{"paper_id":"53c253c9-00d7-4c92-8f34-ffa5df5f8b56","body_text":"R E S E A R C H Open Access\nWomen’s experiences of medical treatment\nfor endometriosis and its impact on PRE-\nEMPT trial participation: a qualitative study\nElaine Denny 1* , Annalise Weckesser 1, Georgina Jones 2, Stavroula Bibila 3, Jane Daniels 4,\nSiladitya Bhattacharya 5 and on behalf of the PRE-EMPT team\nAbstract\nBackground: Endometriosis is a common cause of chronic pelvic pain which can relapse after surgery, yet little\nresearch has been conducted on women ’s experience of medical treatments for prevention of recurrence and the\ninfluence of this on participation in clinical trials.\nMethods: This study explored women ’s past experiences with medical treatments for endometriosis symptoms and\nthe impact this has on their motivation to enter the pilot phase of a post-conservative surgery clinical trial, PRE-EMPT:\nPreventing Recurrence of Endometriosis by Means of long acting Progestogen Therapy. Qualitative methodology was\nadopted, involving semi-structured interviews in three UK cities, and one focus group was used to collect data from\nwomen with a diagnosis of endometriosis participating in the PRE-EMPT trial.\nResults: Ten women were interviewed individually and four took part in the focus group discussion. Women ’s\nwillingness to enter the PRE-EMPT trial was bound up with their previous experiences, present situation and future\nexpectations of medication, as well as the control offered by flexible randomisation which allows the option to reject\na particular treatment post-surgery.\nConclusion: Women were strongly influenced by previous experience and personal circumstances in their decision\nto enter the PRE-EMPT trial. This decision was facilitated by the ability to ‘opt out’ of the treatment arm(s) they found\nunacceptable. This element of choice offered patients a sense of control in the randomisation process and has important\nimplications for clinical trial design and recruitment.\nTrial registration: ISRCTN97865475. EUDRACT number 2013–001984-21.\nKeywords: Endometriosis, Treatment, Experiences, Qualitative research, Trial recruitment\nBackground\nEndometriosis is a chronic condition in women where\nendometrial tissue found outside the uterus produces an\ninflammatory response [1]. It has often been called the en-\nigmatic disease; its aetiology is not clearly understood [ 2,\n3], symptoms are extremely variable and there is only\nweak evidence underpinning many common medical\ntreatments [ 4–6]. While some women with laparoscopic\nevidence of pelvic endometriosis experience extreme pain,\nfatigue and infertility, others remain asymptomatic [ 5]a n d\nthe severity of symptoms is not correlated with the extent\nof disease [ 7]. Many qualitative studies have been under-\ntaken that seek to gain insight into the experience of\nendometriosis, but a search using the relevant databases\nfor qualitative studies on health and health care revealed\nno study where the primary purpose was to explore\nwomen’s experiences of medical treatments for endomet-\nriosis. However, this is an important issue for many symp-\ntomatic participants in endometriosis research. Women\ndescribe in graphic detail the extent of their pain and the\nimpact it has on their lives, often living with the condition\nfor many years before receiving a diagnosis [ 8–12]. They\nreport going through cycles of ineffective medical\n* Correspondence: elaine.denny@bcu.ac.uk\n1Centre for Social Care, Health and Related Research, Faculty of Health,\nEducation and Life Sciences, Birmingham City University, Westbourne Rd,\nEdgbaston, Birmingham B15 3TN, UK\nFull list of author information is available at the end of the article\n© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0\nInternational License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and\nreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to\nthe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver\n(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.\nDenny et al. Pilot and Feasibility Studies           (2018) 4:168 \nhttps://doi.org/10.1186/s40814-018-0358-5\n\ntreatments [ 9, 12–14], often with unpleasant side effects\n[7, 10, 15, 16]. Many of these treatments are also\ncontra-indicated in women who wish to become pregnant.\nThe lack of effective treatments will sometimes lead\nwomen to abandon medical treatment altogether [ 8]o rt o\nseek self-management strategies through alternative and\ncomplementary therapy [17].\nLaparoscopic excision of endometriotic lesions is consid-\nered to be effective in pain outcomes, in comparison to\ndiagnostic surgery alone [18], but the evidence is weak and\nrisks of relapse and reoccurrence of symptoms are high\n[19]. Prevention of recurrence of pain symptoms following\nsurgery involves the use of agents which reduce circulating\nlevels of oestrogen, causing shrinkage of remaining endo-\nmetriotic deposits and prevention of de novo lesions. A\nnumber of drugs, including long-acting reversible contra-\nceptives (LARCs) are in current use, but there is no\nconsensus as to which is most effective and cost effective\n(see latest trial protocol: https://njl-admin.nihr.ac.uk/docu-\nment/download/2011878). There is a need, therefore, to\nassess the clinical effectiveness of the available\npost-surgical treatment options in terms of controlling the\nrecurrence of endometriosis and improving quality of life.\nThe PRE-EMPT trial (see T able 1)a i m st oe v a l u a t et h e\nclinical effectiveness, cost effectiveness and acceptability of\nsuch treatment in women following conservative surgery\nfor endometriosis pain. The pilot phase of this trial [ 20]\nallowed flexible randomisation (i.e. the ability of partici-\npants to opt out of one or two treatments, as long as one\nLARC and one non-LARC was accepted) between four\npost-surgical options in preventing the recurrence of\nendometriosis:\n1) Combined oral contraceptive pill (COCP), containing\n30 μg ethinylestradiol and 150 μgl e v o n o r g e s t r e l\ntaken either continuously or cyclically;\n2) Levonorgestrel intrauterine system (LNG-IUS), as a\n20-μg per day formulation;\n3) Depot medroxyprogesterone acetate (DMPA), as a\n150-mg injection every 12 weeks;\n4) No medical treatment initiated post-laparoscopy.