (PR006). HCPs warned that weak engagement risked patients being “ lost in the system ” (HCP004_PB006). HCPs had three suggestions. First, the consent process should be improved to encourage participants to disclose details of their HCPs and to engage their HCPs from the start of the trial (HCP004_PB006). However, this process is limited by GCP guidelines, which require participant consent before investigators contact HCPs: “_ It depends on whether the patient wants us to share certain information _” (PB003). Second, the HCP suggested that a feedback system be implemented during the trial, with investigators sharing participant progress notes periodically with HCPs via participants. “Provide a document, "I want you to show this to your clinician". The clinician would also have a way to sign to acknowledge that all is within normal range or some kind of feedback tool between the places ” (HCP004_PB006). Third, the HCP suggested that to maintain continuity, the sponsor should fund the HCP involvement: “ A budget where whenever the patient sees the HCP, the HCP receives a consultation fee, and I mean, it encourages this concept of continuity of care ” (HCP004_PB006). Discussion We conducted this study to explore the processes used by investigators and HCPs to ensure post-trial care for participants and the impact of these processes on participants. Post-trial care processes were neither structured nor formalised, nor included in trial protocols as a requirement, nor resourced or funded. They were characterised by unclear role boundaries between investigators and HCPs. Investigators used study completion letters given to participants to provide to their HCPs, but the HCPs often disputed receiving them. Investigators also booked appointments for participants' subsequent post-trial visits at their treating facilities, where investigators were not responsible for routine care. Participants reported they could access post-trial care without difficulty, but the SoC was not consistently perceived as satisfactory. Stopping the trial intervention mainly affected participants with RA, while those with DM and CVD did not express any impact from discontinuing the intervention. There was also no follow-up after handover to routine HCP; therefore, investigators and HCPs could not be certain about the impact of post-trial care on participants. The investigators and HCPs demonstrated that the focus should shift from post-trial care to CoC. CoC has often been regarded as synonymous with post-trial care ( 18 , 28 , 43 , 44 , 51 ). However, our findings on CoC expand the focus beyond the post-trial phase to encompass the entire trial lifecycle, including practical actions at enrolment, procedures during the trial, and post-trial measures. These findings concur with those of Mwangi et al., who emphasised the importance of ongoing care. Mwangi acknowledges that trial care is time-limited and that participants and clinical trial stakeholders must understand its temporary nature, urging them to focus on ongoing care that continues beyond the trial intervention ( 42 ). CoC requires maintaining a level of quality care that matches the standards set during the trial, securing optimal treatment options for patients, and ensuring an effective handover to routine HCPs with sufficient and clear information to support ongoing patient management. Implementing PTFU and involving HCPs throughout the trial alongside investigators to supports coordinated, comprehensive care for participants. Maintaining a standard of quality care comparable to trial standards at trial exit and ensuring accessible treatment options. The participants successfully transitioned to routine care, but many reverted to less effective regimens and reported dissatisfaction due to a decline in quality of life. Despite reverting to less effective treatment, our study found that accessing routine care was not a challenge at trial exit, unlike other studies that reported that participants faced difficulties re-establishing care after the trial ( 1 , 13 , 15 , 33 ). Pre-existing or established care before the trial facilitated access, in contrast with findings from studies involving persons living with HIV who reported challenges in linkage to care post-trial ( 13 , 15 ). Although participants continued to access care after the trial, there was no guarantee that they would maintain the quality of life they reported during the trial. The participants demonstrated that treatment before and after the trial was often suboptimal, which aligns with the literature. In South Africa, there is reported reliance on first-line regimens for diabetes that persists despite poor control and inconsistent adherence to standard treatment guidelines (STG) ( 43 , 44 ). Furthermore, access to treatment in South Africa is hindered by delays in regulatory approvals and inclusion of treatments in STGs. The first Dipeptidyl Peptidase-4 (DPP-4) inhibitor, sitagliptin, was approved by the United States of America (USA) Food and Drug Administration (FDA) for the treatment of type 2 diabetes in 2006 ( 45 ). Following approval, DPP-4 inhibitors were included in the USA treatment guidelines and position documents ( 45 – 47 ). However, in South Africa, it was approved by the Medicines Control Council (MCC) (the predecessor to SAHPRA) in 2012 ( 48 ). The National Essential Medicines List Committee (NEMLC) formally approved their addition in March 2025, demonstrating the delays in South Africa ( 45 – 47 , 49 ) Additionally, sarilumab, an interleukin-6 (IL-6) receptor antagonist used to treat moderate to severe RA in adults, was approved by the USA FDA on May 22, 2017, based on phase 3 trials involving over 1,000 patients, including South African participants ( 49 ). Sarilumab was not registered or approved in South Africa for reasons unknown; however, other alternatives, Interleukin-6 (IL-6) inhibitors, such as tocilizumab (Actemra®), are available but unaffordable to most South Africans ( 50 , 32 , 52 ) The SAHPRA continued access guideline outlines the requirements for continued access to a beneficial trial intervention after the trial. It outlines conditions, such as only when there is no SoC and a minimal duration of four years ( 27 ). In our findings, participants had limited-duration PTA, transitioned back, and had access to the suboptimal SoC, as demonstrated in RA participants. Though the SAHPRA continued access guideline provides directives, it lacks a clear definition of what SoC entails, leading participants to return to sub-optimal treatments. Our findings demonstrate that the SAHPRA continued access guidelines do not address the limitations of SoC, medicine registration, affordability, or prioritisation of trial participants. These findings align with criticisms of the Declaration of Helsinki, which remains narrowly focused on the investigational product rather than including other alternatives ( 22 – 25 ). Earlier versions of the Declaration recognised extension of post-trial obligations to include “other appropriate care,” a phrase removed in later revisions, a change widely criticised and especially regrettable in the South African context ( 22 – 25 ). This narrow focus does not account for the complex realities highlighted in our study. Our findings, therefore, highlight a policy gap: existing guidelines, such as SAHPRA and the Declaration of Helsinki, do not safeguard against declines in treatment quality once participants transition to routine care. Ensuring effective handover to routine HCPs with adequate information Investigators have used several practical processes at trial closures, such as appointment bookings, issuing study completion letters, and providing continued support, which are widely reported as handover tools in the literature ( 13 , 32 , 51 ). However, their effectiveness was inconsistent because HCPs either did not receive letters or as noted by investigators, often did not accept external letters. Notably, Nxumalo also reported that HCPs refused to accept outside referral letters and that participants reported receiving incorrect treatment, demonstrating the ineffectiveness of such letters ( 13 ). Similarly, Nalubega reported limited success with letters ( 16 ). In contrast, other studies have shown that letters are useful when they are delivered by participants ( 33 ). These findings demonstrate that letters alone are unreliable unless supported by follow-up communication and accountability mechanisms between investigators and HCPs. The Declaration of Helsinki and other ethics frameworks (e.g., South African Ethics in Health Research, ICH GCP, South African GCP) largely remain silent on the mechanics of handover ( 52 – 54 ). CIOMS requires, at a minimum, that researchers connect participants who require ongoing care to suitable services ( 3 ), but none specify how this handover should occur. This study, therefore, provides operational insights; however, further input is needed on the effectiveness of handover processes. Conducting post-trial follow-up (PTFU) to confirm stability once participants initiate post-trial care Both investigators and HCPs recognised the importance of short-term PTFU to confirm participant stability after transitioning to routine care. However, no structured or funded mechanism was in place to support it. The lack of a defined budget and unclear role responsibilities meant that neither assumed ownership. This aligns with the literature advocating dedicated funding for PTFUs, such as in Nalubenga’s proposed facilitated transition model, which requires a follow-up period of up to 12 months after the trial ( 32 ). CIOMS, on the other hand, provides guidance requiring researchers to offer follow-up for a specified period and then transfer care to an appropriate provider ( 3 ). Enabling HCP involvement alongside investigators The role of HCPs in ensuring continuity of care was unclear. To improve clarity and ensure HCP involvement, the following was proposed: implementing transparent consent processes; providing structured HCP notification tools at enrolment; providing progress notes; and establishing relationships with the heads of facilities where no single HCP is present. Implementing a transparent consent process aligns with the Declaration of Helsinki, which states that post-trial obligations should be disclosed to participants during informed consent ( 9 ). SA GCP and ICH GCP outline the elements of informed consent, which do not include disclosing post-trial plans to participants, unlike the Declaration of Helsinki ( 18 , 55 ). Only at the clinical trial application stage does SAHPRA require the applicant to provide post-trial plans ( 56 ). Furthermore, the SA guidelines for continuity of care do not include a disclosure requirement to participants ( 27 ). SA GCPs suggest that, during ethics review, guidance on participants’ post-trial care should be provided ( 55 ). According to this study's results, the South African guidelines do not adequately ensure that participants are informed about post-trial plans in a transparent manner, indicating a need for improvement. Structured involvement of HCP is required to ensure clarity, and the study supports the investigator informing the HCP of the participant’s involvement in the trial. This aligns with ICH E6 (R3) ( 52 ); however, SA GCP has not yet been updated from (R2) to (R3) ( 55 ). The ICH GCP (R3) shifts the passive process from participants informing their HCPs to an investigator-led approach, in which the investigator is responsible for informing HCPs of participants’ involvement in the trial. However, the process is still reliant on participant agreement, which must be obtained before the investigator initiates communication with HCPs ( 18 , 57 ). Sharing progress notes and feedback ensures that HCPs continue to provide oversight to routine background care throughout the trial and do not detach from oversight; it also aligns with CIOMS (2016), which emphasises the importance of agreements between investigators and HCPs to manage coexisting conditions ( 3 ). Our data extend the CIOMS requirement by indicating that such engagements between investigators and HCPs should cover not only coexisting conditions but also the conditions under study. These findings resonate with those of Mwangi et al. (2024), who outlined the importance of communication between researchers and routine HCPs to prevent patient disengagement during the trial ( 33 ). Furthermore, recent advances in ICH GCP E6 (R3) confirm that other suitably qualified HCPs may be involved in the medical care of trial participants in accordance with their routine activities ( 18 ). In alignment with R3, our study offers practical procedures to sustain ongoing care and involve HCPs throughout the trial. Additionally, when no individual HCP is responsible for routine care, such as in public facilities, building relationships with department heads could help ensure continuity. This finding contributed to the issues observed and reported, where HCPs in public practice were not responsive to participants' letters and did not implement recommendations from