A Qualitative Study Exploring Patient Global Impression of Disease Severity in Early Stages of Parkinson’s Disease.

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A Williams, Angela Stroupe, C del Rosario, C Umanzor-Figueroa, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4731346/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 Introduction Although Parkinson’s Disease is the second most common neurodegenerative disease, the lived experience of individuals with early-stage Parkinson’s has not received much attention. This study sought to understand how the spectrum of severity is described and perceived by this population using the Patient-Global Impressions of Severity scale. Additionally, early-stage Parkinson’s patients described what symptoms and quality of life impacts were most important to the early stages of the Parkinson’s experience. Methods In this study, 17 participants with early-stage Parkinson’s (1-2.5 on the modified Hoehn and Yahr scale) were interviewed about their experience with Parkinson’s as well as cognitively debriefed on the Patient Global Impressions of Severity scale. Analysis was performed using NVivo 13 a qualitative analysis software. Results Most participants reported tremors as their most bothersome symptom and the impact to their daily lives was most disruptive. Nearly every participant spoke about the emotional burden of their Parkinson’s diagnosis. Contemplating the future of their disease had a significant impact, which several said caused them to experience anxiety and/or depression. Participants were also able to describe the spectrum of severity for Parkinson’s and its quality of life impact, including severity levels they have not yet reached, using the global severity scale. Discussion This study highlights that even at the early stages of the disease, individuals living with Parkinson’s experience a wide range of symptoms and related quality of life impacts which shape their daily experience and contribute to perceptions of severity. Figures Figure 1 Figure 2 1 Introduction Parkinson’s Disease (Parkinson’s) is a neurodegenerative disorder caused by the loss of dopamine producing brain cells used to control the body’s movements. Affecting approximately 8.5 million people globally [ 2 ], Parkinson’s is the second most common neurological disorder. Early to late-stage Parkinson's is profiled as transitioning from stages 1 and 2 to stages 3–5 on the modified Hoehn and Yahr scale (mH&Y) [ 5 – 7 ]. Symptoms continue to worsen over a span of 20 years [ 8 ]. In Stage 1, mild symptoms often go unnoticed. In Stage 2, symptoms become increasingly noticeable on both sides of the body, and speech impacts begin to occur. Stage 3 is marked by imbalance and an increase in falls, and daily activities become more difficult. At Stage 4, patients often need a walking aid and assistance with tasks and are considered no longer fully independent. In Stage 5, patients are no longer mobile and often experience freezing and stumbling when they try to stand or move independently [ 9 ]. Although the impacts of Parkinson's are the subject of a large body of research, much less focus has been placed on how early-stage patients view their current disease and its severity, how they envision disease severity will progress and what impacts their disease progression will bring. Thus, the disease experience of patients at early stages of Parkinsons remains largely under-studied. Understanding the patient perception of severity may help manage common related impacts like anxiety and depression, as it has been shown that there is low agreement between clinician-reported severity on the mH&Y, the Clinical Global Impression of Severity scale (CGIS), and the Clinical Impression of Severity Index (CISI) measures in comparison to the Patient Global Impression of Severity (PGI-S)[ 14 ], a commonly used measure to assess severity in progressive diseases[ 15 , 16 ]. Löhle et al. [ 17 ] found that the PGI-S scale found agreement in scores only 35.1% of the time; confirming the importance of understanding disease severity from the patient's perspective. This study conducted qualitative interviews with patients at early stages of Parkinson's to ascertain how the spectrum of severity is described and perceived by this population using a patient-reported global measure of severity and to better understand the early-stage patients’ experiences by exploring what symptoms and Health Related Quality of Life (HRQoL) impacts were pivotal to them. 2 Methods 2.1 Interview Methodology The interview data was collected by experienced interviewers trained in capturing disease severity in early staged populations and who are experts at cognitively debriefing patient reported measures. The interviews lasted approximately 50 minutes and involved 2 phases. The first phase was a brief semi-structured discussion around the symptoms that led to participants’ diagnoses. Participants were asked to describe symptoms and impacts experienced in the past and currently; and then they were asked which symptoms and impacts were most bothersome or disruptive to their lives. (e.g., “ Tell me about your Parkinson’s. What kind of symptoms do (did) you experience? ”) This open-ended question established rapport with the interview participants and provided further insight into which symptoms to probe to explore the participant’s early-stage experience in greater depth. Interview questions from this discussion can be found in Appendix A . The second phase started with cognitive debriefing questions to explore participants’ understanding and relevance of the PGI-S which involved working systematically through the individual item, response options, recall period, and instructions. (e.g., “ Over the past week, how would you describe the severity of your Parkinson’s? No problem, Very mild, Mild, Moderate, Severe, Very severe ). Participants were further probed to understand their current perception of disease severity and description of symptoms and impacts experienced), then, participants were asked to describe how they envisioned their disease symptoms and impacts. would progress or may improve at each level of severity on the PGI-S scale. Interview questions from this discussion can be found in Appendix B . 2.2 Study Population and Design This observational cross-sectional study was conducted through web-based interviews with 17 early-stage participants recruited in the United States. Participants were between 41 and 80 years of age and had a clinician-confirmed diagnosis of Parkinson’s. Participant recruitment was focused on the stage of Parkinson's rather than age, and all participants in this study were classified as early-stage patients (i.e., Stage 1-2.5 on the mH&Y). Inclusion criteria required participants to be treatment-naïve or only recently started monotherapy with an anti-Parkinson’s medication within 3 years of screening. Participant medication class had to have stayed the same during the prior 3 years. Any participants with a diagnosis of secondary or atypical Parkinsonism or who had active medical or psychiatric conditions that would have compromised their ability to participate in the study were deemed ineligible to participate. Study participants were recruited through referrals from family practices and/or neurologists. 2.3 Ethics Study materials were reviewed and approved by a centralized Internal Review Board (WCG IRB Study #1334453; IRB Tracking #20222833). 2.4 Qualitative Data Analysis All interview data was audio-recorded and transcribed verbatim. The transcribed data were analyzed using NVivo v13.0, a software package that is designed to facilitate the systematic review, coding, and analysis of qualitative data. Transcript data were analyzed using thematic analysis, which is an iterative process that involves carefully reading transcripts and identifying patterns and themes, this iterative process continued until no new concepts were identified. Saturation [ 18 ] of concepts was achieved within the first 13 interviews; however, interviews were continued to obtain further valuable information, to develop a qualitative description of the study objectives: what symptoms led to diagnosis, current symptoms and impacts, and anticipated symptom severity and impacts. Analysis of the PGI-S Debriefing Data from each participant was analyzed to assess the understanding or interpretation of the item (e.g., “ What does “severity” mean to you ?”), understanding of the response options for the measure, and what each level of severity meant to participants in terms of likely symptom and impacts experienced (e.g., “ What do you think your symptoms would be like for No problems, Very Mild, Mild, Moderate, Severe, Very Severe Parkinson’s severity ?”). 