\nAs part of the pilot study for the PRE-EMPT trial, a\nstand-alone qualitative study was undertaken. Participa-\ntion in clinical trials, in particular randomised controlled\ntrials (RCTs), has always been problematic, with many\nfailing to recruit anticipated numbers [ 21]. Both quanti-\ntative and qualitative studies have considered why this is\nthe case, but their findings have had little effect on over-\nall recruitment [ 22]. This article will present the findings\nfrom the qualitative study within the PRE-EMPT clinical\ntrial which had the aim of exploring women ’s previous\nTable 1 The PRE-EMPT trial protocol summary\nDesign A randomised, pragmatic multicentre trial with integrated economic evaluation\nSetting Up to 40 NHS hospitals within the UK\nTarget population Women of reproductive age, who are undergoing laparoscopy to investigate whether their pelvic pain is due to endometriosis\nExclusion criteria Current infertility, immediate plans to conceive\nHealth technologies\nassessed\nThe main comparison is long-acting reversible contraception (LARC) versus combined oral contraceptive pill (COCP). Participants\ncan have a pre-randomisation choice of LARC (or alternatively one will be randomly allocated):\ni) Levonorgestrel-releasing intra-uterine system (LNG-IUS) (fitted by a gynaecologist) or\nii) 3 monthly depot medroxyprogesterone acetate (DMPA) injections (administered by the patient ’s gynaecologist or general\npractitioner); subcomparisons will be stratified by this choice\nOutcomes The primary outcome is the recurrence of symptoms as evaluated by the pain domain of the Endometriosis Health Profile –30\n(EHP-30) questionnaire at 36 months post-randomisation. The EHP-30 is a validated, responsive health-related quality of life\nmeasure for endometriosis. It will also be assessed prior to randomisation and at 6, 12 and 24 months.\nSecondary outcomes:\n All other symptom and quality of life (QoL) domains of the EHP-30\n Non-menstrual pelvic pain and dysmenorrhea measured by 0 –100 visual analogue (VAS) pain scale\n Fatigue, as measured by the Fatigue Severity Score\n Menstrual regularity\n Generic QoL (EQ-5D) and capabilities, as measure of wellbeing (ICE-CAP)\n Further diagnostic and therapeutic surgery for endometriosis (as a proxy for recurrence)\n Discontinuation rates of randomised treatment, with reasons for change, serious adverse events\n Cost per quality-adjusted life year (QALY) and cost per change in symptom score.\n An increased knowledge of issues identified as important by the participants regarding their treatment and its impact on their lives\nAnalysis The main comparison will be LARC vs COCP, with sub-comparisons of the groups where the intention is to treat with either\nLNG-IUS or DMPA if randomised to LARC. The primary outcome will be analysed using a linear regression model including a\nvariable for each treatment group and including baseline score and the minimisation factors as covariates. Effect sizes will be\npresented as point estimates and 95% confidence intervals. Standard statistical methods will be used for other outcomes.\nAll analysis will be by intention to treat.\nSample The study will have 90% power ( p = 0.05) to detect an 8-point difference in the main comparison assuming the standard deviation\nof the EHP-30 pain domain is 22 points. This will require 160 women per group, 320 in total. To account for 20% loss to follow-up,\nthis target has been inflated to 400 women in total\nDenny et al. Pilot and Feasibility Studies           (2018) 4:168 Page 2 of 10\n\nexperience of medical treatments for endometriosis\nsymptoms and the impact this has on their motivation\nto enter a clinical trial post conservative surgery.\nMethods\nDesign\nA qualitative approach to the study was considered ap-\npropriate as the aim of the study was to gain insight into\nwomen’s experiences and motivations and also to ex-\nplore issues of importance to them rather than to adhere\nstrictly to a script. Narratives are an important way for\npeople to explain disruptive events in their lives, and the\nuse of narrative interviews and a focus group in this\nstudy allowed women to reflect on living with endomet-\nriosis and to raise the issues that had greatest impact on\ntheir lives [ 23]. Three sites taking part in the PRE-EMPT\ntrial, Aberdeen Royal Infirmary, Birmingham Women ’s\nHospital and Edinburgh Royal Infirmary, all in the UK,\ntook part in the qualitative study, which comprised a\nfocus group discussion and individual interviews (see\nTable 2). The focus group and semi-structured interview\ntopic guides were informed by available literature on\nwomen’s experiences of medical treatments for endo-\nmetriosis symptoms, as well as the expertise of the\nPRE-EMPT Trial Management Group. As a means of es-\ntablishing rapport, at the beginning of interviews and\nthe focus group, some demographic data were collected.\nFavourable ethical approval for this study was obtained\nfrom the North of Scotland Research Ethics Committee\nand site-specific permission from the NHS Trusts of\neach of the hospitals involved.\nRecruitment\nPurposive sampling, that is sampling people who are\nrelevant to the research question [ 24], was undertaken.\nAll of the women recruited had been randomised in the\nPRE-EMPT trial and had given additional consent for\nthe stand-alone qualitative study following discussion\nwith the local research nurses. They were then\napproached by the researchers (AW and SB) and asked\nto take part in either the focus group (if from Aberdeen)\nor an individual interview. Formal written consent was\nobtained by the research nurses prior to interviews and\nthe focus group; researchers reiterated consent verbally\non the day of interview/focus group. The focus group\nand interviews were carried out by AW and SB, both ex-\nperienced qualitative researchers with an interest in\nwomen’s reproductive health. To foster open and honest\ndiscussions, the researchers explicitly stated that they\nwere university academics separate from hospitals in-\nvolved in the trial and reinforced the confidential and\nanonymous nature of women ’s participation. In appreci-\nation of their time, participants were given a £20 gift\nvoucher at the end of their interview or the focus group.\nData collection\nThe focus group discussion took place at Aberdeen\nRoyal infirmary. Initially, six women agreed to take part,\nbut only four attended. The focus group discussion\nelicited women ’s past experiences with the treatments\nincluded in the trial and examined their willingness to\naccept each treatment post-surgery and whether their\ninclusion in any of them would constitute a barrier to\ncontinuation within the study. Three women were inter-\nviewed in person (from Birmingham) and seven were\ninterviewed over the telephone (from Edinburgh and\nAberdeen) ( n = 10). Telephone interviews offered a flex-\nible means to include women from a wide geographical\nspread. Individual interviews allowed respondents to feel\nmore relaxed and able to address issues concerning their\nendometriosis treatment experiences that may have been\ntoo sensitive to discuss in a focus group setting [ 25].\nThe focus group and interviews were digitally audio re-\ncorded with consent and fully transcribed verbatim.\nWritten consent was obtained to use anonymised\nTable 2 Focus group and interview schedules\n1. Past medical treatment experiences\n Tell me about the types of medical treatments you have tried\n Prompts: Why did you try [names of treatments]? Who influenced\nyour decision? What were your expectations?