investigators ( 13 ). Conclusion To our knowledge, this study is the first in sub-Saharan Africa to examine post-trial care for chronic conditions, extending beyond the predominantly HIV-focused literature. This study redefines post-trial care as a CoC concept. It also demonstrates that focusing on post-trial care does not sufficiently address the challenges. The CoC process includes practical, feasible, and fundable steps that start at enrolment and extend beyond the trial and trial intervention. We propose a minimum package that includes transparent disclosure of post-trial plans to participants, early engagement between investigators and HCPs, routine progress updates, a handover package managed by the investigator directed at the HCP, varied methods of provision of treatment options that uphold trial standards and prioritise participants’ well-being, and funded follow-up visits integrated into protocols with clearly defined responsibilities and resourcing at the investigator level that extend beyond the last visits. Implementing these steps will reduce unnecessary gaps at trial exits, better align with CIOMS and emerging ICH E6 (R3) guidelines, and prioritise participants’ well-being throughout and after the trial. Embedding these processes into protocols, contracts, and budgets can reduce longstanding dilemmas and sustain participants’ trial benefits. When treatments are proven effective, they should be registered promptly, and the Essential Medicines List (EML) STGs updated, as done in other countries. While high costs pose a challenge, mechanisms for access should be established, such as manufacturers lowering prices and the government approving and including these medicines on its list. Recommendations To address the trial dilemma, this study emphasises the need for guidelines that extend beyond the limited scope of the post-trial care; instead, it highlights the importance of establishing a practical, implementable, fundable, and auditable CoC process. Investigators and HCPs are called upon to translate the concept of CoC into a structured, actionable framework. This involves creating clear procedures and mechanisms to ensure that participants continue to receive appropriate care after a clinical trial concludes. Trial sponsors have a critical responsibility to ensure that the CoC process is followed by allocating resources for these activities. For regulators and research ethics committees, the findings provide valuable insights into essential elements that should be incorporated into trial protocols and/or detailed in post-trial care plans. The findings provide a basis for developing a CoC framework. Limitations The study involved participants, researchers, and HCPs from a limited geographical region in South Africa. Although the sample was small, the data collected were appropriate for the research aims and provided sufficient information to address the objectives ( 36 ). Sample adequacy was based on the quality and depth of the data, not just the number of participants ( 36 – 39 ). Interviews were conducted until no new information emerged and data saturation was achieved ( 40 ). This study included respondents from South Africa and did not include participants from other regions. While the findings may be relevant elsewhere, limited geographic coverage in South Africa may limit their broader applicability. The study also focused on CVD, DM, and RA and did not include other patient populations, diseases or other settings. Future research should expand sampling to include participants beyond South Africa and patients with diverse conditions. Although we did not formally evaluate the CoC framework, our study contributes to its development. The outcome will offer value to other researchers pursuing research in this subject. Abbreviations Abbreviation Description CIOMS Council For International Organisations of Medical Sciences CoC Continuity Of Care CVD Cardiovascular Disease DM Diabetes Mellitus DPP-4 Dipeptidyl Peptidase 4 EML Essential Medicine List FDA Food and Drug Administration GCP Good Clinical Practice HCF Healthcare Facility HCP Health Care Provider HIV Human Immunodeficiency Virus ICH International Council for Harmonisation IL-6 Interleukin-6 MCC Medicines Control Counsil NEMLC National Essential Medicines List Committee PB Public PR Private PTA Post-Trial Access PTFU Post-Trial Follow-Up RA Rheumatoid Arthritis SAHPRA South African Health Products Regulatory Authority SoC Standard of Care STG Standard Treatment Guidelines USA United State of America WMA World Medical Association Declarations Ethical approval and consent for participation The study received approval from the University of Stellenbosch (S20/03/078 (PhD)) and the University of the Free State (UFS-HSD2020/2072/2505-000). Written informed consent was obtained from all study participants. All participants consented to the use of anonymised data. Availability of data and materials The interview guides and interview transcripts used and/or analysed during the current study are available from the author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding The study was funded by Author 1 , who also received bursary support from the University of Stellenbosch. Authors' contributions NBM was responsible for the conception of the study, data acquisition and analysis, and drafting of the manuscript. ED and EA provided supervision and oversight throughout the study. All the authors read and approved the final manuscript. Acknowledgements The authors would like to thank all the participants in the study for sharing their experiences with us. We also extend our gratitude to the following investigators and healthcare professionals who contributed data to this paper: Professor Bridget Hodkinson, Head of Rheumatology, Department of Medicine, University of Cape Town and Groote Schuur Hospital; Associate Professor Riëtte du Toit, Head of Rheumatology, Division of Rheumatology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital; Dr. Mark Abelson and Annusca King; Dr. Hemant Makan, Specialist Physician and Diabetologist; Rhona Middle, Site Manager at Excellentis Clinical Trial Consultants; Major Cindi, Director of CRISMO; Dr. Essack Mitha, Principal Investigator at Newtown Clinical Research Centre; Dr. Shaifaili Krishnan Joshi, Dr. Gareth Tarr, and Liesl Segal, Rheumatologist at Winelands; Prof Lesley Burgess, of Treat Research’s Cardiology Unit; Dr. Soraya Cassimjee; Dr. Riaz Ahmed Garda of Cardiology Practice; Dr. MMDe Vries Basson, Contract Principal Investigator; Dr Tshegofatso Mabelane, About Allergy, Dr. Mohlamme Mathabathe, Dr Ngoananoka Portia Dintwe (Ratau) and Dr Sophie Mathijs from the University of Pretoria Clinical Research Unit. Author details 1 Khomanani Health Research and Wellness Centre, South Africa 2 Stellenbosch University, Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences, South Africa 3 Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Division of Clinical Sciences, University of Oxford, Oxford, United Kingdom References Nalubega S, Cox K, Mugerwa H, Evans C. Moving to Another World: Understanding the Impact of Clinical Trial Closure on Research Participants Living with HIV in Uganda. Journal of the Association of Nurses in AIDS Care. 2019 Sep 1;30(5): E96–108. MRCT. MRCT Center Post-Trial Responsibilities Toolkit [Internet]. 2017 Nov [cited 2025 Aug 15]. Available from: https://mrctcenter.org/wp-content/uploads/2023/04/2017-12-07-Post-Trial-Responsibilities-Toolkit-Version-1.1.pdf CIOMS. International ethical guidelines for health-related research involving humans [Internet]. CIOMS; 2016 [cited 2025 Oct 26]. 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Successful Discontinuation of the Placebo Arm and Provision of an Effective HIV Prevention Product After a Positive Interim Efficacy Result: The Partners PrEP Study Experience [Internet]. Vol. 66, J Acquir Immune Defic Syndr. 2014. Available from: http://www.gatesfoundation.org/ Lawton J, White D, Rankin D, Elliott J, Taylor C, Cooper C, et al. Staff experiences of closing out a clinical trial involving withdrawal of treatment: Qualitative study. Trials. 2017 Feb 7;18(1). Lawton J, Blackburn M, Rankin D, Werner C, Farrington C, Hovorka R, et al. Broadening the Debate About Post-trial Access to Medical Interventions: A Qualitative Study of Participant Experiences at the End of a Trial Investigating a Medical Device to Support Type 1 Diabetes Self-Management. AJOB Empir Bioeth. 2019 Apr 3;10(2):100–12. ClinicalTrials.gov. Internet. 2025 [cited 2025 Nov 22]. Search results for Phase III interventional studies with results, South Africa. 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Table Table 1: Characteristics and summary of all respondents Investigator Location Participant investigator -HCP relationship Participant Code HCP Code PR001 Private Investigator is HCP PR001-PRT002 PR001 PB002 Public Investigator not HCP PB002-PRT-001 HCP001_BP002 PB005 Public Investigator not HCP PB005-PRT003 _ PB005 Public Investigator not HCP PB005-PRT004 _ PB005 Public Investigator not HCP PB005-PRT005 _ PB005 Public Investigator not HCP PB005-PRT012 _ PR002 Private Investigator is HCP _ _ PR003 Private Investigator is HCP _ _ PB003 Public Investigator not HCP _ _ PR004 Private Investigator is HCP Pr004-PRT010 PR004 PR004 Private Investigator is HCP Pr004-PRT008 PR004 PR004 Private Investigator is HCP Pr004-PRT009 PR004 PR004 Private Investigator is HCP Pr004-PRT006 PR004 PR004 Private Investigator is HCP Pr004-PRT007 PR004 PR005 Private- Public Investigator not HCP _ _ PR006 Private Investigator is HCP Pr006-PRT013 HCP001_ PR006 PR006 Private Investigator is HCP Pr006-PRT014 HCP002_ PR006 PR006 Private Investigator is HCP Pr006-PRT011 HCP001_BP002 PR007 Private- Public Investigator not HCP _ _ PR008 Private Investigator is HCP _ _ PR009 Private Investigator is HCP _ _ PR010 Private- Public Investigator not HCP _ _ PR011 Private Investigator is HCP _ _ PB006 Public Investigator not HCP PB006-PRT015 HCP002_PB006 and HCP005_PR001 PB006 Public Investigator not HCP PB006-PRT016 HCP006_PB001 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9005712","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":617016225,"identity":"e8f3f084-5a26-4437-9aa4-8abdd74113d0","order_by":0,"name":"Nyeleti Babitjie Mthombeni","email":"data:image/png;base64,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","orcid":"","institution":"Khomanani Health Research and Wellness Centre","correspondingAuthor":true,"prefix":"","firstName":"Nyeleti","middleName":"Babitjie","lastName":"Mthombeni","suffix":""},{"id":617016226,"identity":"b5533b8e-a262-49cd-891f-789ec39eb5e6","order_by":1,"name":"Eric Decloedt","email":"","orcid":"","institution":"Stellenbosch University","correspondingAuthor":false,"prefix":"","firstName":"Eric","middleName":"","lastName":"Decloedt","suffix":""},{"id":617016227,"identity":"f29fedef-bbf9-4682-b6f4-967cc5af017b","order_by":2,"name":"Elizabeth Allen","email":"","orcid":"","institution":"Stellenbosch University","correspondingAuthor":false,"prefix":"","firstName":"Elizabeth","middleName":"","lastName":"Allen","suffix":""}],"badges":[],"createdAt":"2026-03-02 05:08:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9005712/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9005712/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106307302,"identity":"789f4464-32ba-45af-afd7-6bd0ac19c899","added_by":"auto","created_at":"2026-04-07 10:04:33","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":42001,"visible":true,"origin":"","legend":"\u003cp\u003eIllustration of sub-themes that make up continuity of care\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9005712/v1/0ddcc16135d54c06ee50d173.jpg"},{"id":108381125,"identity":"b33dbd14-7c69-45a4-9508-0d676d4dbf8c","added_by":"auto","created_at":"2026-05-04 04:55:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":502596,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9005712/v1/d827231c-6351-46b3-9dd9-9de2cd79650e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eContinuity of care: Perspectives of participants, investigators, and healthcare providers after trial completion in South Africa\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eThe enduring dilemma of managing trial participants after they complete a trial is one that researchers, trial sponsors, policymakers, regulators, and ethics committees have struggled with for decades. Various terms describe what happens after the trial, such as post-trial responsibilities, post-trial obligations, post-trial care (PTC), transition care, care after research, responsible transitioning post-trial provisions, and linkage to care (\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). All these terms aim to encapsulate what should happen to trial participants after the trial, especially those who need care to safeguard their health and well-being (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn general, the trial duration is short, often enrolling participants who are reliant on chronic treatment managed by their routine health care providers (HCPs). Once in the trial, investigators are responsible for management, often at facilities outside the routine health care structures of the participants (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). During the trial, routine standard of care (SoC) treatments may be replaced, switched, paused, or continued as per the trial design (\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Participants are therefore exposed to the intervention, which may include the experimental medicine or device, or a placebo (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). At the end of the trial, care may continue with the trial intervention or replaced by SoC provided by routine health care facilities (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). When post-trial provisions were not adequately planned, participants express emotional distress, such as sadness, anger, disappointment, anxiety, hopelessness, despair and abandonment (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Participants fear losing the quality of care gained during the trial and the possibility of receiving inferior SoC in non-research facilities (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Furthermore, the lack of planned post-trial provisions affects the trial team when they witness their participants' distress (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePost-trial provision processes encompass multiple activities, including planning for access to an effective and safe SoC intervention (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), facilitating participants' reintegration into care following the trial (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), Furthermore, it includes arranging alternative SoC interventions (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), providing adequate medical care for trial-related adverse events (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), and implementing post-trial follow-up (PTFU) to detect the long-term impact or hazards of the trial intervention (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In addition, if the intervention is proven to be beneficial, continuation of the investigational medication may be provided through post-trial access (PTA) (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eResearchers and pharmaceutical sponsors rely on international ethical guidelines, such as the World Medical Association (WMA) Declaration of Helsinki, to prepare for trial closure (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). However, these guidelines have been criticised for neglecting overall post-trial care (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR23 CR24\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). This is because they focus primarily on other aspects of trial conduct, such as recruitment, informed consent and (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) on PTA (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). It is therefore not surprising that this is echoed in national guidelines, such as the South African Health Products Regulatory Authority (SAHPRA) Continued Access guidelines, which also focus on PTA, with no consideration of the overall post-trial care (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDelivering post-trial care involves multiple stakeholders. The WMA Declaration of Helsinki (2013) names sponsors, researchers, and host-country governments as responsible parties (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). These guidelines exclude routine HCPs, although they are responsible for routine care. The Council for International Organisations of Medical Sciences (CIOMS) outlines ethical guidelines for health-related research involving humans, requiring researchers and sponsors to explain how care will be provided for other conditions but not defining how HCPs should be engaged (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Literature also focuses mainly on the role of HCPs as recruiters or potential investigators, not as role players in ongoing or post-trial care (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Yet the documented experiences of the trial participants highlights practical challenges faced when HCPs were not part of the research process. Some reported being mistreated or judged for participating in a clinical trial, leading them to discontinue treatment (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The latest International Council for Harmonisation (ICH) GCP E6 (R3) acknowledges that appropriately qualified HCPs may provide medical care during the trial period in line with local regulations (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough the effects of post-trial care are acknowledged, limited research addresses its impact on patients at the conclusion of clinical trials. There is sparse data on how these processes affect African participants with chronic conditions. As part of a larger study involving trial participants, we explored the experiences of investigators and HCPs in providing post-trial care and its impact on clinical trial participants receiving chronic treatment for diabetes mellitus (DM), rheumatoid arthritis (RA), and cardiovascular disease (CVD).\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eThe aim, design and setting of the study\u003c/h2\u003e \u003cp\u003eThe study examined how investigators and HCPs manage participants' care after the trial and how the processes impacted the participants. We employed a qualitative method to explore the perspectives of investigators, routine HCPs, and participants with chronic conditions (DM, RA, and CVD).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eWe conducted semi-structured interviews with 38 respondents: 36 virtually and 2 face-to-face, lasting 30\u0026ndash;60 minutes, between 2021 and 2023. All interviews were audio-recorded via Microsoft Teams\u0026reg; and transcribed verbatim using NVivo\u0026reg;; the transcripts were checked against the recordings for accuracy (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). The interview guides (available on request) were based on the research aims and relevant literature (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR33 CR34 CR35 CR36 CR37\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e) and included open-ended questions with prompts. As new insights were identified, the guides were updated. The participants were reimbursed for their time.\u003c/p\u003e\n\u003ch3\u003eStudy population and sampling\u003c/h3\u003e\n\u003cp\u003eThe sample comprised of phase III adult clinical trials in RA, DM, and CDV conducted in South Africa between 1 January 2018 and 31 December 2020. Seventy-five such trials were identified on ClinicalTrials.gov (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). From these 75, we identified the trial sites and investigators involved using TrialTrove\u0026reg; (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). A total of 20 trials and 142 investigators were identified. The trial staff assisted with recruiting 15 participants for the identified trials. The participants, in turn, identified their HCPs or health care facilities that provided treatment post-trial.\u003c/p\u003e\n\u003ch3\u003eSampling\u003c/h3\u003e\n\u003cp\u003eThe study used convenience sampling, and investigators who responded to the invitation were included. The researcher maintained a reflexive journal during the interviews, recording key insights and reflections that guided the evaluation of information power and saturation.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eThematic analysis followed Braun and Clarke\u0026rsquo;s framework (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). An inductive coding approach was used to identify and organise recurring patterns within the data. These patterns were grouped into overarching themes that reflected the meanings conveyed in participants\u0026rsquo; narratives. Verbatim quotations were used to illustrate and support each theme. Reflexive practices were applied through iterative debriefing sessions with coauthors, enhancing the credibility of the findings.\u003c/p\u003e \u003cp\u003eThe investigators are identified in this document by a five-digit code (e.g., PB005 or PR005). The PBs denote sites in public facilities, while the PRs denote sites in private facilities. Participants are identified by an 11-digit code (e.g., PB005\u0026ndash;PRT005) that links them to their investigator. The HCPs are identified by an 11-digit code (e.g., HCP004_PB006) that associates them with investigators.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eFifteen research sites across five South African provinces participated: the Western Cape [Cape Town (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), George (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)], Free State [Bloemfontein (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)], Gauteng [cities: Johannesburg (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) and Pretoria (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)], and Mpumalanga [Nelspruit (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)]. There were 38 respondents, including 17 research staff, 15 clinical trial participants, and 6 HCPs. The 17-site staff consisted of 11 medical doctors and 6 research nurses across the sites, referred to here as investigators. Eight sites were in private facilities, whilst 7 were in public facilities or recruited participants from public facilities. All investigators had more than 10 years of trial experience. The participant group consisted of 15 individuals, 12 females and 3 males, with a mean age of 60 years. Six reported that the investigator was their HCP, and 9 indicated consulting HCPs from different facilities. The HCP group consisted of 6 medical doctors, 2 of whom worked in private facilities providing routine healthcare and four from public or state-run facilities.\u003c/p\u003e \u003cp\u003eThe HCP and investigator narratives of post-trial care, which were equated with a process of continuity of care (CoC), with 5 sub-themes (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). First, after the trial, care should be equivalent to that during the trial. This sub-theme is described as continued satisfactory quality of care. Second, CoC depends on accessible treatment options. Third, a referral and information transfer process (a handover subtheme), and fourth, post-trial follow-up to ensure stability. The fifth subtheme is involvement of HCPs as outlined in the figure below.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eDefining Post-trial Care\u003c/h3\u003e\n\u003cp\u003eInvestigators and HCPs emphasised the complexity and the persistent neglect of end-of-trial processes. As PB002 stated, \u0026ldquo;\u003cem\u003eI think you are going into difficult territory, \u0026hellip;it [has] always been the area of trials which is not as well managed\u003c/em\u003e\u0026rdquo;. HCPs questioned the very label \u0026ldquo;post-trial care\u0026rdquo;, arguing that it cements a false boundary and fails to solve the real problem. Instead, they called for a model of CoC that follows the participant beyond trial exit: \u0026ldquo;\u003cem\u003eI think to label anything as post-trial care would result in the current situation continuing to happen\u0026hellip; [There] should be a continuation\u003c/em\u003e\u0026hellip;\u0026rdquo; (HCP004_PB006).\u003c/p\u003e \u003cp\u003eInvestigators echoed concerns about a lack of continuity, expressing, for example, \u0026ldquo;\u003cem\u003efalling in between the cracks\u003c/em\u003e\u0026rdquo; and \u0026ldquo;\u003cem\u003ejust left to their own devices\u003c/em\u003e\u0026rdquo; by (PR006) or \u003cem\u003e\u0026ldquo;dropping back like a hot potato\u003c/em\u003e\u0026rdquo; by (PB003), articulating their discontent. PB003 stressed the need for a defined mechanism to ensure continuity, whereas PR004 judged the absence of such a mechanism as \u0026ldquo;\u003cem\u003enot ethical and not responsible\u003c/em\u003e\u0026rdquo;.\u003c/p\u003e\n\u003ch3\u003eContinued satisfactory quality of care\u003c/h3\u003e\n\u003cp\u003eWhen the trial ended, the participants returned to routine SoC. As one participant noted, \u0026ldquo;\u003cb\u003e\u0026hellip;\u003c/b\u003e\u003cem\u003ethe trial ended\u0026hellip; I was referred to the clinic\u003c/em\u003e\u0026rdquo; (PB005-PRT004). HCPs echoed this: \u0026ldquo;\u003cem\u003eWe go back to what would have happened even before\u003c/em\u003e \u0026ldquo;(HCP005_PR001). An investigator also attested, \u0026ldquo;\u003cem\u003eProf returned them\u003c/em\u003e \u003cb\u003e\u0026hellip;\u003c/b\u003e\u0026rdquo; (PB005).\u003c/p\u003e \u003cp\u003eThe participants described a stark contrast between quality of life during the trial and after the trial: \u0026ldquo;\u003cem\u003eI didn\u0026rsquo;t get flare-ups\u0026hellip;I had eight years of absolute pleasure and joy\u003c/em\u003e\u0026rdquo; (PR006\u0026ndash;PRT013). As such, after trial discontinuation, some experienced a decrease in quality of life: \u0026ldquo;\u003cem\u003eI took the same treatment as before\u003c/em\u003e; \u003cem\u003eit took me a while for me to feel the pains again\u003c/em\u003e\u0026rdquo; (PB006-PRT016). HCPs described witnessing this return to pretrial conditions.