3 Results The demographic variables of the interview sample are displayed in Table 1 (see ESM2). The clinical characteristics of the interview sample are in Table 2 (see ESM2). In total, 17 patients in early stages of Parkingson’s agreed to be interviewed. The mean age was 61.6 years and 64.7% were male. Racial categories were mostly White (n = 14; 82.4%), Black or African American (n = 2; 11.8%), and 1 (5.9%) selected “other.” Two (11.8%) identified as Hispanic/Latino under the ethnicity category. Additionally, most participants were classified in stage 1 (n = 7; 41.2%) at the time of the study, followed by stage 1.5 (n = 6; 35.3%), stage 2 (n = 3; 17.6%), and stage 2.5 (n = 1; 5.9%). 3.1 Participant Initial and Current Reported Signs/Symptoms When discussing the initial signs and symptoms participants experienced before their diagnosis, many (n = 13; 76%) noted that they had lived with symptoms without knowing or considering them as Parkinson’s symptoms, which delayed their diagnosis and treatment. While the majority of participants (n = 10; 59%) reported experiencing tremors, twitching, or muscle tics as the initial symptom which led to an official diagnosis, other first symptoms mentioned included: slowed movement and dragging feet (bradykinesia; n = 5; 29%), falling, balance issues and change in posture (postural instability; n = 5; 29%), muscle issues, pain, and stiffness (rigidity; n = 5; 29%). Current symptoms reported by participants included both motor symptoms (e.g., tremors, bradykinesia, postural instability) and non-motor symptoms. Motor symptoms were reported by all participants and included tremors (n = 16; 94%), rigidity (n = 15; 88%), postural instability (n = 13; 76%), and bradykinesia (n = 11; 65%). Every participant reported experiencing non-motor symptoms directly related to their Parkinson’s. The most frequently reported non-motor symptoms were urinary problems (e.g., leakage, urgency, and frequency n = 11; 65%), issues with loss of smell and/or taste (n = 9; 53%) and gastrointestinal issues including diarrhea, bloating, cramping and constipation (n = 8; 47%) and 3 participants expressed experiencing severe constipation. Table 3 and Table 4 provide a compilation of participant quotes about current motor and non-motor symptoms. 3.2 Most Bothersome Reported Symptoms The most bothersome symptom reported by participants (n = 16; 94%) was experiencing tremors (n = 11; 69%). More than half of these participants (n = 7; 64%) shared frustration due to the loss of control in their life due to tremors. For example, participants stated: “ I can’t control what I’m doing ” (01–003); “ there’s nothing I can do to make it stop ” (01–001); “ it’s beyond my control” (40 − 002). A few reported how visible their tremors were to others which resulted in embarrassment or shame (n = 3; 27%) and 1 shared that shaking from tremors caused trouble sleeping. Other “most” bothersome symptoms were reported by only 2–3 participants, including muscle pain (rigidity) (n = 3; 18%) and sleep disruptions (n = 2; 12%) which were explained as exacerbating all other symptoms. Lastly, 1 participant reported postural instability and 1 participant reported both urinary issues and constipation as their most bothersome symptoms. (See Fig. 1) 3.3 Current HRQoL Impacts Responses about how Parkinson's symptoms affected participants' lives were personal and unique to everyone, aligning with 1 participant’s definition of Parkinson’s: It means a condition that…is unique to each individual… other people I know with Parkinson’s... all have…different experiences… it’s not this perfect diagnosis…. It happens differently for every person. (03–009) Yet, despite differences in early stage experience, study results related to HRQoL impacts could be broken into 5 domains: emotional, physical, social, cognitive, and activities of daily living impacts. (See Fig. 2) Emotional Burden of Parkinson’s Nearly every participant (n = 16; 94%) spoke about the emotional burden their diagnosis had on their lives. Receiving a Parkinson’s diagnosis and contemplating the future of their disease had a significant impact, which 63% (n = 10) of 16 participants said caused anxiety and/or depression. Seven participants (n = 7; 44%) described feeling overwhelmed by the idea of how their lives would progress, and anger and frustration due to disease progression. When reflecting on the emotional burden the disease took on their lives, 7 (44%) shared the shame and embarrassment they felt due to the visible nature of Parkinson's, as the public gaze of one’s tremors and involuntary movements caused embarrassment. One participant shared their story of accusations of public drunkenness: “Why do you come out in public when you’re drinking?” And I’m like, “I don’t drink.” And she said, “Uh, lady, you’re staggering all over.” I said, “Lady, I have Parkinson’s disease (01–001) Others (n = 5; 31%) shared the burden on their mood, which impacted their family and loved ones. Parkinson's caused these participants to reflect on their mood as “crabby,” “unhappy,” “apathetic,” and “irritable.” Physical Impacts of Parkinson’s Of the 17 study participants, 15 (88%) spoke of the physical impact Parkinson’s had on them. Twelve (80%) of these participants shared that they were unable to exercise like they used to, and 7 of the 12 (58%) noted they could no longer participate in sports, like basketball or bowling. Being able to walk and remain coordinated were reported to be more difficult by 3 (20%), and difficulties writing, using a computer mouse, and swallowing pills were mentioned by 2 participants each (13%). One participant shared that they physically were no longer able to run and play with their children or grandchildren due to their Parkinson’s. Social Impacts of Parkinson’s Several participants (n = 13; 76%) reported that their Parkinson’s impacted their social activities with family and friends. Participants remarked on being more isolated and less likely to go out and be social (n = 5; 38%), being worried about the burden their Parkinson’s had on their loved ones, and reassuring their children and grandchildren that they were okay (n = 6; 46%). Two participants (15%) spontaneously remarked on the negative impacts Parkinson’s had on their intimacy (40 − 002), sex life (01–001), and body odor. Interestingly, 4 participants (31%) remarked how meaningful support groups were and how the Parkinson’s community had provided important connections and shared experiences they otherwise would not have had. One participant shared the improvement in their lives because of their connection with other patients: The Parkinson’s group that I joined... [w]e’re pretty active and I’ve met a whole lot of Parkis as we call ourselves, people with Parkinson’s disease…so we don’t have time to think about ourselves. I guess that’s the way to put it. (03–004) Cognitive Impacts of Parkinson’s Eight of the 17 participants (47%) reported experiences with mild cognitive symptom difficulties. Six of these participants (75%) spoke of memory loss, with examples given of forgetting words (n = 2/6; 33%) and forgetting people’s names (n = 1/6; 17%). Two of these 6 participants (33%) reported a direct impact of memory loss on their work lives. For example, 1 participant explained, “ I’ve been leading presentations on a call and in mid-sentence I kind of forget where I was, so I have to go look at my notes more than I usually do ” (03 − 001). Others (n = 4; 50%) reflected on cognitive decline as a feeling of “fogginess” or having “brain fog” and feeling “easily distracted” and unable to focus. Impacts of Activities of Daily Living Even at early-stages - diagnosed within 3years – Parkinson’s had a significant impact on participants’ daily lives (n = 15; 88%). Six (40%) shared frustrations with their inability to write and take notes, type on a computer, or do a crossword puzzle. Doing things around the house like home repairs and daily chores were mentioned by 6 participants (40%). Acts of self-care, such as taking a shower or bath, eating with a fork, or brushing teeth, were impactful for 6 (40%) of the 15 participants. Four (27%) mentioned changes in their voice and speech made communication difficult. Other “simple” daily activities like holding a cell phone, tying shoes, and holding a book were other impactful changes mentioned (n = 3; 20%). Some exemplary quotes of patient-reported impacts are presented in Table 5. Fourteen out of 17 (82%) were asked about which of the HRQoL impacts they found to be most bothersome. Participants most frequently reported (n = 8; 57%) that daily impacts were most disruptive. This was followed by physical impacts (n = 7; 50%) and emotional impacts (n = 6; 43%). Others expressed the most bothersome impacts to be those related to their social life (n = 2; 14%) and the impact to their sleep (n = 1; 7%). 