\n Tell me about your experiences of …. [names of treatments]\n Prompts: Effectiveness/ineffectiveness of treatment? How long\neffective for? Side effects?\n2. Views on medical treatments offered in PRE-EMPT\nAfter undergoing surgery, there are four possible treatments —how do\nyou feel about:\n‘ The pill’\n‘ The coil’\n‘ Depo Provera’\n No treatment\n [For each treatment above] Prompt: (Un)Acceptable? Why? Past\nexperiences? Future hopes? Do you think the treatment would be\nmore effective post-surgery?\n Were there any treatments that you would not accept? Which? Why?\n3. Views on medical trials [General]\n What do you think about medical trials?\n What do you think about randomisation?\n Prompts: Understandings of randomisation/how treatment is\nallocated. Randomisation acceptable to you? Is the possibility of not\ngetting treatment acceptable?\n4. Views on participation in PRE-EMPT trial\n What do you think about the PRE-EMPT trial?\n Prompts: Hopes for the trial? Concerns about the trial?\n Why did you take part in the PRE-EMPT trial?\n Prompts: What did you hope to gain from participating? What were\nyour concerns about participating?\n What would be a barrier to you participating?\n Prompts: Personal factors? Time/travel costs? Trial factor? Concerns\nabout treatment availability/randomisation?\n Did you have a preference for which arm you would be randomised\nto? Why? Why not?\n Is this a worthy trial? Why? Why not?\n How do you feel about the length of the trial (3 years)?\n5. Concluding questions\n Is there anything we did not discuss that you would like to talk about?\n Do you have any questions for me?\nDenny et al. Pilot and Feasibility Studies           (2018) 4:168 Page 3 of 10\n\nextracts from the transcripts in publications. The focus\ngroup lasted 1 h and the interviews were 25 to 60 min\nin duration. All data were collected in January and\nFebruary 2015.\nAnalysis\nThematic analysis [ 24] was carried out by the qualitative\nresearch team, which consisted of two qualitative leads\n(ED and GJ) and two research assistants (AW and SB).\nAW and SB independently read the transcripts line by\nline, identifying emergent themes and created initial\ncodes. AW and SB brought these codes together to cre-\nate a coding framework, and AW coded the transcripts\nwith NVIVO 10. AW employed constant comparison, an\niterative method of analysis, searching for each themed\ncode throughout the entire data set (focus group, inter-\nview and telephone interview data), comparing all in-\nstances until no new themes were identified. Saturation\nwas deemed to have been reached when no new themes\nwere emerging from additional interview data. ED and\nGJ each independently read proportions of the transcrip-\ntions. The team jointly discussed and agreed upon com-\nmon patterns and broader themes from women ’s\nexperiences and perspectives on treatment acceptability.\nDissident views and areas of diversity among the team\nwere also considered and resolved. To establish the\ntrustworthiness [ 26] of the analysis, the four researchers\nindependently read the transcripts and compared find-\nings from the two parts of the data collection process.\nAlthough generalisation is not an aim of qualitative re-\nsearch, we were able to show consistency with the exist-\ning literature on women ’s experience of symptomatic\nendometriosis.\nResults\nIn reporting this study, standards for reporting qualita-\ntive research (SRQR) were adopted [ 27] (see Table 3).\nWomen participating in both the focus group and indi-\nvidual interviews shared their views and experiences of\nmedical treatments and their motivation for enrolling in\nthe PRE-EMPT trial. As no novel treatment was on\noffer, many women had previous experience of treat-\nments available as part of the RCT (either as endometri-\nosis treatment or for contraceptive purposes), which\nstrongly influenced their acceptability.\nSample\nThe ages of the 14 participating women varied from 19 to\n36 years, and experience of symptoms of endometriosis\nvaried from 2.5 to 16 years. There was a range of sympto-\nmology, treatment histories and allocated treatment\ngroups within the trial. A table detailing overall baseline\ncharacteristics of the sample is provided in T able 4.\nPersonal circumstances and past experiences\nMost women in both the FG and interviews spoke of\npast experiences of one or more of the interventions of-\nfered by the trial. Although some women had only re-\ncently received a diagnosis, nearly all had a long history\nof symptoms and had received at least one treatment.\nWomen described how endometriosis was affecting all\naspects of their lives, particularly work and personal\nrelationships.\nAnd then it was just getting unbearable, like difficult\nto walk. And then sex with my now ex-boyfriend was\nawful, which probably contributed to the end of the\nrelationship. (P7, interview).\nBut I think it was just more I was getting to the point\nthat I had to cancel nights out, days out, holidays and\neverything because the pain was just [unbearable]\n(P1, Focus Group).\nWomen graphically described the pain they experi-\nenced and the strategies that they would adopt to man-\nage everyday life.\nBecause you have the pain all the time, but then there ’s\nthat other pain, and you brace yourself - is the only way\nI can describe it. But I would literally start running\nthrough my work diary thinking, ‘Can I manage this\nday? Is there anything I can move around? Can I make\nit to the end of the week? ’ I would have real panic\nthinking,‘I’m not going to make it through today, I ’m\ngoing to have to cancel clinics. ’ I think that’s the bit that\ntook over my life. (P4, Focus Group).\nA number of women spoke of being dismissed and not\ntaken seriously in the past and of being misdiagnosed,\nwhich added to delays in receiving treatment. For them,\nthe trial was a sign that ‘someone was taking an interest ’\nin endometriosis, which encouraged them to participate.\nWomen had complex views in regard to whether\ntreatments they had used prior to surgery would be\nmore effective post-surgery. For example, some women\n(n = 3) had negative past experiences with both the\nCOCP and DMPA. While they would not accept the\nlatter post-surgery because of unpleasant side effects,\nthey were willing to accept the COCP as they believed\ni tm a yb em o r ee f f e c t i v ep o s t - s u r g e r y .‘Ik n o w[ t h ep i l l ]\ndidn’th e l pi nt h ep a s t ,b u t ,y o uk n o wi tm i g h tc h a n g e\nnow. Since I ’ve had an operation, it might help ’ (P5,\ninterview). Other women ( n = 3) did not believe a par-\nticular hormonal treatment would have more efficacy\npost-surgery as they had undergone surgeries before\nand found the treatment(s) equally ineffective or nega-\ntive after. ‘Id i d n’t really think I would have a different\nDenny et al. Pilot and Feasibility Studies           (2018) 4:168 Page 4 of 10\n\nTable 3 Standards for reporting qualitative research (SRQR) https://www.ncbi.nlm.nih.gov/pubmed/24979285\nPage/line\nno(s).