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u0026ldquo;\u003cem\u003eTerrible, devastating, and not just with terrible pain and disability but with also just a hopelessness. \u0026hellip; it's such an emotional rollercoaster \u0026hellip; there's a drug that works and then suddenly It's been taken out from underneath you. It's terrible\u003c/em\u003e\u0026rdquo; (HCP003_PB006).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eInvestigators and HCPs described that satisfactory care requires transitioning to options suitable for the condition but could not confirm whether satisfactory care was achieved because there was no structured follow-up process. However, the HCPs also indicated that some participants deteriorated after switching to SoC: \u0026ldquo;\u003cem\u003eVery often when they come off the trials, they flare\u003c/em\u003e\u0026rdquo; (HCP003_ PB006), and there were consequences for patients who continued with suboptimal SoC: \u003cem\u003e\u0026ldquo;Generally, patients just live their lives with terrible, uncontrolled disease\u003c/em\u003e\u0026rdquo; (HCP003_ PB006).\u003c/p\u003e \u003cp\u003eInvestigators and HCPs suggested establishing a follow-up process to monitor participants after the trial, which is described in detail in subtheme four, PTFU.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eAccess to optimal treatment options\u003c/h2\u003e \u003cp\u003eAll participants were on SoC treatment before the trial, and the SoC was provided either by the state or medical aid. The SoC was often described as suboptimal, encouraging patients to enrol for trial participation: \u0026ldquo;\u003cem\u003eI was bedridden, \u0026hellip;. nothing seemed to help me, and somebody told me that I must try the trial centre\u003c/em\u003e\u0026rdquo;. (PR006-PRT011)\u003c/p\u003e \u003cp\u003eAfter the trial, some participants received limited-duration post-trial access (PTA). PTA was more readily available for RA patients, limited for DM patients, and uncommon for CVD participants.\u003c/p\u003e \u003cp\u003eEventually, all participants returned to the SoC, which depended on the treatment option available and accessible. Returning to SoC occurred to both private and state participants. Some participants were able to access other alternative treatments after upgrading their medical insurance coverage or motivation at state clinics.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e \u003cem\u003e\u0026ldquo;It might not be the exact same\u0026hellip;there are alternatives, they lead to the level of care that the patients have at the moment\u0026rdquo;\u003c/em\u003e (PR005).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eAt the end of the trial, some treatments were available in South Africa; however, they were not accessible to participants. Barriers to access also depended on whether the participant received care from the state or had medical insurance. Barriers to access in state facilities were specific treatment protocols predominantly informed by affordability. HCPs managing state patients reported following national-level standard treatment protocols. This treatment protocol did not regard trial participation as a priority for access: \u0026ldquo;\u003cem\u003eNot guaranteed\u0026hellip; we have to put them through the same process\u0026hellip; some might not fulfil the criteria\u003c/em\u003e\u0026rdquo; (HCP006_BP002).\u003c/p\u003e \u003cp\u003eAn additional barrier was the cost of medicines once marketed. As one investigator noted, \u0026ldquo;\u003cem\u003eIt became available a couple of months after the trial\u0026hellip; it was R10 000\u003c/em\u003e (579.61 USD) a \u003cem\u003emonth, and the medical aids do not pay for that; there is just no way of the patients having access to the medication post-trial\u003c/em\u003e\u0026rdquo; (PR008).\u003c/p\u003e \u003cp\u003eThe participants expressed dismay at the pricing of some of the medicines for which they contributed trial data, stating that only worthy people could afford the exorbitantly priced medicines: \u0026ldquo;W\u003cem\u003eho can pay R10,000\u003c/em\u003e (579.61 USD) \u003cem\u003e\u0026hellip; you must be \u0026lsquo;Harry Oppenheimer\u0026rsquo;\u003c/em\u003e, [South African billionaire]\u003cem\u003e\u0026rdquo;\u003c/em\u003e (PR006-PRT014). The participants recommended making medicines affordable, calling out the manufacturers to take initiative if they indeed cared, \u003cem\u003e\u0026ldquo;Nothing\u0026rsquo;s too expensive if you want to help right, you try by all means to give out the help\u0026rdquo; (PB006\u0026ndash;PRT016).\u003c/em\u003e\u003c/p\u003e \u003cp\u003eAnother barrier cited by investigators was state facilities not being able to provide SoC as per international treatment guidelines, as some medicines were not listed in South Africa's national essential medicines list and standard treatment guidelines, as expressed: \u0026ldquo;\u003cem\u003eDipeptidyl peptidase 4 (DPP-4) inhibitors have been available for 10 years \u0026hellip; yet these drugs aren\u0026rsquo;t available\u003c/em\u003e\u0026rdquo; (PR004).\u003c/p\u003e \u003cp\u003eHCPs and investigators implemented solutions to ensure access to treatment, such as motivating for alternatives at local Hospital Pharmacy and Therapeutics Committees or, in the private sector, participants upgraded their medical insurance: \u0026ldquo;\u003cem\u003eShe knew that she would be able to upgrade and then get a different biologic on her medical aid\u003c/em\u003e\u0026rdquo; (PR006). HCPs reported that persuasion and motivation could sometimes secure access to treatment: \u0026ldquo;\u003cem\u003eSometimes I have managed to persuade the state's pharmacy and therapeutics committee to give them another biologic and that I have been successful in a few cases\u003c/em\u003e\u0026rdquo; (HCP003_PB006). In the state sector, HCPs also noted that it was possible to adjust doses within the SoC to improve outcomes. Despite the barriers indicated, both HCPs and investigators emphasised their obligation to act in the best interest of patients: \u003cem\u003e\u0026ldquo;We just must do our best with the drugs we have\u003c/em\u003e\u0026rdquo; (HCP003_ PB006).\u003c/p\u003e \u003cp\u003eNonetheless, investigators and HCPs stressed that, before enrolment, participants were clearly informed that they might return to their previous SoC without continued access to trial treatments.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u0026ldquo;\u003cem\u003eThey also understood from the beginning, \u0026hellip; for three years, we explained \u0026hellip; there was no planning for more long-term access; they were all fine with it\u003c/em\u003e\u0026rdquo;. (PB005).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eHCPs corroborated this narrative, highlighting that careful counselling on risks, uncertainty, and the experimental nature of trials was provided to participants at referrals: \u0026ldquo;\u003cem\u003eIt is important for us to explain that it\u0026rsquo;s sort of experimenting. I talk to them carefully in advance\u003c/em\u003e\u0026rdquo; (HCP006_BP002). The participants also alluded to their knowledge that the trial was only short-term: \u0026ldquo;\u003cem\u003eYes, I knew that it would end, they are very open; when you go for your initial consultation, they will say to you listen, this study is [only for] so long\u0026rdquo;\u003c/em\u003e (PB002-PRT-001).\u003c/p\u003e \u003cp\u003eAlthough the participants knew there would be no access, they were disappointed in the end. Nonetheless, some participants expressed appreciation for the period during which they received trial treatment, noting clear health benefits: \u0026ldquo;\u003cem\u003eI am very grateful that there is no damage to my joints and that is a huge advantage for me\u003c/em\u003e\u0026rdquo; (PR006-PRT013).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eEnsuring effective handover\u003c/h2\u003e \u003cp\u003eOnce the trial was completed, the participants were referred to routine care through site-specific handover processes. The participants also confirmed that they were sent back to the clinic with letters to take to their HCPs. Investigators implemented a process to ease transition that included \u0026ldquo;\u003cem\u003eMake appointments at the clinic\u003c/em\u003e\u0026rdquo; (PB005); providing \u0026ldquo;\u003cem\u003eStudy completion lette\u003c/em\u003er\u0026rdquo; (PR006); and \u0026ldquo;\u003cem\u003erefer\u0026hellip; with motivation\u0026hellip;, increasing treatment doses or changing treatment\u003c/em\u003e\u0026rdquo; (PR005). The investigators also demonstrated the need to make such handovers seamless for participants, given their impact if not well planned. \u0026ldquo;\u003cem\u003eWhen the end was approached, the participants became anxious\u003c/em\u003e\u0026rdquo; (PR001). Additionally, the investigators remained available to support the participants after handover, as seconded by participants.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u0026ldquo;\u003cem\u003eThey phoned me once to hear how it\u0026rsquo;s going..., But as I said, they said to me that if I\u0026rsquo;ve got any problems, I can contact them anytime, even if it\u0026rsquo;s two or three years later\u003c/em\u003e\u0026rdquo; (PR006-PRT011).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eThe participants corroborated the investigators and confirmed that letters were given; however, some HCPs stated that they did not receive letters and relied on verbal communication from the participants, as articulated by HCP006_BP002: \u0026ldquo;\u003cem\u003eSometimes the patient might be able to tell me\u003c/em\u003e\u0026rdquo;.\u003c/p\u003e \u003cp\u003ePractices varied according to site, and some investigators communicated directly with the HCPs: \u003cem\u003e\u0026ldquo;They\u0026rsquo;ll email me a letter, ask me to make a follow-up appointment for this patient who\u0026rsquo;s no longer in their study\u0026rdquo;\u003c/em\u003e (HCP003_PB006). Investigators defended their process and shared their experiences, noting that some HCPs were unreceptive to letters.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u0026ldquo;\u003cem\u003eWe had some unfortunate instances, a few years ago, where patients were told that the nurses don\u0026rsquo;t want to see letters from outside doctors\u003c/em\u003e\u0026rdquo; (PR005).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eHCPs recommended that investigators provide detailed information, similar to that required and provided by HCPs when referring participants to the trial, sufficient to enable the investigator to assess participant eligibility. HCPs outline that the information includes the trial treatment, the trial treatment arm and doses, laboratory results, information on adverse events, and practical safety guidance (HCP006_PB001; HCP003_PB006; HCP005_PR001).\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u0026ldquo;\u003cem\u003eThe same communication should go the other way when the trial is completed, so it shouldn\u0026rsquo;t be a difficult thing. It\u0026rsquo;s one of the things that we can truly get right\u003c/em\u003e\u0026rdquo; (HCP003_PB006).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eThe information is intended to enable HCPs to better manage participants, particularly side effects. The HCP also noted that such practices are not new and already exist as SoC when participants are transferred from one care facility to another: \u0026ldquo;\u003cem\u003eThe document transfer letters already exist \u0026hellip; whether you\u0026rsquo;re moving from one province to the next or one hospital to another\u003c/em\u003e\u0026rdquo; (HCP004_PB006). They also urged that communication should be at the Investigator-HCP level, not through the participant. \u003cem\u003eI think it will be better for communication to be between the trial centre and the referring Dr\u0026rdquo;\u003c/em\u003e (HCP006_BP002).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eConducting post-trial follow-up (PTFU)\u003c/h2\u003e \u003cp\u003ePTFU was considered desirable but was not implemented by any of the investigators or HCPs included in this study. It was described as a process that should include follow-up after handover and treatment changes. Some investigators emphasised the need to ensure that, after treatment changes, participants are monitored for stability: \u0026ldquo;\u003cem\u003eHe has to be followed up\u0026hellip; you have to keep him stable when getting back to his previous care\u003c/em\u003e\u0026rdquo; (PR004).\u003c/p\u003e \u003cp\u003eWhen the investigators were also routine HCPs, PTFU occurred naturally, though it was neither formalised nor documented.