3.4 Understanding Perceived Severity in Early-stages Parkinson’s During the cognitive debriefing phase of the interview, participants were asked to read the PGI-S items out loud and to provide their thought process as they selected the response option that applied to them in the past 7 days. Table 6 provides a compilation of the responses given by participants. The majority stated their early stage symptoms were either currently at a mild (n = 8; 47%) or a moderate severity level (n = 6; 35%). 3.5 Current Perceived Severity (via PGI-S Placement) As part of the study objective to assess participants’ descriptions of severity using the PGI-S, participants engaged in a cognitive debriefing exercise to better understand their current perception of severity. Participants were asked to select the response option that best applied to them in the past 7 days followed by how they interpreted the severity level of the remaining response options. There were no participants who opted for the “no problems” response. However, when probed to think about how their current symptoms would feel at a “no problems” level, most (n = 8; 47%) reported they would expect “no symptoms at all” and 3 participants (18%), reflecting on symptoms in a “no problems” state, shared they would expect to have “no tremors” when thinking of this response. Additionally, participants expressed being able to do everything they used to do, such as hobbies they enjoyed and having more energy to complete daily tasks. Describing this feeling, participant (03–004) shared, “[ I would be ] full of energy…on point with daily tasks…. Upbeat, social… describes it. ” Two participants (12%) selected “very mild” on the scale as their current state of symptom severity. The descriptions these 2 participants gave of “very mild” were in alignment with the remaining sample (n = 15; 88%) descriptions. When asked how they defined “very mild” symptom severity, 10 (59%) interpreted this to be less bothersome or a reduction in symptom severity. For participants whose current severity state was more severe than “very mild” (i.e., mild to very severe) 5 participants (31%) described this “very mild” state of severity in terms of their tremor experiences. These participants shared that “very mild” meant their tremors were “ barely noticeable ” (01–005) or they were “ not be very aware of them. ” (01–004) Several of the participants (n = 9, 53%) also reflected on the severity responses in terms of their HRQoL impacts and expressed that “very mild” would mean better sleep, increased energy, more engagement in social settings, and generally less emotional. For example, 1 participant shared how being in a state of “very mild” severity would mean: “ I could jump in the shower, change clothes, grab my purse, go shopping… and visit with my friends.” (0–001) Some participants (n = 8; 47%) selected “mild” for their current symptom severity on the scale. These participants described “mild” in terms of the frequency with which they experienced their tremors (n = 5/8; 63%), rigidity (stiffness and muscle pain n = 5, 63%), and non-motor symptoms including, constipation and urinary problem (n = 1/8; 13%). For example, these participants expressed “mild” as having “a little more,” “few,” and “some” symptoms. They also described how “mild” severity symptoms affected their day-to-day lives with half (n = 4/8; 50%) reporting a “mild” state would result in no impacts to their lives. One participant (03 − 002) describes, “[t] hat’s why it’s mild…… it doesn’t impact my lifestyle.” Other symptoms mentioned by 1 participant included mild sleep disruptions, emotional, social, work, and physical impacts. Lastly, 6 participants who selected “moderate” (35%) and 1 participant who selected “severe” (6%) for their current state of symptom severity, were the most severe response options selected by early-stage participants at the time of the interview. The 6 participants who selected “moderate” reported an increase in frequency and severity of tremors. Other symptoms reported by these 6 participants included rigidity (stiffness, n = 2/6; 33%), and bradykinesia (affected movement, n = 1/6; 17%). The increase in frequency and severity of tremors affected all participants who selected a “moderate” severity level, explained by 1 participant, “ Moderate would be some effects on functionality… there are some definite experiences that I have that affect my day-to-day life over a week…. That can get in the way of me feeling like at full function” (03–009). Aside from an increase in the severity of their tremors, participants spoke of the impacts the increased severity had on their ability to live their daily lives. An increase in the severity of their tremors resulted in their inability to shop, an increase in instability in the hands caused them to drop items, and not being able to plan events or complete to-do lists or simple chores like taking out the garbage. Two of the 6 participants (33%) experienced sleep loss, fatigue, and impacts on their social lives as well. Others (reported by 1 each) described memory issues and feelings of apathy. To note, the 1 participant who selected “severe” severity seemed to struggle with responding and comprehending the cognitive debriefing exercise, therefore only responses from the “moderate” severity group are presented. 3.6 Future Anticipated Severity After sharing their assessment of current severity and conceptualizing their current state of severity using the different PGI-S response options, participants were asked to describe how they may anticipate severity, starting with the scale placement they had not experienced. For example, a participant who was in a current state of “moderate” severity placement, would hypothesize how a state of “severe” may feel followed by how a state of “very severe” severity may feel, and so forth. Starting at mild severity on the scale, 2 (12%) participants who rated their current experience at a “very mild” severity state were asked to describe symptoms and impacts for a “mild” severity. Both participants found that there was a minor difference between a very mild and mild severity as described by the following participant: “. I think very mild [is] too similar to see a difference… if I was being impacted moderately then…, that would have more severity and more impact ” (01–004). The 2 participants spoke about tremors as mild and not impactful. One participant spoke about rigidity to leg cramps as mild and causing some sleep impacts. The other participant stated that a good night’s sleep would reduce the impact on their mild symptoms. Participants who chose “very mild” and “mild” (n = 10; 59%) as their current experience were asked to describe “moderate” severity in terms of symptoms and impacts. Six (60%) of the 10 participants described “moderate” severity as an increase in symptoms and having more “visible” symptoms such as changes in writing, facial expression, and voice. The significant impacts of a moderate level of severity on the PGI- S was summarized by 1 participant to be quite “impactful” explaining, “ [w]hen you start getting to moderate symptoms, that could be very impactful, and that concerns me ” (03–008). Half (n = 5; 50%) of the participants reported that they would need assistance with doing daily tasks like driving and feeding themselves. Sixteen (94%) participants selected a response option between “very mild” and “moderate.” All participants were asked to describe what they imagined symptoms and impacts would be like at a severe level. Responses to how symptoms would be experienced at a “severe” state were varied. Ten of the 16 participants (63%) spoke of a loss of mobility and 4 (25%) spoke of needing a walker or wheelchair. Six (38%) participants conceptualized “severe” to mean needing a full-time caregiver to assist with their needs. For example, 1 participant summarizes what they believe a “severe” state of symptoms could be as follows: I think the shaking will be worse. I think walking will be impaired. I think the memory will be slower. Balance would be affected…It would completely change my life because it would be less mobility (01–005) Finally, all participants (n = 17) were asked to describe what they expected the severity of symptoms would be and how those symptoms would impact their day-to-day life for “very severe.” Participants’ descriptions continued to increase in severity around being in a state of immobility and in need of a wheelchair due to their inability to walk on their own (n = 11; 65%). Eight participants (47%) also mentioned the need for a constant caregiver or the need to be admitted to a full-time healthcare facility (n = 3;18%) at this level of severity. One participant summed up their hypothetical summary of “very severe” as follows: I will probably have to live with somebody…somebody feeding me and helping bathe me and all the other… I could be close to bedridden… if it’s very severe and working would be non-existent. (01–003) Table 7 provides a summary of PGI-S (ESM 2). 