\nTitle and abstract\nTitle - Concise description of the nature and topic of the study Identifying the study as qualitative or indicating the approach\n(e.g., ethnography, grounded theory) or data collection methods (e.g., interview, focus group) is recommended\nP1\nAbstract - Summary of key elements of the study using the abstract format of the intended publication; typically includes background,\npurpose, methods, results, and conclusions\nP1\nIntroduction\nProblem formulation - Description and significance of the problem/phenomenon studied; review of relevant theory and empirical\nwork; problem statement\nP1/30-P3/3\nPurpose or research question - Purpose of the study and specific objectives or questions P2/31-P3/3\nMethods\nQualitative approach and research paradigm - Qualitative approach (e.g., ethnography, grounded theory, case study, phenomenology,\nnarrative research) and guiding theory if appropriate; identifying the research paradigm (e.g., postpositivist, constructivist/ interpretivist)\nis also recommended; rationale**\nP3/6-P3/30\nP8/12-16\nResearcher characteristics and reflexivity - Researchers ’ characteristics that may influence the research, including personal attributes,\nqualifications/experience, relationship with participants, assumptions, and/or presuppositions; potential or actual interaction between\nresearchers’ characteristics and the research questions, approach, methods, results, and/or transferability\nP3/46-50\nContext - Setting/site and salient contextual factors; rationale** P3/55-70\nSampling strategy - How and why research participants, documents, or events were selected; criteria for deciding when no further\nsampling was necessary (e.g., sampling saturation); rationale**\nP3/34-54\nEthical issues pertaining to human subjects - Documentation of approval by an appropriate ethics review board and participant\nconsent, or explanation for lack thereof; other confidentiality and data security issues\nP3/26-29\nP10/34-38\nData collection methods - Types of data collected; details of data collection procedures including (as appropriate) start and stop\ndates of data collection and analysis, iterative process, triangulation of sources/methods, and modification of procedures in response\nto evolving study findings; rationale**\nP3/52-P4/4\nData collection instruments and technologies - Description of instruments (e.g., interview guides, questionnaires) and devices\n(e.g., audio recorders) used for data collection; if/how the instrument(s) changed over the course of the study\nP3/69-P4/4\nP 3 Table 2\nUnits of study - Number and relevant characteristics of participants, documents, or events included in the study; level of participation\n(could be reported in results)\nP4/44-49\nP3 Table 4\nData processing - Methods for processing data prior to and during analysis, including transcription, data entry, data management\nand security, verification of data integrity, data coding, and anonymization/de-identification of excerpts\nP3/69-P4/4\nData analysis - Process by which inferences, themes, etc., were identified and developed, including the researchers involved in data\nanalysis; usually references a specific paradigm or approach; rationale**\nP4/6-32\nTechniques to enhance trustworthiness - Techniques to enhance trustworthiness and credibility of data analysis (e.g., member checking,\naudit trail, triangulation); rationale**\nP4/24-31\nResults/findings\nSynthesis and interpretation - Main findings (e.g., interpretations, inferences, and themes); might include development of a theory\nor model, or integration with prior research or theory\nP4/50-58\nP4/80-P6/4\nP6/12-P7/48\nP7/57-P8/10\nLinks to empirical data - Evidence (e.g., quotes, field notes, text excerpts, photographs) to substantiate analytic findings P4/60-P7/88\nDiscussion\nIntegration with prior work, implications, transferability, and contribution(s) to the field - Short summary of main findings; explanation\nof how findings and conclusions connect to, support, elaborate on, or challenge conclusions of earlier scholarship; discussion of scope\nof application/generalizability; identification of unique contribution(s) to scholarship in a discipline or field\nP8/11-P9/73\nP9/100-P10/\n15\nLimitations - Trustworthiness and limitations of findings P9/117-30\nOther\nConflicts of interest - Potential sources of influence or perceived influence on study conduct and conclusions; how these were\nmanaged\nP10/58-60\nFunding - Sources of funding and other support; role of funders in data collection, interpretation, and reporting P10/20-23\n**The rationale should briefly discuss the justification for choosing that theory, approach, method or technique rather than other options available, the\nassumptions and limitations implicit in those choices, and how those choices influence study conclusions and transferability. As appropriate the rationale for\nseveral items might be discussed together\nDenny et al. Pilot and Feasibility Studies           (2018) 4:168 Page 5 of 10\n\nexperience [with hormonal treatments] because I ’ve\nhad the surgery before ’ (P7, interview).\nCurrent life circumstances, particularly in relation to\nreproduction, also influenced decision making regarding\nacceptability of treatment options.\nI do not want a child right now, so it ’s quite good that\nI am on the pill and that’s monitoring the endometriosis\nand that side of things as well. … So I think that ’ll vary\nfor everyone. I mean, I think, you know, depending on\nwhat age you are and what age you want to have\nchildren or where you are going in life, career-wise and\nthings as well, I think that will vary. (P8, interview).\nViews on individual treatment options\nThe majority of participants reported previous experi-\nence with one or more of the medications on offer in\nthe trial. No one option, which included the combined\nCOCP , LNG-IUS, DMPA, and no treatment, was found\nto be more or less acceptable by participants. This was\nsimilar to results of the clinical trial pilot study, which\nfound that no particular treatment combinations were\nchosen more than others [ 20].\nWhen women found the COCP an unacceptable treat-\nment option, this was due to experience of negative side\neffects in the past (including weight gain, mood swings\nand erratic periods) or because it had been ineffective in\nthe management of their symptoms. As one woman\nstates, ‘[The pill] didn ’t help at all. I was getting my pe-\nriods, like, quite a lot more than I should have. And it\ndidn’t help with the pain ’ (P4, interview). Those who\nfound the pill acceptable did so because of success with\nit as a treatment option in the past, the ease with which\nthey could both start and discontinue the pill, and a\nneed for contraception.