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u0026ldquo;\u003cem\u003eThey will come back for the checkups anyway\u003c/em\u003e\u0026rdquo; (PR008). As further alluded, \u0026ldquo;\u003cem\u003eOnce we started, new agents will monitor them fairly regularly, similar to how we started the study, until they\u0026rsquo;re stable, and then they go back to the regular visits\u0026rdquo;\u003c/em\u003e (PR004).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eHowever, investigators who were not HCPs were unable to follow up with participants after handover, and no further action was taken. \u003cem\u003e\u0026ldquo;Unfortunately, we don\u0026rsquo;t have the budget from our site, we refer\u0026rdquo; (PB006).\u003c/em\u003e This expression illustrates that follow-up was desirable; it points to structural rather than perceptual barriers, suggesting that, with targeted funding, follow-up could be feasible.\u003c/p\u003e \u003cp\u003eThe lack of protocol requirements and funding was a significant barrier: \u0026ldquo;\u003cem\u003eit all comes down to money\u003c/em\u003e\u0026rdquo; (PB006); it was suggested that the sponsors should \u0026ldquo;\u003cem\u003eprovide for a few more post-trial care visits\u003c/em\u003e\u0026rdquo; (PR001). Opinions varied on who should bear responsibility for PTFU, whether investigators or HCPs. Currently, investigator involvement ends at handover, especially when the investigator is not responsible for HCPs: \u0026ldquo;... \u003cem\u003ethe treating physician actually has to take responsibility\u003c/em\u003e\u0026rdquo; (PB002). The HCPs expressed discomfort with the current process, where investigators conclude their role at handover: \u0026ldquo;\u003cem\u003eWe are finished now, and this patient is now handed back to you\u0026rdquo;\u003c/em\u003e (HCP006_BP002). This expression demonstrated that HCPs were dissatisfied with the process, although some welcomed the role of ensuring PTFU.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u0026ldquo;\u003cem\u003eI think that it would be wonderful for us to do a six-month, one-year, two-year follow-up in patients and see what\u0026rsquo;s happened to them\u003c/em\u003e\u0026rdquo; (HCP002_PR006).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eInvolvement of HCPs\u003c/h2\u003e \u003cp\u003eThere was a clear gap regarding the roles of HCPs and investigators in ensuring CoC, \u0026ldquo;\u0026hellip;\u003cem\u003ewhether that continuity means they return to the state hospitals\u0026hellip; have a follow-up with me\u0026hellip; or\u0026hellip; go back to another rheumatologist\u003c/em\u003e\u0026rdquo; (HCP002_PR006). Where investigators were responsible for routine care, CoC was seamless and inherent. These investigators maintained dual care throughout the trial, ensuring both trial-related visits and routine follow-ups were maintained.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u0026ldquo;\u003cem\u003eThey are seen at the trial unit\u0026hellip;, then they will keep their regular follow-up with me, like 6 months or annual follow\u003c/em\u003e-\u003cem\u003eup at the office\u003c/em\u003e\u0026rdquo; (PR011).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eWhere investigators were not responsible for routine care and the trial was conducted outside routine care facilities, barriers to CoC were noted. In some of the trials, SoC was either stopped or continued, or provided by the sponsor: \u0026ldquo;\u003cem\u003eYou\u0026rsquo;re not allowed to take any other cholesterol tablets\u003c/em\u003e\u0026hellip;\u0026rdquo; (PB005-PRT005); \u0026ldquo;\u003cem\u003eyou have to stay on it in conjunction with the trial medication\u003c/em\u003e\u0026rdquo; (PR006-PRT013).\u003c/p\u003e \u003cp\u003eSuch occurrences led to diminished involvement of HCPs during the trial, because participants did not see the need to continue with routine care: \u0026ldquo;\u003cem\u003eIt wouldn\u0026rsquo;t be mandatory for the patient to continue\u003c/em\u003e\u0026rdquo; (HCP004_PB006). Furthermore, HCPs noted a communication gap on the part of the investigators. HCPs argued that dual care should be maintained throughout the trial, regardless of changes to SoC provision.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u0026ldquo;\u003cem\u003eIt is very important that while they\u0026rsquo;re on a trial, they still need to go to the state doctor\u003c/em\u003es; \u003cem\u003ethere is again that continuity from both sides throughout the trial\u003c/em\u003e\u0026rdquo; (HCP002_PR006).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eThe HCPs were dissatisfied with communication from the investigators during the trial, and cited that, it often occurred only when participants experienced adverse events they could not manage: \u0026ldquo;\u003cem\u003eUsually, just if things are going wrong\u0026hellip; I don\u0026rsquo;t usually get letters to say things are going fantastic\u003c/em\u003e\u0026rdquo; (HCP003_PB006).\u003c/p\u003e \u003cp\u003eParticipants from state facilities had no named HCPs, adding another barrier to involvement of HCP. To resolve those challenges, investigators have engaged \u0026ldquo;\u003cem\u003ethe most senior person\u0026hellip; running the unit\u003c/em\u003e\u0026rdquo; (PR006). HCPs warned that weak engagement risked patients being \u0026ldquo;\u003cem\u003elost in the system\u003c/em\u003e\u0026rdquo; (HCP004_PB006). HCPs had three suggestions. First, the consent process should be improved to encourage participants to disclose details of their HCPs and to engage their HCPs from the start of the trial (HCP004_PB006). However, this process is limited by GCP guidelines, which require participant consent before investigators contact HCPs: \u0026ldquo;_\u003cem\u003eIt depends on whether the patient wants us to share certain information\u003c/em\u003e_\u0026rdquo; (PB003). Second, the HCP suggested that a feedback system be implemented during the trial, with investigators sharing participant progress notes periodically with HCPs via participants.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u003cem\u003e\u0026ldquo;Provide a document, \"I want you to show this to your clinician\". The clinician would also have a way to sign to acknowledge that all is within normal range or some kind of feedback tool between the places\u003c/em\u003e\u0026rdquo; (HCP004_PB006).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eThird, the HCP suggested that to maintain continuity, the sponsor should fund the HCP involvement: \u0026ldquo;\u003cem\u003eA budget where whenever the patient sees the HCP, the HCP receives a consultation fee, and I mean, it encourages this concept of continuity of care\u003c/em\u003e\u0026rdquo; (HCP004_PB006).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe conducted this study to explore the processes used by investigators and HCPs to ensure post-trial care for participants and the impact of these processes on participants. Post-trial care processes were neither structured nor formalised, nor included in trial protocols as a requirement, nor resourced or funded. They were characterised by unclear role boundaries between investigators and HCPs. Investigators used study completion letters given to participants to provide to their HCPs, but the HCPs often disputed receiving them. Investigators also booked appointments for participants' subsequent post-trial visits at their treating facilities, where investigators were not responsible for routine care. Participants reported they could access post-trial care without difficulty, but the SoC was not consistently perceived as satisfactory. Stopping the trial intervention mainly affected participants with RA, while those with DM and CVD did not express any impact from discontinuing the intervention. There was also no follow-up after handover to routine HCP; therefore, investigators and HCPs could not be certain about the impact of post-trial care on participants.\u003c/p\u003e \u003cp\u003eThe investigators and HCPs demonstrated that the focus should shift from post-trial care to CoC. CoC has often been regarded as synonymous with post-trial care (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e). However, our findings on CoC expand the focus beyond the post-trial phase to encompass the entire trial lifecycle, including practical actions at enrolment, procedures during the trial, and post-trial measures. These findings concur with those of Mwangi et al., who emphasised the importance of ongoing care. Mwangi acknowledges that trial care is time-limited and that participants and clinical trial stakeholders must understand its temporary nature, urging them to focus on ongoing care that continues beyond the trial intervention (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCoC requires maintaining a level of quality care that matches the standards set during the trial, securing optimal treatment options for patients, and ensuring an effective handover to routine HCPs with sufficient and clear information to support ongoing patient management. Implementing PTFU and involving HCPs throughout the trial alongside investigators to supports coordinated, comprehensive care for participants.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMaintaining a standard of quality care comparable to trial standards at trial exit and ensuring accessible treatment options.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe participants successfully transitioned to routine care, but many reverted to less effective regimens and reported dissatisfaction due to a decline in quality of life. Despite reverting to less effective treatment, our study found that accessing routine care was not a challenge at trial exit, unlike other studies that reported that participants faced difficulties re-establishing care after the trial (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Pre-existing or established care before the trial facilitated access, in contrast with findings from studies involving persons living with HIV who reported challenges in linkage to care post-trial (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough participants continued to access care after the trial, there was no guarantee that they would maintain the quality of life they reported during the trial. The participants demonstrated that treatment before and after the trial was often suboptimal, which aligns with the literature. In South Africa, there is reported reliance on first-line regimens for diabetes that persists despite poor control and inconsistent adherence to standard treatment guidelines (STG) (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore, access to treatment in South Africa is hindered by delays in regulatory approvals and inclusion of treatments in STGs. The first Dipeptidyl Peptidase-4 (DPP-4) inhibitor, sitagliptin, was approved by the United States of America (USA) Food and Drug Administration (FDA) for the treatment of type 2 diabetes in 2006 (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). Following approval, DPP-4 inhibitors were included in the USA treatment guidelines and position documents (\u003cspan additionalcitationids=\"CR46\" citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e). However, in South Africa, it was approved by the Medicines Control Council (MCC) (the predecessor to SAHPRA) in 2012 (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e). The National Essential Medicines List Committee (NEMLC) formally approved their addition in March 2025, demonstrating the delays in South Africa (\u003cspan additionalcitationids=\"CR46\" citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAdditionally, sarilumab, an interleukin-6 (IL-6) receptor antagonist used to treat moderate to severe RA in adults, was approved by the USA FDA on May 22, 2017, based on phase 3 trials involving over 1,000 patients, including South African participants (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e). Sarilumab was not registered or approved in South Africa for reasons unknown; however, other alternatives, Interleukin-6 (IL-6) inhibitors, such as tocilizumab (Actemra\u0026reg;), are available but unaffordable to most South Africans (\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e The SAHPRA continued access guideline outlines the requirements for continued access to a beneficial trial intervention after the trial. It outlines conditions, such as only when there is no SoC and a minimal duration of four years (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). In our findings, participants had limited-duration PTA, transitioned back, and had access to the suboptimal SoC, as demonstrated in RA participants. Though the SAHPRA continued access guideline provides directives, it lacks a clear definition of what SoC entails, leading participants to return to sub-optimal treatments. Our findings demonstrate that the SAHPRA continued access guidelines do not address the limitations of SoC, medicine registration, affordability, or prioritisation of trial participants. These findings align with criticisms of the Declaration of Helsinki, which remains narrowly focused on the investigational product rather than including other alternatives (\u003cspan additionalcitationids=\"CR23 CR24\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Earlier versions of the Declaration recognised extension of post-trial obligations to include \u0026ldquo;other appropriate care,\u0026rdquo; a phrase removed in later revisions, a change widely criticised and especially regrettable in the South African context (\u003cspan additionalcitationids=\"CR23 CR24\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). This narrow focus does not account for the complex realities highlighted in our study. Our findings, therefore, highlight a policy gap: existing guidelines, such as SAHPRA and the Declaration of Helsinki, do not safeguard against declines in treatment quality once participants transition to routine care.