4 Discussion In this study, we sought to understand the symptoms and impacts experienced by an early-stage Parkinson’s population. Additionally, we investigated perceived thoughts on progression of disease at different severity levels with the PGI-S providing a well-defined framework for the concept of severity. There have been many notable advances in detection and assessment of Parkinson’s over the last several years [ 19 ], despite these advancements researchers must be mindful that disease severity and impacts are highly personal and most accurately assessed through the evaluation of personal experience. Obtaining the personal disease journey of these 17 participants at the early stages of Parkinson’s furnished insight into how early-stage Parkinson's is experienced, which is a sub-group of patients few other studies have investigated. Participants shared their symptom severity experiences, and how living in the early stages impacts their lives. As part of the eligibility requirements to participate in this study, we designed the recruitment to be limited to participants who had lower scores on the mH&Y scale. While mH&Y scoring requirements of 1.0–2.5 provided more limitations in our recruitment strategy, it ensured that the data on severity was captured in a population who were early in their disease experience. Interestingly, when these early-stage participants were asked to rate their severity over the past 7 days using the scale, 35% stated their symptoms to be at a “moderate” level. Similar to the current literature [ 10 ], which confirms tremors as the most bothersome symptom, nearly every participant (n = 16; 94%) in this study reported tremors as the key symptom in their early stages. For individuals living with early onset PD symptoms, there was associated shame and embarrassment that was frequently so strong it caused individuals to isolate and withdraw from social and family events, highlighting that severity is not always dependent upon a disease’s advancement and the severity of a symptom can also be evaluated as severe because of the personal, lived experience. The qualitative interviews conducted in our study also demonstrate concerns about symptom discrimination in the workplace, changes in interpersonal relationships, and misperceptions of being drunk because of the shaking and tremors that Parkinson’s causes. These impacts were shared as significant to the early stages of the disease. Several participants mentioned feelings of depression, which has been identified previously as having the biggest impact on patients’ lives [ 20 – 22 ]. The stories shared in our study provide further insight into how the struggles with this disease may exacerbate symptoms of depression and more awareness of this even at an early-onset stage may help with the management of these patients. The cognitive debriefing exercise conducted using the PGI-S response options demonstrates the comprehensiveness of the measure in an early-stage population. None of the participants had issues with comprehending the items or response options in the measure and they could easily reflect on their current and hypothesized future states of symptom severity. While the PGI-S is a global measure generally used to rate the severity of a specific condition rather than a phase of a disease like the early stages of Parkinson’s, these findings show that the measure may be useful for future research wanting to look at changes in the severity. 4.1 Limitations Although 17 participants are generally considered a small sample size limitation, it is within the acceptable range of recruitment for similar qualitative studies [ 23 ]. Concept validity was considered achieved with as no new concepts were emerging in the dataset after 13 interviews. Evidence suggests that with a qualitative sample size of n = 15, researchers should reasonably expect to elicit more than 90% of concepts being elicited through n = 20 interviews [ 22 ]. While every effort was made to recruit a minimum of N = 20, our study’s eligibility criteria presented some challenges with recruiting participants who were treatment naïve or had started monotherapy with an anti-Parkinson medication within 3 years of screening for this study. Furthermore, sample sizes for cognitive debriefing studies vary upon the complexity of the measure and diversity of the patient population. Some studies have even suggested samples as small as 7 to 10 are sufficient [ 25 ]. Because the PGI-S is a global measure and the question is relatively simple, a sample of 17 participants is considered reasonable to gather information about the relevance of the severity categories and information about severity progression along the severity continuum of the measure within this population. Additional limitations included a wider range of modified Hoehn and Yahr stages (1-2.5) as this study had initially sought to mirror a clinical trial closed, and the data was repurposed for this manuscript. There are significant symptom changes that can appear from stage 1 to stage 2 that impact quality of life. At stage 1-1.5 (n = 13; 76%) a person generally has mild unilateral symptoms that typically don’t interfere with daily activity. As the disease progresses to stage 2-2.5 (n = 4; 24%) symptoms begin to that was get worse and appear bilaterally which makes daily tasks more difficult and may require the person to seek assistance from a caregiver. However, the early stages of Parkinson’s experience can vary widely due to the heterogeneous presentation of the disease [ 26 ]. Although this research was limited by an older population of participants with co-occurring chronic conditions (the mean age of participants was 61.6, receiving anti-Parkinson medication [n = 13; 76%]), the study sample age range and mean age was similar to recently published research [ 27 ]. Yet, due to the limited literature in younger populations, more research should be conducted within a younger, treatment naïve, early-stage population with fewer comorbidities. And, finally, while every effort was made to obtain a more diverse dataset, participants were disproportionately non-Hispanic, white males with a high-school education or higher. The heterogeneity of this dataset is in alignment with the demographics of an early diagnosed population in the US [ 28 ], and a recent publication that included an early-stage population [ 27 ]. A more diverse sample is recommended in future research to address the current racial disparities existing among movement disorder diagnoses [ 29 ]. 5 Conclusion While many studies have sought to understand the vast and varied impact of Parkinson’s, the population at the early stage experience of disease severity has been understudied. This study highlights that even at the early stages of the disease, individuals living with Parkinson’s experience a wide range of symptoms and associated impacts which shape their day-to-day experience and contribute to their perception of their severity. Declarations Funding: No funding was received for conducting this study. COI Statement: Authors AS, CDR, CUF and TS are employed by Clinical Outcomes Solutions. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Availability of data and materials: The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Clinical Outcome Solutions. Ethics: The study protocol was reviewed and approved by the Western Institutional Review Board-Copernicus Group (WCG IRB Study #1334453; IRB Tracking #20222833), and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Consent to Participate and Consent to Publish : Informed consent was obtained from all individual participants included in the study. The authors affirm that human research participants provided informed consent for publication of collected data for this study. Author Contributions: AW, CD, and TS conceptualized and designed this study, and approved the final protocol. AS, CUF, and CDR conducted the interviews and analyzed the data. All authors interpreted the data and read and approved the final manuscript. Acknowledgements: Medical writing and editorial assistance, under the authors’ guidance and funded by Kyowa Kirin, was provided by Emily Calderbank, MA (Clinical Outcomes Solutions, Chicago, USA) and David Navarro, BS (Clinical Outcomes Solutions, Tucson, AZ, USA). References Bloem BR, Okun MS, Klein C. Parkinson's disease. The Lancet. 