\nSome women expressed ambivalence about the accept-\nability of COCP. For example, one participant found that\nit was not completely effective at controlling her endo-\nmetriosis symptoms in the past, but she was willing to\naccept it as a treatment option post-surgery as she\nregarded it as the best of the choices available. Further-\nmore, on the COCP , she states that ‘the pain still comes\nand goes, but the bleeding is a lot more under control. I\nfeel like now I control [my endometriosis] when I start\nand stop the pill as opposed to [endometriosis] control-\nling my life ’. (P8, interview). Other women who had lim-\nited success with the COCP in the past were willing to\naccept it as a treatment option because they would be\nprescribed a different contraceptive pill to the one(s)\npreviously taken or they believed that post surgery, the\npill may be more effective.\nWomen did not accept LNG-IUS as a treatment op-\ntion if they had previous negative side effect experiences\n(including discomfort, cramping, weight gain, increased\nbleeding, poor fittings and infections) or because of\nnegative experiences of friends and family members,\nwho had usually used it for contraceptive purposes. For\nexample, one woman rejected LNG-IUS as her mother\nhad become pregnant while using it. Those who found\nLNG-IUS acceptable did so because they had no previ-\nous experience with it and/or appreciated its conveni-\nence as a long-acting treatment, as once the coil was\ninserted, ‘you could forget about it ’ (P5, interview).\nTable 4 Baseline characteristics of sample\n(n = 14)\nAge, years Mean (SD) 27.9\n(5.7)\nEthnic group, n (%) White British 12 (86)\nBlack/Black British\nCaribbean\n1 (7)\nAsian/Asian British\nPakistani\n1 (7)\nMissing –\nParity, n (%) 0 12 (86)\n1 1 (7)\n2 1 (7)\nMissing –\nEmployment status, n (%) Full-time 10 (72)\nPart-time 1 (7)\nUnemployed 1 (7)\nStudent 2 (14)\nMissing –\nPrevious treatment experiences\nwith LNG-IUS, DMPA or COCP, n (%)\nAll 2 (14)\nLNG-IUS and COCP 1 (7)\nDMPA and COCP 5 (36)\nCOCP 6 (43)\nMissing –\nStage of endometriosis, n (%) I 5 (35)\nII 4 (29)\nIII 4 (29)\nIV 1 (7)\nMissing –\nNumber of previous laparoscopies,\nn (%)\n0 7 (50)\n1 5 (36)\n2 2 (14)\nMissing –\nExtent of excision as judged by\nsurgeon, n (%)\nComplete 11 (79)\nMissing –\nEHP-30 pain score at baseline Mean (SD) 59.7\n(9.7)\nMissing –\nDenny et al. Pilot and Feasibility Studies           (2018) 4:168 Page 6 of 10\n\nParticipants who would not accept DMPA as a treat-\nment option had found it ineffective in the management\nof their symptoms and/or had highly negative experi-\nences (including heavier/more frequent periods and mi-\ngraines) in the past. Two women found the repeat visits\nrequired to receive the injections inconvenient, as one\nstates ‘I work, I go to college, I ’m trying to have as much\nof a life as I can when I ’m not in pain...The thought of\ngoing to the doctor, it ’s quite far away from me as well …\nI just don ’t think it would be for me ’ (P5, interview).\nThose who accepted the DMPA as a treatment option\ndid so because it was a new option they had no previous\nexperience with and were therefore open to trying it.\nWomen who found randomisation to non-treatment\nunacceptable did so as they were concerned their\nendometriosis symptoms would return more quickly\npost-surgery or because they required hormonal contra-\nception. One woman enrolled in this arm of the trial\nexpressed concern that although happy with this option\nnow, her life circumstances may change and she could\nrequire a hormonal treatment for contraceptive purposes\non becoming sexually active. Those who found\nnon-treatment acceptable reported feeling they were\nwilling to let their body ‘have a break ’ (P6, interview)\nfrom hormonal treatments and to ‘let [their] body settle ’\n(P5, interview) after surgery and to assess the efficacy of\nthe surgery in relation to their symptoms.\nDecision making regarding treatments and views on\nrandomisation\nWomen found randomisation acceptable as they had an\nelement of choice over which treatment groups to be\nrandomised to (see Table 1).\nI obviously have tried pretty much every treatment for\nendometriosis before surgery. So that would obviously\nhave a big bearing on me. If something ’s not worked\nbefore, you know, you would as much as [pauses], like\nsay, if a doctor told me to take something just to try\nit, of course I would want to. But I think sometimes\nyou know your body better … especially if you ’ve had\n[the treatments] in the past. (P8, interview)\nMany women viewed randomisation as part of a ‘trial\nand error ’ process that is necessary to learn which\ntreatment options work best for individual women as\n‘every [treatment] works differently with everyone ’s\nbody’ (P4, interview). Half of the participants ( n = 7) re-\nported that without the option to opt out of a particular\ntreatment group (or groups), they would have declined\ntrial participation. Two women viewed randomisation\npositively as it relieved them from the burden of choos-\ning a treatment without adequate knowledge of the op-\ntions. Randomisation was seen as ‘quite a good thing ’,b y\none such participant as it ended the stress of deciding\nbetween multiple options and the confusion of ‘other\npeople telling you what to have, putting you off things,\nit’s better just the doctor saying, “That’s what you ’re hav-\ning.” Try it and that ’si t’ (P5, interview).\nExpectations of trial participation\nWomen chose to participate in the trial for reasons of\naltruism and self-interest. Participants expressed a desire\nto help others with endometriosis and to prevent them\n‘suffering’ from the same physical, emotional and health\nconsequences they had experienced. Many hoped the\ntrial would ‘raise awareness ’ and shorten pathways to\ndiagnosis, even though these were not aims of the trial.\n‘It took me a long time to be diagnosed … I wouldn ’t like\nother people to go through the wait and the pain that I\nwent through ’ (P6, interview). Women viewed the trial,\nand receiving medical treatment post-surgery, as a\nmeans of ‘gaining control ’ over their condition so that\nthey could ‘get their life back ’. Women also reported en-\nrolling in the trial out of ‘desperation’ and a willingness\nto ‘try anything ’ to manage the condition.\nOverwhelmingly, women found the 3-year length of\ntheir participation acceptable as this long study reflects\nthe chronic nature of endometriosis and the unpredict-\nable nature of symptoms that vary between women and\nover different stages of an individual ’s life. Further, they\nviewed the relatively long time period as a positive both\nfor themselves as individuals, as the efficacy of their\npost-surgery treatment would be monitored over the\ncourse of 3 years, as well as for the overall success of the\ntrial. Women felt it took time for their bodies to ‘get\nused to ’ hormonal treatments (or to the absence of hor-\nmonal treatment) and for negative side effects to sub-\nside. Some of those who had undergone previous\nlaparoscopic surgery for endometriosis felt that this\nalone reduced pain for 2 to 3 years. Thus, the trial\nlength was seen as advantageous to allow both for the\nefficacy of post-surgery treatments to be considered in\nlight of this ‘adjustment period ’ and for the decline in\nthe effectiveness of surgery to reduce pain over time.