\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eEnsuring effective handover to routine HCPs with adequate information\u003c/h2\u003e \u003cp\u003eInvestigators have used several practical processes at trial closures, such as appointment bookings, issuing study completion letters, and providing continued support, which are widely reported as handover tools in the literature (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e). However, their effectiveness was inconsistent because HCPs either did not receive letters or as noted by investigators, often did not accept external letters. Notably, Nxumalo also reported that HCPs refused to accept outside referral letters and that participants reported receiving incorrect treatment, demonstrating the ineffectiveness of such letters (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Similarly, Nalubega reported limited success with letters (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In contrast, other studies have shown that letters are useful when they are delivered by participants (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). These findings demonstrate that letters alone are unreliable unless supported by follow-up communication and accountability mechanisms between investigators and HCPs.\u003c/p\u003e \u003cp\u003eThe Declaration of Helsinki and other ethics frameworks (e.g., South African Ethics in Health Research, ICH GCP, South African GCP) largely remain silent on the mechanics of handover (\u003cspan additionalcitationids=\"CR53\" citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e). CIOMS requires, at a minimum, that researchers connect participants who require ongoing care to suitable services (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), but none specify how this handover should occur. This study, therefore, provides operational insights; however, further input is needed on the effectiveness of handover processes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eConducting post-trial follow-up (PTFU) to confirm stability once participants initiate post-trial care\u003c/h2\u003e \u003cp\u003eBoth investigators and HCPs recognised the importance of short-term PTFU to confirm participant stability after transitioning to routine care. However, no structured or funded mechanism was in place to support it. The lack of a defined budget and unclear role responsibilities meant that neither assumed ownership. This aligns with the literature advocating dedicated funding for PTFUs, such as in Nalubenga\u0026rsquo;s proposed facilitated transition model, which requires a follow-up period of up to 12 months after the trial (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). CIOMS, on the other hand, provides guidance requiring researchers to offer follow-up for a specified period and then transfer care to an appropriate provider (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eEnabling HCP involvement alongside investigators\u003c/h2\u003e \u003cp\u003eThe role of HCPs in ensuring continuity of care was unclear. To improve clarity and ensure HCP involvement, the following was proposed: implementing transparent consent processes; providing structured HCP notification tools at enrolment; providing progress notes; and establishing relationships with the heads of facilities where no single HCP is present.\u003c/p\u003e \u003cp\u003eImplementing a transparent consent process aligns with the Declaration of Helsinki, which states that post-trial obligations should be disclosed to participants during informed consent (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). SA GCP and ICH GCP outline the elements of informed consent, which do not include disclosing post-trial plans to participants, unlike the Declaration of Helsinki (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e). Only at the clinical trial application stage does SAHPRA require the applicant to provide post-trial plans (\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e). Furthermore, the SA guidelines for continuity of care do not include a disclosure requirement to participants (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). SA GCPs suggest that, during ethics review, guidance on participants\u0026rsquo; post-trial care should be provided (\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e). According to this study's results, the South African guidelines do not adequately ensure that participants are informed about post-trial plans in a transparent manner, indicating a need for improvement.\u003c/p\u003e \u003cp\u003eStructured involvement of HCP is required to ensure clarity, and the study supports the investigator informing the HCP of the participant\u0026rsquo;s involvement in the trial. This aligns with ICH E6 (R3) (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e); however, SA GCP has not yet been updated from (R2) to (R3) (\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e). The ICH GCP (R3) shifts the passive process from participants informing their HCPs to an investigator-led approach, in which the investigator is responsible for informing HCPs of participants\u0026rsquo; involvement in the trial. However, the process is still reliant on participant agreement, which must be obtained before the investigator initiates communication with HCPs (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSharing progress notes and feedback ensures that HCPs continue to provide oversight to routine background care throughout the trial and do not detach from oversight; it also aligns with CIOMS (2016), which emphasises the importance of agreements between investigators and HCPs to manage coexisting conditions (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Our data extend the CIOMS requirement by indicating that such engagements between investigators and HCPs should cover not only coexisting conditions but also the conditions under study. These findings resonate with those of Mwangi et al. (2024), who outlined the importance of communication between researchers and routine HCPs to prevent patient disengagement during the trial (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Furthermore, recent advances in ICH GCP E6 (R3) confirm that other suitably qualified HCPs may be involved in the medical care of trial participants in accordance with their routine activities (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). In alignment with R3, our study offers practical procedures to sustain ongoing care and involve HCPs throughout the trial.\u003c/p\u003e \u003cp\u003eAdditionally, when no individual HCP is responsible for routine care, such as in public facilities, building relationships with department heads could help ensure continuity. This finding contributed to the issues observed and reported, where HCPs in public practice were not responsive to participants' letters and did not implement recommendations from investigators (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTo our knowledge, this study is the first in sub-Saharan Africa to examine post-trial care for chronic conditions, extending beyond the predominantly HIV-focused literature. This study redefines post-trial care as a CoC concept. It also demonstrates that focusing on post-trial care does not sufficiently address the challenges. The CoC process includes practical, feasible, and fundable steps that start at enrolment and extend beyond the trial and trial intervention.\u003c/p\u003e \u003cp\u003eWe propose a minimum package that includes transparent disclosure of post-trial plans to participants, early engagement between investigators and HCPs, routine progress updates, a handover package managed by the investigator directed at the HCP, varied methods of provision of treatment options that uphold trial standards and prioritise participants\u0026rsquo; well-being, and funded follow-up visits integrated into protocols with clearly defined responsibilities and resourcing at the investigator level that extend beyond the last visits. Implementing these steps will reduce unnecessary gaps at trial exits, better align with CIOMS and emerging ICH E6 (R3) guidelines, and prioritise participants\u0026rsquo; well-being throughout and after the trial.\u003c/p\u003e \u003cp\u003eEmbedding these processes into protocols, contracts, and budgets can reduce longstanding dilemmas and sustain participants\u0026rsquo; trial benefits. When treatments are proven effective, they should be registered promptly, and the Essential Medicines List (EML) STGs updated, as done in other countries. While high costs pose a challenge, mechanisms for access should be established, such as manufacturers lowering prices and the government approving and including these medicines on its list.\u003c/p\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eRecommendations\u003c/h2\u003e \u003cp\u003e To address the trial dilemma, this study emphasises the need for guidelines that extend beyond the limited scope of the post-trial care; instead, it highlights the importance of establishing a practical, implementable, fundable, and auditable CoC process.\u003c/p\u003e \u003cp\u003eInvestigators and HCPs are called upon to translate the concept of CoC into a structured, actionable framework. This involves creating clear procedures and mechanisms to ensure that participants continue to receive appropriate care after a clinical trial concludes. Trial sponsors have a critical responsibility to ensure that the CoC process is followed by allocating resources for these activities. For regulators and research ethics committees, the findings provide valuable insights into essential elements that should be incorporated into trial protocols and/or detailed in post-trial care plans. The findings provide a basis for developing a CoC framework.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eThe study involved participants, researchers, and HCPs from a limited geographical region in South Africa. Although the sample was small, the data collected were appropriate for the research aims and provided sufficient information to address the objectives\u003c/span\u003e (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSample adequacy was based on the quality and depth of the data, not just the number of participants\u003c/span\u003e (\u003cspan additionalcitationids=\"CR37 CR38\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eInterviews were conducted until no new information emerged and data saturation was achieved\u003c/span\u003e (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study included respondents from South Africa and did not include participants from other regions. While the findings may be relevant elsewhere, limited geographic coverage in South Africa may limit their broader applicability. The study also focused on CVD, DM, and RA and did not include other patient populations, diseases or other settings. Future research should expand sampling to include participants beyond South Africa and patients with diverse conditions. Although we did not formally evaluate the CoC framework, our study contributes to its development. The outcome will offer value to other researchers pursuing research in this subject.