2021;397(10291):2284–2303. World Health Organization. Fact Sheets: Parkinson Disease. Updated 13 June 2022. https://www.who.int/news-room/fact-sheets/detail/parkinson-disease . Von Campenhausen S, Bornschein B, Wick R, et al. Prevalence and incidence of Parkinson's disease in Europe. European neuropsychopharmacology. 2005;15(4):473–490. Marras C, Beck J, Bower J, et al. Prevalence of Parkinson’s disease across North America. NPJ Parkinson's disease. 2018;4(1):21. Goetz CG, Poewe W, Rascol O, et al. Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations the Movement Disorder Society Task Force on rating scales for Parkinson's disease. Movement disorders. 2004;19(9):1020–1028. Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology. 1967;17(5):427–427. Modestino EJ, Reinhofer A, Blum K, Amenechi C, O’Toole P. Hoehn and Yahr staging of Parkinson’s disease in relation to neuropsychological measures. Frontiers in Bioscience-Landmark. 2018;23(7):1370–1379. Hawkes CH, Del Tredici K, Braak H. A timeline for Parkinson's disease. Parkinsonism & related disorders. 2010;16(2):79–84. Templeton JM, Poellabauer C, Schneider S. Classification of Parkinson’s disease and its stages using machine learning. Scientific Reports. 2022;12(1):14036. Heusinkveld LE, Hacker ML, Turchan M, Davis TL, Charles D. Impact of tremor on patients with early stage Parkinson's disease. Frontiers in neurology. 2018;9:628. Nijhof G. Parkinson's disease as a problem of shame in public appearance. Sociology of Health & Illness. 1995;17(2):193–205. Grover S, Somaiya M, Kumar S, Avasthi A. Psychiatric aspects of Parkinson’s disease. Journal of neurosciences in rural practice. 2015;6(01):065–076. Menon B, Nayar R, Kumar S, et al. Parkinson's disease, depression, and quality-of-life. Indian journal of psychological medicine. 2015;37(2):144–148. Byrom B, Breedon P, Tulkki-Wilke R, Platko J. Meaningful change: Defining the interpretability of changes in endpoints derived from interactive and mHealth technologies in healthcare and clinical research. Journal of Rehabilitation and Assistive Technologies Engineering. 2020;7doi: 10.1177/2055668319892778 Martínez-Martín P, Rojo-Abuin JM, Rodríguez-Violante M, et al. Analysis of four scales for global severity evaluation in Parkinson’s disease. npj Parkinson's Disease. 2016;2(1):1–6. Martinez-Martin P, Wetmore JB, Arbelo JM, Catalán MJ, Valldeoriola F, Rodriguez-Blazquez C. Validation study of the Parkinson’s Fatigue Scale in advanced Parkinson’s disease. Patient Related Outcome Measures. 2019:141–152. Löhle M, Bremer A, Gandor F, et al. Validation of the PD home diary for assessment of motor fluctuations in advanced Parkinson’s disease. npj Parkinson's Disease. 2022;8(1):69. Francis JJ, Johnston M, Robertson C, et al. What is an adequate sample size? Operationalising data saturation for theory-based interview studies. Psychology and health. 2010;25(10):1229–1245. Yang Y, Yuan Y, Zhang G, et al. Artificial intelligence-enabled detection and assessment of Parkinson’s disease using nocturnal breathing signals. Nature medicine. 2022;28(10):2207–2215. Ahn S, Springer K, Gibson JS. Social withdrawal in Parkinson's disease: A scoping review. Geriatric Nursing. 2022;48:251–261. McKinlay A, Grace R, Dalrymple-Alford J, Anderson T, Fink J, Roger D. A profile of neuropsychiatric problems and their relationship to quality of life for Parkinson's disease patients without dementia. Parkinsonism & related disorders. 2008;14(1):37–42. Soh S-E, Morris ME, McGinley JL. Determinants of health-related quality of life in Parkinson’s disease: a systematic review. Parkinsonism & related disorders. 2011;17(1):1–9. Hennink MM, Kaiser BN, Marconi VC. Code saturation versus meaning saturation: how many interviews are enough? Qualitative health research. 2017;27(4):591–608. Rothman M, Burke L, Erickson P, Leidy NK, Patrick DL, Petrie CD. Use of existing patient-reported outcome (PRO) instruments and their modification: the ISPOR Good Research Practices for Evaluating and Documenting Content Validity for the Use of Existing Instruments and Their Modification PRO Task Force Report. Value in Health. 2009;12(8):1075–1083. Willis GB. Cognitive interviewing: A tool for improving questionnaire design . sage publications; 2004. Parkinson's Foundation. Stages of Parkinson's. https://www.parkinson.org/understanding-parkinsons/what-is-parkinsons/stages . Deal LS, Andrae DA, Myers DE, Johnson N, Foster B, Evans CJ. The Measurement Performance of the Parkinson's Disease Activities of Daily Living, Interference, and Dependence Instrument. Frontiers in Neurology. 2022;13:760174. Dahodwala N, Siderowf A, Xie M, Noll E, Stern M, Mandell DS. Racial differences in the diagnosis of Parkinson's disease. Movement Disorders. 2009;24(8):1200–1205. Nwabuobi L, Agee J, Gilbert R. Racial and social disparities in health and health care delivery among patients with parkinson’s disease and related disorders in a multiracial clinical setting. Journal of Cross-Cultural Gerontology. 2021;36(3):253–263. Tables Table 1 to 7 are available in the Supplementary Files section. 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-4731346","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":338561776,"identity":"fae41809-28b0-47e5-982f-812869ef70d1","order_by":0,"name":"A Williams","email":"","orcid":"","institution":"Kyowa Kirin International, Health Economic and Outcomes Research","correspondingAuthor":false,"prefix":"","firstName":"A","middleName":"","lastName":"Williams","suffix":""},{"id":338561777,"identity":"af4d160c-0f5e-4e41-bf51-ca404badceb1","order_by":1,"name":"Angela Stroupe","email":"data:image/png;base64,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","orcid":"","institution":"Clinical Outcome Assessments","correspondingAuthor":true,"prefix":"","firstName":"Angela","middleName":"","lastName":"Stroupe","suffix":""},{"id":338561778,"identity":"f1badd74-f72e-4267-b254-dd29fe2ce6ee","order_by":2,"name":"C del Rosario","email":"","orcid":"","institution":"Clinical Outcome 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Research","correspondingAuthor":false,"prefix":"","firstName":"C","middleName":"","lastName":"Durlach","suffix":""}],"badges":[],"createdAt":"2024-07-12 15:38:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4731346/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4731346/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63419062,"identity":"55133bc2-0b49-475a-90e4-d83ef5386da9","added_by":"auto","created_at":"2024-08-28 02:26:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":160782,"visible":true,"origin":"","legend":"\u003cp\u003eParticipant Symptom Experience\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4731346/v1/23e2a7b05020f08d1ede51e3.png"},{"id":63419060,"identity":"17386b71-28d3-4b91-84b3-d512637c0e84","added_by":"auto","created_at":"2024-08-28 02:26:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":208071,"visible":true,"origin":"","legend":"\u003cp\u003eHealth-related Quality of Life (HRQoL) Impacts\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4731346/v1/20cf9c664d075c92e6d3b45b.png"},{"id":66284431,"identity":"699a1319-8634-4b4f-9a32-aaebd9e86810","added_by":"auto","created_at":"2024-10-09 16:32:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":867691,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4731346/v1/13c781f7-860c-499b-9dc1-d0bd76fbe042.pdf"},{"id":63419964,"identity":"c5805120-b72b-4eac-a8cd-1867965f5fa6","added_by":"auto","created_at":"2024-08-28 02:34:16","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":177730,"visible":true,"origin":"","legend":"","description":"","filename":"KK1021SupplementaryMaterialDiscoverMedicine.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4731346/v1/04e4ae906be875d350379259.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Qualitative Study Exploring Patient Global Impression of Disease Severity in Early Stages of Parkinson’s Disease.","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eParkinson\u0026rsquo;s Disease (Parkinson\u0026rsquo;s) is a neurodegenerative disorder caused by the loss of dopamine producing brain cells used to control the body\u0026rsquo;s movements. Affecting approximately 8.5\u0026nbsp;million people globally [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], Parkinson\u0026rsquo;s is the second most common neurological disorder.