\nOnly one woman expressed a concern about the trial\nlength, stating that some participants may wish to be-\ncome pregnant during this time and would thus need to\nwithdraw from the study. Others indicated that they did\nnot view their participation as irrevocable, as a change\nin personal circumstances could precipitate a change in\ntreatment decisions.\nDiscussion\nThe aim of the study was to explore women ’s experience\nof medical treatments for endometriosis symptoms and\nthe impact this has on their motivation to enter a clin-\nical trial post conservative surgery. This trial aimed to\nDenny et al. Pilot and Feasibility Studies           (2018) 4:168 Page 7 of 10\n\ncompare existing treatments; no novel therapy was being\noffered and so previous and present experience of these\nwas particularly relevant. Our findings are consistent\nwith those of McCann et al. who conducted two\nmetasyntheses of studies which considered reasons for\nparticipation in phase 3 trials over the time periods\n1996–2005 and 2005 –2010. From these, they identified\nfour influences on the decision to enter an RCT [ 22]. In\nthe first study, (1996 –2005) personal circumstances\naround the time of recruitment to the study, views of\nthe trial treatment interventions, views of the trial pro-\ncesses and procedures, and weighing up benefit to self\nand others all influenced the decision making of pro-\nspective participants. From the findings of the second\nsynthesis (2005 –2005), McCann et al. argued that the\nfirst of these influences —where the participant was situ-\nated in terms of ‘health status, treatment juncture and\nperceptions of these at the time of recruitment ’—medi-\nated ‘the nature and salience of judgements ’ about the\nother three [ 22], page 238. In addition, we have demon-\nstrated how willingness to enter the PRE-EMPT trial\nwas bound up with previous experience and future\nexpectations of medication, as well as the control offered\nby the option to reject a particular treatment post-surgery.\nOverall, women did not report one post-surgery treatment\noption (including the no-treatment group) as more un-\nacceptable than any others. However, individually, women\nhad strong feelings about which treatments they found\nobjectionable based on their past negative experiences, or\nthose of their friends and family members, with that par-\nticular treatment. These strong treatment preferences\nshape participants’ views on randomisation, with half indi-\ncating they would have declined the trial if they had not\nbeen allowed the element of choice over which trial op-\ntions they would (and would not) be randomised to. Simi-\nlarly, research on women ’s participation in a trial\ncomparing surgical techniques for stress incontinence\nfound that non-participants were not averse to clinical tri-\nals per se but had strong preferences about specific as-\npects of treatment, in particular for a specific product and\na general anaesthetic [28].\nWhile women ’s previous experience of treatment influ-\nenced notions of acceptability of different treatments,\npoor experience did not necessarily equate with un-\nacceptability. Women ’s reasoning was complex, with\npast experience being weighed against future expectation\nof treatment in their decision making. Some women felt\nthat their changed circumstances (i.e. following surgery)\ncould lead them to experiencing a more positive result\nor changes to the medication itself (e.g. a different\nCOCP) may result in fewer side effects. That women\nwere prepared to retry medical treatments that may have\nbeen unsuccessful or had limited success in the past is a\nkey additional finding. This openness to receive\ntreatments that have previously been ineffective speaks\nto the ‘desperation’ some women reported in their on-\ngoing struggles to find effective interventions and desire\nto ‘try anything ’ to relieve their condition.\nQualitative thematic analysis highlighted that the com-\nplex rationales for which treatment options women\nfound acceptable need to be understood within the con-\ntext of their ongoing struggle to find long-term, effective\nmedical treatments that address their endometriosis\nsymptoms. Existing quantitative research shows only\nweak evidence of the effectiveness of many medical\ntreatments for managing endometriosis pain [ 4]. Add-\nitionally, a Cochrane review for endometriosis found\nonly low to moderate evidence for many medical treat-\nments, including suppression of menstrual cycles\nthrough GnRH analogues, LNG-IUS and Danazol, con-\nfirming the limited effectiveness of commonly prescribed\ninterventions [ 6] Although our study only asked women\nabout their experience of the treatment options in the\ntrial, the analysis highlights the patients ’ perspe ctive in\nnavigating this myriad of often ineffective medical treat-\nments available. It demonstrates that the complexity of\nwomen’s reasoning for wholly rejecting some treatment\noptions, while sometimes accepting others they also had\nprevious negative experiences with, is based on their on-\ngoing attempts with multiple medical treatments, each\nwith varied efficacy over time.\nPast qualitative research has shown that prior to diag-\nnosis, women report enduring their endometriosis symp-\ntoms for years (7 –11) and ‘suffer at a physical, emotional\nand social level ’ when they remain undiagnosed [ 9].\nWithin this body of literature, it has also been noted that\nwomen may be taking medications that are often used to\ntreat endometriosis, and this can mask symptoms of the\ncondition and contribute to delayed diagnosis [ 9, 10, 12].\nThese delays occur both at an individual patient level\nand a medical level [ 9, 14] and commonly feature the\nnormalisation of women ’s pain [ 9, 14]. Post-diagnosis,\nqualitative studies of endometriosis experiences show\nthat women report limited treatment success and recur-\nrent symptom relapses [ 9, 12–14], creating what has\nbeen termed a ‘medical merry-go-round ’ [29]. In relation\nto these findings, our analysis demonstrates that the\nwillingness of participants in this trial to try, and retry,\ntreatments out of ‘desperation’ likely stems from the\nhardships women face in delayed pathways to endomet-\nriosis diagnosis and the subsequent merry-go-round of\nmedical treatments. To what extent women ’s experi-\nences of the medical merry-go-round foster these feel-\nings of desperation, and shape their treatment-seeking\npractices, warrants further empirical investigation.