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"457\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eAbbreviation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eDescription\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eCIOMS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eCouncil For International Organisations of Medical Sciences\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eCoC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eContinuity Of Care\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eCVD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eCardiovascular Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eDM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eDiabetes Mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eDPP-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eDipeptidyl Peptidase 4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eEML\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eEssential Medicine List\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eFDA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eFood and Drug Administration\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eGCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eGood Clinical Practice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eHCF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eHealthcare Facility\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eHCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eHealth Care Provider\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eHIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eHuman Immunodeficiency Virus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eInternational Council for Harmonisation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eIL-6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eInterleukin-6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eMCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eMedicines Control Counsil\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eNEMLC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eNational Essential Medicines List Committee\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003ePB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003ePublic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003ePTA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003ePost-Trial Access\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003ePTFU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003ePost-Trial Follow-Up\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eRA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eRheumatoid Arthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eSAHPRA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eSouth African Health Products Regulatory Authority\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eSoC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eStandard of Care\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eSTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eStandard Treatment Guidelines\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eUnited State of America\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.2227%;\"\u003e\n \u003cp\u003eWMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68.7773%;\"\u003e\n \u003cp\u003eWorld Medical Association\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent for participation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study received approval from the University of Stellenbosch (S20/03/078 (PhD)) and the University of the Free State (UFS-HSD2020/2072/2505-000). Written informed consent was obtained from all study participants. All participants consented to the use of anonymised data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe interview guides and interview transcripts used and/or analysed during the current study are available from the author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was funded by Author \u003csup\u003e1\u003c/sup\u003e, who also received bursary support from the University of Stellenbosch.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNBM was responsible for the conception of the study, data acquisition and analysis, and drafting of the manuscript. ED and EA provided supervision and oversight throughout the study. All the authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the participants in the study for sharing their experiences with us. We also extend our gratitude to the following investigators and healthcare professionals who contributed data to this paper: Professor Bridget Hodkinson, Head of Rheumatology, Department of Medicine, University of Cape Town and Groote Schuur Hospital; Associate Professor Riëtte du Toit, Head of Rheumatology, Division of Rheumatology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital; Dr. Mark Abelson and Annusca King; Dr. Hemant Makan, Specialist Physician and Diabetologist; Rhona Middle, Site Manager at Excellentis Clinical Trial Consultants; Major Cindi, Director of CRISMO; Dr. Essack Mitha, Principal Investigator at Newtown Clinical Research Centre; Dr. Shaifaili Krishnan Joshi, Dr. Gareth Tarr, and Liesl Segal, Rheumatologist at Winelands; Prof Lesley Burgess, of Treat Research’s Cardiology Unit; Dr. Soraya Cassimjee; Dr. Riaz Ahmed Garda of Cardiology Practice; Dr. MMDe Vries Basson, Contract Principal Investigator;\u0026nbsp;Dr Tshegofatso Mabelane, About Allergy, Dr. Mohlamme Mathabathe, Dr Ngoananoka Portia Dintwe (Ratau) and Dr Sophie Mathijs from the University of Pretoria Clinical Research Unit.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u0026nbsp;\u003c/sup\u003eKhomanani Health Research and Wellness Centre, South Africa\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u0026nbsp;\u003c/sup\u003eStellenbosch University, Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences, South Africa\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3\u003c/sup\u003e Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Division of Clinical Sciences, University of Oxford, Oxford, United Kingdom\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNalubega S, Cox K, Mugerwa H, Evans C. Moving to Another World: Understanding the Impact of Clinical Trial Closure on Research Participants Living with HIV in Uganda. Journal of the Association of Nurses in AIDS Care. 2019 Sep 1;30(5): E96\u0026ndash;108. \u003c/li\u003e\n\u003cli\u003eMRCT. MRCT Center Post-Trial Responsibilities Toolkit [Internet]. 2017 Nov [cited 2025 Aug 15]. Available from: https://mrctcenter.org/wp-content/uploads/2023/04/2017-12-07-Post-Trial-Responsibilities-Toolkit-Version-1.1.pdf\u003c/li\u003e\n\u003cli\u003eCIOMS. International ethical guidelines for health-related research involving humans [Internet]. CIOMS; 2016 [cited 2025 Oct 26]. Available from: https://cioms.ch/publications/product/international-ethical-guidelines-for-health-related-research-involving-humans/\u003c/li\u003e\n\u003cli\u003eCho HL, Danis M, Grady C. The ethics of uninsured participants accessing healthcare in biomedical research: A literature review. Clinical Trials. 2018 Oct 1;15(5):509\u0026ndash;21. \u003c/li\u003e\n\u003cli\u003eIunes R, Uribe MV, Torres JB, Garcia MM, Alvares-Teodoro J, De Assis Acurcio F, et al. Who should pay for the continuity of post-trial health care treatments? Int J Equity Health. 2019 Jun 3;18(1). \u003c/li\u003e\n\u003cli\u003eSofaer N., Lewis P., Davies H. Care After Research: A Framework For NHS RECs [Internet]. 2012. Available from: www.ptaworkshop.wordpress.com\u003c/li\u003e\n\u003cli\u003eMastroleo I. Post-trial obligations in the Declaration of Helsinki 2013: classification, reconstruction and interpretation. Dev World Bioeth. 2016 Aug 1;16(2):80\u0026ndash;90. \u003c/li\u003e\n\u003cli\u003eSofaer N, Lewis P, Davies H. Forthcoming practical framework for ethics committees and researchers on post-trial access to the trial intervention and healthcare. Vol. 40, Journal of Medical Ethics. BMJ Publishing Group; 2014. p. 217\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eWorld Medical Association. WMA Declaration of Helsinki ethical principles for medical research involving human participants general principles. Helsinki; 2024 Oct. \u003c/li\u003e\n\u003cli\u003eSchoenenberger-Arnaiz JA, Solanilla-Puertolas M, Acer-Puig M, Gomez-Arbones J. Informing primary care physicians of patients\u0026rsquo; involvement in clinical trials carried out at a specialist care level. Open Access J Clin Trials. 2017 Jul 27;9:59\u0026ndash;64. \u003c/li\u003e\n\u003cli\u003eMedicines and Healthcare products Regulatory Agency. Guidance on using non-investigational medicinal products in a clinical trial. [Internet]. 2025 Jun. Available from: https://www.legislation.gov.uk/uksi/2004/1031/contents\u003c/li\u003e\n\u003cli\u003eNovartis. https://www.novartis.com/clinicaltrials/glossary-clinical-trial-terms. 2025. Glossary of Clinical Trial Terms. Available from: https://www.novartis.com/clinicaltrials/glossary-clinical-trial-terms\u003c/li\u003e\n\u003cli\u003eNxumalo ST, Harris B, Napoles L, Oladimeji KE, Lalla-Edward ST. Qualitative study exploring reintegration of clinical trial participants with HIV to public health services in Johannesburg, South Africa. BMJ Open. 2024 Nov 24;14(11). \u003c/li\u003e\n\u003cli\u003eMRCT. Center Post-Trial Responsibilities Framework Continued Access to Investigational Medicines. 2017. \u003c/li\u003e\n\u003cli\u003eNgwenya N, Iwuji C, Petersen N, Myeni N, Nxumalo S, Ngema U, et al. Investigation of post-trial access views among study participants and stakeholders using photovoice and semi structured interviews. J Med Ethics. 2021 Jun 25;48(10):712\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eNalubega S, Cox K, Mugerwa H, Evans C. Ethical and practical considerations in HIV drug trial closure: perspectives of research staff in Uganda [Internet]. 2020. Available from: http://medrxiv.org/lookup/doi/10.1101/2020.11.14.20231720\u003c/li\u003e\n\u003cli\u003eOdero I, Ondeng\u0026rsquo;e K, Mudhune V, Okola P, Oruko J, Otieno G, et al. Participant satisfaction with clinical trial experience and post-trial transitioning to HIV care in Kenya. Int J STD AIDS. 2019 Jan 1;30(1):12\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eICH GCP E6 (R3). International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use ICH Harmonised Guideline for Good Clinical Practice E6(R3). 2025 Jan. \u003c/li\u003e\n\u003cli\u003eLlewellyn-Bennett R, Bowman L, Bulbulia R. Post-trial follow-up methodology in large randomized controlled trials: A systematic review protocol. Syst Rev. 2016 Dec 15;5(1). \u003c/li\u003e\n\u003cli\u003eCho HL, Danis M, Grady C. Post-trial responsibilities beyond post-trial access. Vol. 391, The Lancet. Lancet Publishing Group; 2018. p. 1478\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eSchipper I. Post-Trial Access to Treatment: corporate best practices [Internet]. 2015 Feb. Available from: https://www.researchgate.net/publication/308033982\u003c/li\u003e\n\u003cli\u003eMalik AY, Foster C. The revised Declaration of Helsinki: cosmetic or real change? Vol. 109, Journal of the Royal Society of Medicine. SAGE Publications Ltd; 2016. p. 184\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eNdebele P. The declaration of Helsinki, 50 years later. Vol. 310, JAMA. American Medical Association; 2013. p. 2145\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eEmanuel EJ. Reconsidering the declaration of Helsinki. Vol. 381, The Lancet. Elsevier B.V.; 2013. p. 1532\u0026ndash;3. \u003c/li\u003e\n\u003cli\u003eMorris K. Revising the declaration of Helsinki. The Lancet. 2013 Jun 1;381(9881):1889\u0026ndash;90. \u003c/li\u003e\n\u003cli\u003eDecision Tree PTA, SOMO. \u003c/li\u003e\n\u003cli\u003eSAHPRA. Guideline for post clinical trial access (PTA)/ Continued Access. Pretoria; 2022 Aug. \u003c/li\u003e\n\u003cli\u003eShrestha B, Dunn L. The Declaration of Helsinki on Medical Research involving Human Subjects: A Review of Seventh Revision. J Nepal Health Res Counc. 2020 Jan 21;17(4):548\u0026ndash;52. \u003c/li\u003e\n\u003cli\u003eWorld Medical Association declaration of Helsinki: Ethical principles for medical research involving human subjects. Vol. 310, JAMA. American Medical Association; 2013. p. 2191\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eMahmud A, Zalay O, Springer A, Arts K, Eisenhauer E. Barriers to participation in clinical trials: A physician survey. Current Oncology. 2018 Apr 1;25(2):119\u0026ndash;25. \u003c/li\u003e\n\u003cli\u003eBylund CL, Weiss ES, Michaels M, Patel S, D\u0026rsquo;Agostino TA, Peterson EB, et al. Primary care physicians\u0026rsquo; attitudes and beliefs about cancer clinical trials. In: Clinical Trials. SAGE Publications Ltd; 2017. p. 518\u0026ndash;25. \u003c/li\u003e\n\u003cli\u003eNalubega S, Cox K, Mugerwa H, Evans C. Facilitated transition in HIV drug trial closure: A conceptual model for HIV post-trial care. PLoS One. 2021 Apr 1;16(4 April 2021). \u003c/li\u003e\n\u003cli\u003eMwangi R., Mshana E., Kaheguka D., Mmbaga R M. \u0026ldquo;After the research, it\u0026rsquo;s like we have closed the contract\u0026rdquo;: Exploring post-trial transition, patient-centred care, ethical considerations and healthcare perspectives. African Journal of Bioethics. 2024 Aug 2. \u003c/li\u003e\n\u003cli\u003eHaire BG. Ethics of medical care and clinical research: A qualitative study of principal investigators in biomedical HIV prevention research. J Med Ethics. 2013;39(4):231\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eBeesham I, Heffron R, Evans S, Baeten JM, Smit J, Beksinska M, et al. Exploring the Use of Oral Pre-exposure Prophylaxis (PrEP) Among Women from Durban, South Africa as Part of the HIV Prevention Package in a Clinical Trial. AIDS Behav. 2021 Apr 1;25(4):1112\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eNdase P, Celum C, Campbell J, Bukusi E, Kiarie J, Katabira E, et al. Successful Discontinuation of the Placebo Arm and Provision of an Effective HIV Prevention Product After a Positive Interim Efficacy Result: The Partners PrEP Study Experience [Internet]. Vol. 66, J Acquir Immune Defic Syndr. 