\u003c/p\u003e \u003cp\u003eEarly to late-stage Parkinson's is profiled as transitioning from stages 1 and 2 to stages 3\u0026ndash;5 on the modified Hoehn and Yahr scale (mH\u0026amp;Y) [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Symptoms continue to worsen over a span of 20 years [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In Stage 1, mild symptoms often go unnoticed. In Stage 2, symptoms become increasingly noticeable on both sides of the body, and speech impacts begin to occur. Stage 3 is marked by imbalance and an increase in falls, and daily activities become more difficult. At Stage 4, patients often need a walking aid and assistance with tasks and are considered no longer fully independent. In Stage 5, patients are no longer mobile and often experience freezing and stumbling when they try to stand or move independently [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough the impacts of Parkinson's are the subject of a large body of research, much less focus has been placed on how early-stage patients view their current disease and its severity, how they envision disease severity will progress and what impacts their disease progression will bring. Thus, the disease experience of patients at early stages of Parkinsons remains largely under-studied. Understanding the patient perception of severity may help manage common related impacts like anxiety and depression, as it has been shown that there is low agreement between clinician-reported severity on the mH\u0026amp;Y, the Clinical Global Impression of Severity scale (CGIS), and the Clinical Impression of Severity Index (CISI) measures in comparison to the Patient Global Impression of Severity (PGI-S)[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], a commonly used measure to assess severity in progressive diseases[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. L\u0026ouml;hle et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] found that the PGI-S scale found agreement in scores only 35.1% of the time; confirming the importance of understanding disease severity from the patient's perspective.\u003c/p\u003e \u003cp\u003eThis study conducted qualitative interviews with patients at early stages of Parkinson's to ascertain how the spectrum of severity is described and perceived by this population using a patient-reported global measure of severity and to better understand the early-stage patients\u0026rsquo; experiences by exploring what symptoms and Health Related Quality of Life (HRQoL) impacts were pivotal to them.\u003c/p\u003e"},{"header":"2 Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Interview Methodology\u003c/h2\u003e \u003cp\u003eThe interview data was collected by experienced interviewers trained in capturing disease severity in early staged populations and who are experts at cognitively debriefing patient reported measures. The interviews lasted approximately 50 minutes and involved 2 phases. The first phase was a brief semi-structured discussion around the symptoms that led to participants\u0026rsquo; diagnoses. Participants were asked to describe symptoms and impacts experienced in the past and currently; and then they were asked which symptoms and impacts were most bothersome or disruptive to their lives. (e.g., \u0026ldquo;\u003cem\u003eTell me about your Parkinson\u0026rsquo;s. What kind of symptoms do (did) you experience?\u003c/em\u003e\u0026rdquo;) This open-ended question established rapport with the interview participants and provided further insight into which symptoms to probe to explore the participant\u0026rsquo;s early-stage experience in greater depth. Interview questions from this discussion can be found in \u003cb\u003eAppendix A\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e The second phase started with cognitive debriefing questions to explore participants\u0026rsquo; understanding and relevance of the PGI-S which involved working systematically through the individual item, response options, recall period, and instructions. (e.g., \u0026ldquo;\u003cem\u003eOver the past week, how would you describe the severity of your Parkinson\u0026rsquo;s? No problem, Very mild, Mild, Moderate, Severe, Very severe\u003c/em\u003e). Participants were further probed to understand their current perception of disease severity and description of symptoms and impacts experienced), then, participants were asked to describe how they envisioned their disease symptoms and impacts. would progress or may improve at each level of severity on the PGI-S scale. Interview questions from this discussion can be found in \u003cb\u003eAppendix B\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Study Population and Design\u003c/h2\u003e \u003cp\u003eThis observational cross-sectional study was conducted through web-based interviews with 17 early-stage participants recruited in the United States. Participants were between 41 and 80 years of age and had a clinician-confirmed diagnosis of Parkinson\u0026rsquo;s. Participant recruitment was focused on the stage of Parkinson's rather than age, and all participants in this study were classified as early-stage patients (i.e., Stage 1-2.5 on the mH\u0026amp;Y). Inclusion criteria required participants to be treatment-na\u0026iuml;ve or only recently started monotherapy with an anti-Parkinson\u0026rsquo;s medication within 3 years of screening. Participant medication class had to have stayed the same during the prior 3 years. Any participants with a diagnosis of secondary or atypical Parkinsonism or who had active medical or psychiatric conditions that would have compromised their ability to participate in the study were deemed ineligible to participate.\u003c/p\u003e \u003cp\u003eStudy participants were recruited through referrals from family practices and/or neurologists.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Ethics\u003c/h2\u003e \u003cp\u003eStudy materials were reviewed and approved by a centralized Internal Review Board (WCG IRB Study #1334453; IRB Tracking #20222833).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Qualitative Data Analysis\u003c/h2\u003e \u003cp\u003eAll interview data was audio-recorded and transcribed verbatim. The transcribed data were analyzed using NVivo v13.0, a software package that is designed to facilitate the systematic review, coding, and analysis of qualitative data. Transcript data were analyzed using thematic analysis, which is an iterative process that involves carefully reading transcripts and identifying patterns and themes, this iterative process continued until no new concepts were identified. Saturation [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] of concepts was achieved within the first 13 interviews; however, interviews were continued to obtain further valuable information, to develop a qualitative description of the study objectives: what symptoms led to diagnosis, current symptoms and impacts, and anticipated symptom severity and impacts.\u003c/p\u003e \u003cp\u003eAnalysis of the PGI-S Debriefing\u003c/p\u003e \u003cp\u003eData from each participant was analyzed to assess the understanding or interpretation of the item (e.g., \u0026ldquo;\u003cem\u003eWhat does \u0026ldquo;severity\u0026rdquo; mean to you\u003c/em\u003e?\u0026rdquo;), understanding of the response options for the measure, and what each level of severity meant to participants in terms of likely symptom and impacts experienced (e.g., \u0026ldquo;\u003cem\u003eWhat do you think your symptoms would be like for No problems, Very Mild, Mild, Moderate, Severe, Very Severe Parkinson\u0026rsquo;s severity\u003c/em\u003e?\u0026rdquo;).\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cp\u003eThe demographic variables of the interview sample are displayed in \u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e (see ESM2). The clinical characteristics of the interview sample are in \u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e (see ESM2). In total, 17 patients in early stages of Parkingson\u0026rsquo;s agreed to be interviewed. The mean age was 61.6 years and 64.7% were male. Racial categories were mostly White (n\u0026thinsp;=\u0026thinsp;14; 82.4%), Black or African American (n\u0026thinsp;=\u0026thinsp;2; 11.8%), and 1 (5.9%) selected \u0026ldquo;other.\u0026rdquo; Two (11.8%) identified as Hispanic/Latino under the ethnicity category. Additionally, most participants were classified in stage 1 (n\u0026thinsp;=\u0026thinsp;7; 41.2%) at the time of the study, followed by stage 1.5 (n\u0026thinsp;=\u0026thinsp;6; 35.3%), stage 2 (n\u0026thinsp;=\u0026thinsp;3; 17.6%), and stage 2.5 (n\u0026thinsp;=\u0026thinsp;1; 5.9%).