\nWomen’s experiences of ongoing cycles of treatment ef-\nficacy and inefficacy are also reflected in findings on par-\nticipants’ views of the PRE-EMPT trial itself. Women\nDenny et al. Pilot and Feasibility Studies           (2018) 4:168 Page 8 of 10\n\nmade sense of the length of their trial participation\n(3 years) in terms of their own benefit as well as of the\nsuccess of the overall trial. Women ’s experience of the\nlong-term nature of endometriosis and the short- or\nmedium-term effect of treatments was seen as good jus-\ntification for a long follow-up period.\nThis study sheds light on the rationales underpinning\npatients’ decisions to enter clinical trials, which may be\nhelpful to future studies. The ability to recruit and retain\nsuitable participants to research, and in particular to ran-\ndomised trials, remains a major concern [ 21]. Qualitative\nmethods used early in the research process have been\nshown to improve recruitment, by addressing concerns\nthat are identified by participants in preparatory work, in\norder to increase the relevance and acceptability of partici-\npating in RCTs [ 30]. This study demonstrates that re-\nsearchers would benefit from considerations of the\ncomplex ways in which participants’ past histories, current\ncircumstances and future hopes with treatments offered\nin a trial comes to influence acceptability. Women in this\ntrial were open to retrying treatments with which they\nhad past negative or ambivalent experiences, especially in\nlight of changed circumstances (in this case, the potential\nfor the increased efficacy of treatments post laparoscopic\nsurgery). Such findings are useful for recruitment strat-\negies and can potentially inform how women are offered\nvarious treatment arm options. They also demonstrate\nhow the processes by which the research is conducted\nmay be designed to offer an element of choice and/or con-\ntrol to participants.\nResults from this qualitative study also highlight the im-\nportance of increased choice offered to patients through\nthe option to ‘opt out ’ of a particular treatment arm (or\narms). This element of choice offered patients an import-\nant sense of control in the randomisation process and is\nimportant to consider where there are strong preferences\namong potential trial recruits. Past qualitative research\nhas repeatedly shown that the issue of control is particu-\nlarly important to women living with endometriosis, as it\nhas been described as a disease that causes individuals to\nfeel a loss of control over their bodies and their lives [ 10,\n11, 17, 29, 31]. Furthermore, this research highlights that\nwomen view taking action through medical (as well as\ncomplementary) treatments as a means of reclaiming lost\ncontrol [ 11, 17]. Thus, our analysis demonstrates that\nwomen actively engaged in the management of their\nendometriosis could potentially find randomisation into a\ntrial without the ability to choose between treatment\narm(s) as unacceptable loss of control over their condi-\ntion. Knowledge of the importance of this element of\nchoice to patients can also be considered in the design the\nclinical trials and help improve overall recruitment. Flex-\nible trial designs have proved beneficial in other trial situa-\ntions, allowing multiple questions to be simultaneously\naddressed [ 32, 33]. However, flexibility is often provided\nto accommodate clinician preferences or practice, rather\nthan those of the participants.\nStrength and limitations\nAs far as we are aware, this is the first qualitative study\nto have experience of medical treatments for endometri-\nosis as its main focus. Using a qualitative research design\nhas enabled us to gain insight into this experience and\nhow women make sense of participation in a clinical\ntrial within this context. Using two research methods\nhas increased methodological rigour: however, a focus\ngroup of under six participants is below the generally\nagreed minimum [ 24]. The main limitation of the study\nis that participants were drawn only from women who\nhad agreed to be randomised to the PRE-EMPT trial.\nWomen who declined to participate, the two women\nwho did not attend the FG and women who are success-\nfully managed with medication may have different per-\nspectives on living with endometriosis. Research into\nwhy people with long-term conditions decline to take\npart in trials is limited but include not wanting disrup-\ntion to their lives, for example by extra clinic visits, or\ntheir state of health at the time of being approached\n[34], and the unknown of a clinical trial [ 35].\nPRE-EMPT trial participants are to be followed up for\n3 years, and during this time, women are likely to be on\nconception-preventing drugs. It is therefore probable that\nthis would be an additional reason women for whom fer-\ntility is a key issue would not be represented in the study.\nConclusion\nWomen in this study demonstrate complex pathways to\ndecision making regarding which treatments for endo-\nmetriosis they find acceptable, and this shapes their\nwillingness to enter a clinical trial for post-surgery treat-\nments to prevent symptom reoccurrence. In addition to\na mix of altruism and self-interest, women entered the\nPRE-EMPT trial because of the ability to ‘opt out’ of treat-\nment arm(s) they found unacceptable. This element of\nchoice offered patients a sense of control in the random-\nisation process and has important implications for clinical\ntrial design and recruitment. By not only including partici-\npants in the early stages of research design but also by\nallowing them to articulate their own decision-making\nprocesses in assessing treatment options and trial partici-\npation, researchers in many areas of health research may\noptimise recruitment and retention. In terms of endomet-\nriosis policy, it needs to be acknowledged that many\nwomen have been on a long journey, and their accumu-\nlated knowledge of what works, what does not and at what\npersonal cost needs to be included at the micro and macro\nlevels of policy making.\nDenny et al. Pilot and Feasibility Studies           (2018) 4:168 Page 9 of 10\n\nAcknowledgements\nThe authors would like to thank the women who shared their experiences of\nendometriosis and treatment, and the clinical staff who assisted with participant\nrecruitment.\nFunding\nThis study formed part of the HTA Project: 11/114/01 - PRE-EMPT: Preventing\nRecurrence of Endometriosis by Means of long acting Progestogen Therapy.\nAvailability of data and materials\nDue to the sensitive nature of the data generated and the possibility of\nidentification of individuals, datasets are not generally available. The anonymised\ndatasets used and/or analysed during the current qualitative study are available\nfrom the corresponding author on reasonable request.\nAuthors’ contributions\nSBH and JD designed the RCT. ED and GJ designed the qualitative study.\nSB conducted the literature review. AW and SB conducted the fieldwork.