2014. Available from: http://www.gatesfoundation.org/\u003c/li\u003e\n\u003cli\u003eLawton J, White D, Rankin D, Elliott J, Taylor C, Cooper C, et al. Staff experiences of closing out a clinical trial involving withdrawal of treatment: Qualitative study. Trials. 2017 Feb 7;18(1). \u003c/li\u003e\n\u003cli\u003eLawton J, Blackburn M, Rankin D, Werner C, Farrington C, Hovorka R, et al. Broadening the Debate About Post-trial Access to Medical Interventions: A Qualitative Study of Participant Experiences at the End of a Trial Investigating a Medical Device to Support Type 1 Diabetes Self-Management. AJOB Empir Bioeth. 2019 Apr 3;10(2):100\u0026ndash;12. \u003c/li\u003e\n\u003cli\u003eClinicalTrials.gov. Internet. 2025 [cited 2025 Nov 22]. Search results for Phase III interventional studies with results, South Africa. Available from: https://clinicaltrials.gov/search?locStr=South+Africa\u0026amp;country=ZA\u0026amp;start=_2020-12-31\u0026amp;studyComp=_2020-12-31\u0026amp;aggFilters=phase:3,results:with,studyType:int\u0026amp;viewType=Card\u0026amp;utm_source=chatgpt.com\u003c/li\u003e\n\u003cli\u003eCiteline. Citeline Trialtrove [Internet]. Citeline; 2025 [cited 2025 Oct 21]. Available from: https://www.citeline.com/en/products-services/clinical/trialtrove\u003c/li\u003e\n\u003cli\u003eBraun V, Clarke V. Using thematic analysis in psychology. \u003c/li\u003e\n\u003cli\u003eBraun V+ C V. Thematic Analysis: A Practical Guide. Amy Hamer, editor. Pasaa Paritat Journal. London: Sage; 2022. 1\u0026ndash;331 p. \u003c/li\u003e\n\u003cli\u003eKok A, Hariram A, Webb D, Amod A. Patterns of diabetes management in South Africa: baseline and 24-month data from the South African cohort of the DISCOVER study. Journal of Endocrinology, Metabolism and Diabetes of South Africa. 2021 May 4;26(2):60\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eNgassa Piotie P, Webb EM, Rheeder P. Suboptimal control and failure to intensify therapy for South Africans with type 2 diabetes: an audit of diabetes management at primary health care facilities. Journal of Endocrinology, Metabolism and Diabetes of South Africa. 2024 Jan 2;29(1):37\u0026ndash;42. \u003c/li\u003e\n\u003cli\u003eGallwitz B. Emerging DPP-4 inhibitors: Focus on linagliptin for type 2 diabetes. Vol. 6, Diabetes, Metabolic Syndrome and Obesity. Dove Medical Press Ltd; 2013. p. 1\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eGallwitz B. Clinical use of DPP-4 inhibitors. Vol. 10, Frontiers in Endocrinology. Frontiers Media S.A.; 2019. \u003c/li\u003e\n\u003cli\u003eAhr\u0026eacute;n B. DPP-4 inhibition and the path to clinical proof. Front Endocrinol (Lausanne). 2019;10(JUN). \u003c/li\u003e\n\u003cli\u003eMSD (Pty) Ltd. Januvia package insert. 2012 Sep. \u003c/li\u003e\n\u003cli\u003eSanofi. Evaluation of Sarilumab (SAR153191/REGN88) on Top of Methotrexate in Rheumatoid Arthritis Patients (RA-MOBILITY). 2017 Jun 28 [cited 2025 Nov 22]; Available from: https://clinicaltrials.gov/study/NCT01061736#study-overview\u003c/li\u003e\n\u003cli\u003eMedecines Sans Fronti\u0026egrave;res. Second most recommended drug for COVID-19, will remain unaffordable \u0026amp; inaccessible for many [Internet]. Available from: https://www.msf.org.za/news-and-resources/press-relea\u0026hellip;r%20and,diverse%20producers%20in%20these%20countries\u003c/li\u003e\n\u003cli\u003eDe Nardi AT, Santos LP, Oliveira NL, Pfeifer LO, Botton CE, Umpierre D. Perspectives of elderly trial participants with hypertension on modes of delivery of individual summary reports: Study within a trial protocol [Internet]. 2020. Available from: https://osf.io/vzmjs\u003c/li\u003e\n\u003cli\u003eICH GCP E6 (R3) Draft guidelines. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use ICH Harmonised Guideline on Good Clinical Practice (GCP) E6(R3). 2023. \u003c/li\u003e\n\u003cli\u003eNational Health Research Ethics Council. South African Ethics in Health Research: Principles, Processes and Structure 3rd ed. [Internet]. Pretoria: South Africa; 2024. Available from: https://www.health.gov.za/nhrec-guidelines/\u003c/li\u003e\n\u003cli\u003eDepartment of Health. South African Good Clinical Practice: Clinical Trials Guidelines [Internet]. Pretoria; 2020 [cited 2024 Aug 11]. Available from: https://www.sahpra.org.za/wp-content/uploads/2021/06/SA-GCP-2020_Final.pdf\u003c/li\u003e\n\u003cli\u003eDepartment of Health. South African Good Clinical Practice: Clinical Trial Guidelines (SA GCP). Pretoria; 2020. \u003c/li\u003e\n\u003cli\u003eSAHPRA. GLF-CEM-CT-01A_v8-Clinical-Trial-Application-Form-CTF1. SAHPRA; 2022. \u003c/li\u003e\n\u003cli\u003eICH GCP E6 (R2). International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Harmonised Guideline Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2). 2016. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1: Characteristics and summary of all respondents\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInvestigator\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Location\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParticipant investigator -HCP relationship\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParticipant Code\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHCP Code\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePR001-PRT002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003ePR001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePB002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePublic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator not HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePB002-PRT-001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003eHCP001_BP002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePB005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePublic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator not HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePB005-PRT003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePB005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePublic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator not HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePB005-PRT004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePB005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePublic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator not HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePB005-PRT005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePB005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePublic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator not HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePB005-PRT012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePB003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePublic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator not HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePr004-PRT010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003ePR004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePr004-PRT008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003ePR004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePr004-PRT009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003ePR004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePr004-PRT006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003ePR004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePr004-PRT007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003ePR004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate- Public\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator not HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePr006-PRT013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003eHCP001_ PR006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePr006-PRT014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003eHCP002_ PR006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePr006-PRT011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003eHCP001_BP002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate- Public\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator not HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate- Public\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator not HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePR011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator is HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePB006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePublic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator not HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePB006-PRT015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003eHCP002_PB006 and HCP005_PR001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14.2857%;\"\u003e\n \u003cp\u003ePB006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.18367%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.3265%;\"\u003e\n \u003cp\u003ePublic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 22.449%;\"\u003e\n \u003cp\u003eInvestigator not HCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 19.3878%;\"\u003e\n \u003cp\u003ePB006-PRT016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 18.3673%;\"\u003e\n \u003cp\u003eHCP006_PB001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Continuity of care, ongoing care, post-trial obligations, after care, linkage to care, post-trial access, investigator-healthcare provider, post-trial follow-up, post-trial healthcare","lastPublishedDoi":"10.21203/rs.3.rs-9005712/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9005712/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e Despite decades of updates to frameworks and guidelines for the conduct of clinical trials, what happens to participants when a trial ends remains a persistent ethical dilemma. This study evaluated the views of investigators, healthcare providers (HCPs), and participants regarding post-trial care (PTC) for participants on chronic treatment after trial completion.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eThis study involved 38 interviews with 17 investigators, 15 trial participants and six HCPs from 15 trial sites in South Africa. Six of the investigators were also HCPs to the participants, and seven sites were in state or public facilities.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePost-trial care was unstructured, informal, and not included in trial protocols or budgets. The roles of investigators and HCPs were unclear. Study completion letters intended for HCPs were not received, and investigators arranged follow-up appointments at facilities where they had no ongoing responsibility. Participants continued with their pretrial standard of care (SoC) without the beneficial trial interventions. Discontinuing the intervention mainly affected those with Rheumatoid Arthritis (RA). Without post-trial follow-up (PTFU), the effective implementation of post-trial care for participants is unknown, and no quality of care or stability of treatment could be confirmed after switching treatment and returning to the pre-trial SoC. Investigators and HCPs disputed the concept of post-trial care and supported continuity of care (CoC). CoC was seen as a shared responsibility between investigators and HCPs and dependent on five interrelated processes: first, continued satisfactory quality of care comparable to trial standards at trial exit; second, access to optimal treatment options; third, ensuring effective handover to routine HCPs with adequate information, forth, conducting PTFU ensure stability once participants initiate post-trial care and last, involvement of HCP.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur findings propose reframing post-trial care as CoC by expanding the focus beyond the post-trial phase to the entire lifecycle of a trial. By having the trial end in mind, CoC should already be implemented at enrolment and continued until trial conclusion.\u003c/p\u003e\u003ch2\u003eRecommendations:\u003c/h2\u003e \u003cp\u003eThis study calls on policymakers, sponsors, investigators, and regulators to move beyond a narrow focus on the post-trial phase, primarily aimed at providing access to trial interventions, and adopt a practical, implementable, fundable, and auditable CoC process.\u003c/p\u003e","manuscriptTitle":"Continuity of care: Perspectives of participants, investigators, and healthcare providers after trial completion in South Africa","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-07 10:04:29","doi":"10.21203/rs.3.rs-9005712/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"62a62550-0c5a-4cc1-aebd-7366420075d3","owner":[],"postedDate":"April 7th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-04T04:47:25+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T04:54:56+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-07 10:04:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9005712","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9005712","identity":"rs-9005712","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}