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Participant Initial and Current Reported Signs/Symptoms\u003c/h2\u003e \u003cp\u003eWhen discussing the initial signs and symptoms participants experienced before their diagnosis, many (n\u0026thinsp;=\u0026thinsp;13; 76%) noted that they had lived with symptoms without knowing or considering them as Parkinson\u0026rsquo;s symptoms, which delayed their diagnosis and treatment. While the majority of participants (n\u0026thinsp;=\u0026thinsp;10; 59%) reported experiencing tremors, twitching, or muscle tics as the initial symptom which led to an official diagnosis, other first symptoms mentioned included: slowed movement and dragging feet (bradykinesia; n\u0026thinsp;=\u0026thinsp;5; 29%), falling, balance issues and change in posture (postural instability; n\u0026thinsp;=\u0026thinsp;5; 29%), muscle issues, pain, and stiffness (rigidity; n\u0026thinsp;=\u0026thinsp;5; 29%).\u003c/p\u003e \u003cp\u003eCurrent symptoms reported by participants included both motor symptoms (e.g., tremors, bradykinesia, postural instability) and non-motor symptoms. Motor symptoms were reported by all participants and included tremors (n\u0026thinsp;=\u0026thinsp;16; 94%), rigidity (n\u0026thinsp;=\u0026thinsp;15; 88%), postural instability (n\u0026thinsp;=\u0026thinsp;13; 76%), and bradykinesia (n\u0026thinsp;=\u0026thinsp;11; 65%). Every participant reported experiencing non-motor symptoms directly related to their Parkinson\u0026rsquo;s. The most frequently reported non-motor symptoms were urinary problems (e.g., leakage, urgency, and frequency n\u0026thinsp;=\u0026thinsp;11; 65%), issues with loss of smell and/or taste (n\u0026thinsp;=\u0026thinsp;9; 53%) and gastrointestinal issues including diarrhea, bloating, cramping and constipation (n\u0026thinsp;=\u0026thinsp;8; 47%) and 3 participants expressed experiencing severe constipation. \u003cb\u003eTable\u0026nbsp;3\u003c/b\u003e and \u003cb\u003eTable\u0026nbsp;4\u003c/b\u003e provide a compilation of participant quotes about current motor and non-motor symptoms.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Most Bothersome Reported Symptoms\u003c/h2\u003e \u003cp\u003eThe most bothersome symptom reported by participants (n\u0026thinsp;=\u0026thinsp;16; 94%) was experiencing tremors (n\u0026thinsp;=\u0026thinsp;11; 69%). More than half of these participants (n\u0026thinsp;=\u0026thinsp;7; 64%) shared frustration due to the loss of control in their life due to tremors. For example, participants stated: \u0026ldquo;\u003cem\u003eI can\u0026rsquo;t control what I\u0026rsquo;m doing\u003c/em\u003e\u0026rdquo; (01\u0026ndash;003); \u0026ldquo;\u003cem\u003ethere\u0026rsquo;s nothing I can do to make it stop\u003c/em\u003e\u0026rdquo; (01\u0026ndash;001); \u0026ldquo;\u003cem\u003eit\u0026rsquo;s beyond my control\u0026rdquo;\u003c/em\u003e (40\u0026thinsp;\u0026minus;\u0026thinsp;002). A few reported how visible their tremors were to others which resulted in embarrassment or shame (n\u0026thinsp;=\u0026thinsp;3; 27%) and 1 shared that shaking from tremors caused trouble sleeping.\u003c/p\u003e \u003cp\u003eOther \u0026ldquo;most\u0026rdquo; bothersome symptoms were reported by only 2\u0026ndash;3 participants, including muscle pain (rigidity) (n\u0026thinsp;=\u0026thinsp;3; 18%) and sleep disruptions (n\u0026thinsp;=\u0026thinsp;2; 12%) which were explained as exacerbating all other symptoms. Lastly, 1 participant reported postural instability and 1 participant reported both urinary issues and constipation as their most bothersome symptoms. (See \u003cb\u003eFig.\u0026nbsp;1)\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Current HRQoL Impacts\u003c/h2\u003e \u003cp\u003eResponses about how Parkinson's symptoms affected participants' lives were personal and unique to everyone, aligning with 1 participant\u0026rsquo;s definition of Parkinson\u0026rsquo;s:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u003cem\u003eIt means a condition that\u0026hellip;is unique to each individual\u0026hellip; other people I know with Parkinson\u0026rsquo;s... all have\u0026hellip;different experiences\u0026hellip; it\u0026rsquo;s not this perfect diagnosis\u0026hellip;. It happens differently for every person. (03\u0026ndash;009)\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eYet, despite differences in early stage experience, study results related to HRQoL impacts could be broken into 5 domains: emotional, physical, social, cognitive, and activities of daily living impacts. (See \u003cb\u003eFig.\u0026nbsp;2)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eEmotional Burden of Parkinson\u0026rsquo;s\u003c/p\u003e \u003cp\u003eNearly every participant (n\u0026thinsp;=\u0026thinsp;16; 94%) spoke about the emotional burden their diagnosis had on their lives. Receiving a Parkinson\u0026rsquo;s diagnosis and contemplating the future of their disease had a significant impact, which 63% (n\u0026thinsp;=\u0026thinsp;10) of 16 participants said caused anxiety and/or depression. Seven participants (n\u0026thinsp;=\u0026thinsp;7; 44%) described feeling overwhelmed by the idea of how their lives would progress, and anger and frustration due to disease progression. When reflecting on the emotional burden the disease took on their lives, 7 (44%) shared the shame and embarrassment they felt due to the visible nature of Parkinson's, as the public gaze of one\u0026rsquo;s tremors and involuntary movements caused embarrassment. One participant shared their story of accusations of public drunkenness:\u003c/p\u003e \u003cp\u003e \u003cem\u003e\u0026ldquo;Why do you come out in public when you\u0026rsquo;re drinking?\u0026rdquo; And I\u0026rsquo;m like, \u0026ldquo;I don\u0026rsquo;t drink.\u0026rdquo; And she said, \u0026ldquo;Uh, lady, you\u0026rsquo;re staggering all over.\u0026rdquo; I said, \u0026ldquo;Lady, I have Parkinson\u0026rsquo;s disease (01\u0026ndash;001)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eOthers (n\u0026thinsp;=\u0026thinsp;5; 31%) shared the burden on their mood, which impacted their family and loved ones. Parkinson's caused these participants to reflect on their mood as \u0026ldquo;crabby,\u0026rdquo; \u0026ldquo;unhappy,\u0026rdquo; \u0026ldquo;apathetic,\u0026rdquo; and \u0026ldquo;irritable.\u0026rdquo;\u003c/p\u003e \u003cp\u003ePhysical Impacts of Parkinson\u0026rsquo;s\u003c/p\u003e \u003cp\u003eOf the 17 study participants, 15 (88%) spoke of the physical impact Parkinson\u0026rsquo;s had on them. Twelve (80%) of these participants shared that they were unable to exercise like they used to, and 7 of the 12 (58%) noted they could no longer participate in sports, like basketball or bowling. Being able to walk and remain coordinated were reported to be more difficult by 3 (20%), and difficulties writing, using a computer mouse, and swallowing pills were mentioned by 2 participants each (13%). One participant shared that they physically were no longer able to run and play with their children or grandchildren due to their Parkinson\u0026rsquo;s.\u003c/p\u003e \u003cp\u003eSocial Impacts of Parkinson\u0026rsquo;s\u003c/p\u003e \u003cp\u003eSeveral participants (n\u0026thinsp;=\u0026thinsp;13; 76%) reported that their Parkinson\u0026rsquo;s impacted their social activities with family and friends. Participants remarked on being more isolated and less likely to go out and be social (n\u0026thinsp;=\u0026thinsp;5; 38%), being worried about the burden their Parkinson\u0026rsquo;s had on their loved ones, and reassuring their children and grandchildren that they were okay (n\u0026thinsp;=\u0026thinsp;6; 46%). Two participants (15%) spontaneously remarked on the negative impacts Parkinson\u0026rsquo;s had on their intimacy (40\u0026thinsp;\u0026minus;\u0026thinsp;002), sex life (01\u0026ndash;001), and body odor. Interestingly, 4 participants (31%) remarked how meaningful support groups were and how the Parkinson\u0026rsquo;s community had provided important connections and shared experiences they otherwise would not have had. One participant shared the improvement in their lives because of their connection with other patients:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u003cem\u003eThe Parkinson\u0026rsquo;s group that I joined... [w]e\u0026rsquo;re pretty active and I\u0026rsquo;ve met a whole lot of Parkis as we call ourselves, people with Parkinson\u0026rsquo;s disease\u0026hellip;so we don\u0026rsquo;t have time to think about ourselves. I guess that\u0026rsquo;s the way to put it. (03\u0026ndash;004)\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eCognitive Impacts of Parkinson\u0026rsquo;s\u003c/p\u003e \u003cp\u003eEight of the 17 participants (47%) reported experiences with mild cognitive symptom difficulties. Six of these participants (75%) spoke of memory loss, with examples given of forgetting words (n\u0026thinsp;=\u0026thinsp;2/6; 33%) and forgetting people\u0026rsquo;s names (n\u0026thinsp;=\u0026thinsp;1/6; 17%). Two of these 6 participants (33%) reported a direct impact of memory loss on their work lives. For example, 1 participant explained, \u0026ldquo;\u003cem\u003eI\u0026rsquo;ve been leading presentations on a call and in mid-sentence I kind of forget where I was, so I have to go look at my notes more than I usually do\u003c/em\u003e\u0026rdquo; (03\u0026thinsp;\u0026minus;\u0026thinsp;001). Others (n\u0026thinsp;=\u0026thinsp;4; 50%) reflected on cognitive decline as a feeling of \u0026ldquo;fogginess\u0026rdquo; or having \u0026ldquo;brain fog\u0026rdquo; and feeling \u0026ldquo;easily distracted\u0026rdquo; and unable to focus.