\nAW, SB, ED and GJ analysed the data. ED and AW wrote this article. All authors\ncontributed to the revision of this article. All authors read and approved the\nfinal manuscript.\nEthics approval and consent to participate\nEthical approval for this study was obtained from the North of Scotland Research\nEthics Committee 1 13/NS/0103 and site-specific assessment from NHS Trusts of\neach hospital involved in PRE-EMPT. Written consent was obtained from each\nparticipant prior to interview or focus group discussion.\nConsent for publication\nConsent for publication was obtained from women whose interview and\nfocus group data are quoted in the article.\nCompeting interests\nThe authors declare that they have no competing interests.\nPublisher’sN o t e\nSpringer Nature remains neutral with regard to jurisdictional claims in published\nmaps and institutional affiliations.\nAuthor details\n1Centre for Social Care, Health and Related Research, Faculty of Health,\nEducation and Life Sciences, Birmingham City University, Westbourne Rd,\nEdgbaston, Birmingham B15 3TN, UK. 2School of Social Sciences, Leeds\nBeckett University, Leeds LS1 9HE, UK. 3Coventry University Group, Armstrong\nSiddeley Building, Gosford St., Coventry CV1 5DL, UK. 4Nottingham Clinical\nTrials Unit, Queen ’s Medical Centre, C Floor, South Block, Nottingham NG7\n2UH, UK. 5Institute of Applied Health Sciences, School of Medicine, Polwarth\nBuilding, Foresterhill, Aberdeen AB25 2ZD, UK.\nReceived: 14 November 2017 Accepted: 15 October 2018\nReferences\n1. De Nardi P, Ferrrari S. Deep pelvic endometriosis: a multidisciplinary\napproach. Milan: Springer Science; 2011.\n2. Vinatier D, Cosson M, Dufour P. Is endometriosis an endometrial disease?\nEuropean Journal of Obstetrics and Gynecology. 2000;91(2):113 –25.\n3. Bricou A, Batt RE, Chapron C. Peritoneal fluid flow influences anatomical\ndistribution of endometriotic lesions: why Sampson seems to be right.\nEuropean Journal of Obstetrics & Gynecology and Reproductive Biology.\n2008;138(2):127–34.\n4. Lessey BA. Medical management of endometriosis and infertility. Fertil Steril.\n2000;73(6):1089–96.\n5. Dunselman G, et al. ESHRE guideline: management of women with\nendometriosis. Hum Reprod. 2014;29(3):400 –12.\n6. Brown J, Farquhar C. Endometriosis: an overview of Cochrane reviews. The\nCochrane database of systematic reviews. 2014;3. CD009590.\n7. Denny E, Mann CH. Endometriosis-associated dyspareunia: the impact on\nwomen’s lives. The Journal Of Family Planning And Reproductive Health\nCare / Faculty Of Family Planning & Reproductive Health Care, Royal\nCollege Of Obstetricians & Gynaecologists. 2007;33(3):189 –93.\n8. Jones GL, Jenkinson C, Kennedy S. The impact of endometriosis on quality\nof life: a qualitative analysis. J Psychosom Obstet Gynecol. 2004;(2):123 –33.\n9. Ballard K, Lawton K, Wright J. What ’s the delay? A qualitative study of\nwomen’s experience of reaching a diagnosis of endometriosis. Fertil Steril.\n2006;(5):1296–301.\n10. Denny E. Women ’s experience of endometriosis. J Adv Nurs. 2004;46(6):641–8.\n11. Gilmour JA, Huntington A, Wilson HV. The impact of endometriosis on work\nand social participation. Int J Nurs Pract. 2008;14(6):443 –8.\n12. Denny E. I never know from one day to another how I will feel: pain and\nuncertainty in women with endometriosis. Qual Health Res. 2009;19(7):985–95.\n13. Huntington A, Gilmour JA. A life shaped by pain: women and\nendometriosis. J Clin Nurs. 2005;14(9):1124 –32.\n14. Manderson L, Warren N, Markovic M. Circuit breaking: pathways of\ntreatment seeking for women with endometriosis in Australia. Qual Health\nRes. 2008;18(4):522–34.\n15. Strzempko Butt F, Chesla C. Relational patterns of couples living with\nchronic pelvic pain from endometriosis. Qual Health Res. 2007;17(5):571 –85.\n16. Seear K. The third shift: health, work and expertise among women with\nendometriosis. Health Sociol Rev. 2009;18(2):194 –206.\n17. Cox H, et al. Learning to take charge: women ’s experiences of living with\nendometriois. Complementary Therapies in Nursing & Midwifery. 2003;9(2):62–8.\n18. Jacobson TZ, et al. Laparoscopic surgery for pelvic pain associated with\nendometriosis. Cochrane Libr. 2009:CD001300 –0.\n19. Vercellini P, et al. Endometriosis. Drugs. 2009;69(6):649 –75.\n20. Middleton LJ, et al. Preventing recurrence of endometriosis by means of long-\nacting progestogen therapy (PRE-EMPT): report of an internal pilot, multi-arm,\nrandomised controlled trial incorporating flexible entry design and adaption of\ndesign based on feasibility of recruitment. Trials. 2017;18(1):121.\n21. Gul RB, Ali PA. Clinical trials: the challenge of recruitment and retention of\nparticipants. J Clin Nurs. 2010;19(1 –2):227–33.\n22. McCann SK, Campbell MK, Entwistle VA. Reasons for participating in randomised\ncontrolled trials: conditional altruism and considerations for self. Trials. 2010;11:31.\n23. Riessman CK. Narrative methods for the human sciences. Thousand Oaks,\nCalifornia: Sage; 2008.\n24. Bryman, A., Social research methods . 2008, Oxford University Press.\n25. Novick G. Is there a bias against telephone interviews in qualitative research?\nResearch in nursing & health. 2008;31(4):391–8.\n26. Noble H, Smith J. Issues of validity and reliability in qualitative research. Evid\nBased Nurs. 2015;18(2):34 –5.\n27. O ’Brien BC, Harris IB, Beckman TJ. Standards for reporting qualitative\nresearch: a synthesis of recommendations. Acad Med. 2014;89:1245 –51.\n28. Gopinath D, et al. Why don ’t women participate? A qualitative study on\nnon-participation in a surgical randomised controlled trial. Int Urogynecol J.\n2013;24(6):969–75.\n29. Cox H, et al. Focus group study of endometriosis: struggle, loss and the\nmedical merry-go-round. Int J Nurs Pract. 2003;9(1):2 –9.\n30. Audrey S. Qualitative research in evidence-based medicine: improving\ndecision-making and participation in randomized controlled trials of cancer\ntreatments. Palliat Med. 2011;25(8):758 –65.\n31. Jones G, et al. Development of an endometriosis quality-of-life instrument:\nthe endometriosis health Profile-30. Obstet Gynecol. 2001;98(2):258 –64.\n32. Gray R, et al. Long-term effectiveness of dopamine agonists and\nmonoamine oxidase B inhibitors compared with levodopa as initial\ntreatment for Parkinson ’s disease (PD MED): a large, open-label, pragmatic\nrandomised. LANCET. 2014;384(9949):1196 –205.\n33. Senapati A, et al. PROSPER: a randomised comparison of surgical treatments\nfor rectal prolapse. Color Dis. 2013;15(7):858 –68.\n34. Lowton K. Trials and tribulations: understanding motivations for clinical\nresearch participation amongst adults with cystic fibrosis. Soc Sci Med. 2005;\n61(8):1854–65.\n35. Canvin K, Jacoby A. Duty, desire or indifference? A qualitative study of\npatient decisions about recruitment to an epilepsy treatment trial. Trials.\n2006;7(1):32.\nDenny et al. Pilot and Feasibility Studies           (2018) 4:168 Page 10 of 10","source_license":"CC0","license_restricted":false}