\u003c/p\u003e \u003cp\u003eImpacts of Activities of Daily Living\u003c/p\u003e \u003cp\u003eEven at early-stages - diagnosed within 3years \u0026ndash; Parkinson\u0026rsquo;s had a significant impact on participants\u0026rsquo; daily lives (n\u0026thinsp;=\u0026thinsp;15; 88%). Six (40%) shared frustrations with their inability to write and take notes, type on a computer, or do a crossword puzzle. Doing things around the house like home repairs and daily chores were mentioned by 6 participants (40%). Acts of self-care, such as taking a shower or bath, eating with a fork, or brushing teeth, were impactful for 6 (40%) of the 15 participants. Four (27%) mentioned changes in their voice and speech made communication difficult. Other \u0026ldquo;simple\u0026rdquo; daily activities like holding a cell phone, tying shoes, and holding a book were other impactful changes mentioned (n\u0026thinsp;=\u0026thinsp;3; 20%). Some exemplary quotes of patient-reported impacts are presented in \u003cb\u003eTable\u0026nbsp;5.\u003c/b\u003e Fourteen out of 17 (82%) were asked about which of the HRQoL impacts they found to be most bothersome. Participants most frequently reported (n\u0026thinsp;=\u0026thinsp;8; 57%) that daily impacts were most disruptive. This was followed by physical impacts (n\u0026thinsp;=\u0026thinsp;7; 50%) and emotional impacts (n\u0026thinsp;=\u0026thinsp;6; 43%). Others expressed the most bothersome impacts to be those related to their social life (n\u0026thinsp;=\u0026thinsp;2; 14%) and the impact to their sleep (n\u0026thinsp;=\u0026thinsp;1; 7%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Understanding Perceived Severity in Early-stages Parkinson\u0026rsquo;s\u003c/h2\u003e \u003cp\u003e During the cognitive debriefing phase of the interview, participants were asked to read the PGI-S items out loud and to provide their thought process as they selected the response option that applied to them in the past 7 days. \u003cb\u003eTable\u0026nbsp;6\u003c/b\u003e provides a compilation of the responses given by participants. The majority stated their early stage symptoms were either currently at a mild (n\u0026thinsp;=\u0026thinsp;8; 47%) or a moderate severity level (n\u0026thinsp;=\u0026thinsp;6; 35%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Current Perceived Severity (via PGI-S Placement)\u003c/h2\u003e \u003cp\u003e As part of the study objective to assess participants\u0026rsquo; descriptions of severity using the PGI-S, participants engaged in a cognitive debriefing exercise to better understand their current perception of severity. Participants were asked to select the response option that best applied to them in the past 7 days followed by how they interpreted the severity level of the remaining response options.\u003c/p\u003e \u003cp\u003eThere were no participants who opted for the \u0026ldquo;no problems\u0026rdquo; response. However, when probed to think about how their current symptoms would feel at a \u0026ldquo;no problems\u0026rdquo; level, most (n\u0026thinsp;=\u0026thinsp;8; 47%) reported they would expect \u0026ldquo;no symptoms at all\u0026rdquo; and 3 participants (18%), reflecting on symptoms in a \u0026ldquo;no problems\u0026rdquo; state, shared they would expect to have \u0026ldquo;no tremors\u0026rdquo; when thinking of this response. Additionally, participants expressed being able to do everything they used to do, such as hobbies they enjoyed and having more energy to complete daily tasks. Describing this feeling, participant (03\u0026ndash;004) shared, \u0026ldquo;[\u003cem\u003eI would be\u003c/em\u003e] \u003cem\u003efull of energy\u0026hellip;on point with daily tasks\u0026hellip;. Upbeat, social\u0026hellip; describes it.\u003c/em\u003e\u0026rdquo;\u003c/p\u003e \u003cp\u003eTwo participants (12%) selected \u0026ldquo;very mild\u0026rdquo; on the scale as their current state of symptom severity. The descriptions these 2 participants gave of \u0026ldquo;very mild\u0026rdquo; were in alignment with the remaining sample (n\u0026thinsp;=\u0026thinsp;15; 88%) descriptions. When asked how they defined \u0026ldquo;very mild\u0026rdquo; symptom severity, 10 (59%) interpreted this to be less bothersome or a reduction in symptom severity. For participants whose current severity state was more severe than \u0026ldquo;very mild\u0026rdquo; (i.e., mild to very severe) 5 participants (31%) described this \u0026ldquo;very mild\u0026rdquo; state of severity in terms of their tremor experiences. These participants shared that \u0026ldquo;very mild\u0026rdquo; meant their tremors were \u0026ldquo;\u003cem\u003ebarely noticeable\u003c/em\u003e\u0026rdquo; (01\u0026ndash;005) or they were \u0026ldquo;\u003cem\u003enot be very aware of them.\u003c/em\u003e\u0026rdquo; (01\u0026ndash;004)\u003c/p\u003e \u003cp\u003eSeveral of the participants (n\u0026thinsp;=\u0026thinsp;9, 53%) also reflected on the severity responses in terms of their HRQoL impacts and expressed that \u0026ldquo;very mild\u0026rdquo; would mean better sleep, increased energy, more engagement in social settings, and generally less emotional. For example, 1 participant shared how being in a state of \u0026ldquo;very mild\u0026rdquo; severity would mean: \u0026ldquo;\u003cem\u003eI could jump in the shower, change clothes, grab my purse, go shopping\u0026hellip; and visit with my friends.\u0026rdquo;\u003c/em\u003e (0\u0026ndash;001)\u003c/p\u003e \u003cp\u003eSome participants (n\u0026thinsp;=\u0026thinsp;8; 47%) selected \u0026ldquo;mild\u0026rdquo; for their current symptom severity on the scale. These participants described \u0026ldquo;mild\u0026rdquo; in terms of the frequency with which they experienced their tremors (n\u0026thinsp;=\u0026thinsp;5/8; 63%), rigidity (stiffness and muscle pain n\u0026thinsp;=\u0026thinsp;5, 63%), and non-motor symptoms including, constipation and urinary problem (n\u0026thinsp;=\u0026thinsp;1/8; 13%). For example, these participants expressed \u0026ldquo;mild\u0026rdquo; as having \u0026ldquo;a little more,\u0026rdquo; \u0026ldquo;few,\u0026rdquo; and \u0026ldquo;some\u0026rdquo; symptoms. They also described how \u0026ldquo;mild\u0026rdquo; severity symptoms affected their day-to-day lives with half (n\u0026thinsp;=\u0026thinsp;4/8; 50%) reporting a \u0026ldquo;mild\u0026rdquo; state would result in no impacts to their lives. One participant (03\u0026thinsp;\u0026minus;\u0026thinsp;002) describes, \u0026ldquo;[t]\u003cem\u003ehat\u0026rsquo;s why it\u0026rsquo;s mild\u0026hellip;\u0026hellip; it doesn\u0026rsquo;t impact my lifestyle.\u0026rdquo;\u003c/em\u003e Other symptoms mentioned by 1 participant included mild sleep disruptions, emotional, social, work, and physical impacts.\u003c/p\u003e \u003cp\u003eLastly, 6 participants who selected \u0026ldquo;moderate\u0026rdquo; (35%) and 1 participant who selected \u0026ldquo;severe\u0026rdquo; (6%) for their current state of symptom severity, were the most severe response options selected by early-stage participants at the time of the interview. The 6 participants who selected \u0026ldquo;moderate\u0026rdquo; reported an increase in frequency and severity of tremors. Other symptoms reported by these 6 participants included rigidity (stiffness, n\u0026thinsp;=\u0026thinsp;2/6; 33%), and bradykinesia (affected movement, n\u0026thinsp;=\u0026thinsp;1/6; 17%). The increase in frequency and severity of tremors affected all participants who selected a \u0026ldquo;moderate\u0026rdquo; severity level, explained by 1 participant, \u0026ldquo;\u003cem\u003eModerate would be some effects on functionality\u0026hellip; there are some definite experiences that I have that affect my day-to-day life over a week\u0026hellip;. That can get in the way of me feeling like at full function\u0026rdquo;\u003c/em\u003e (03\u0026ndash;009). Aside from an increase in the severity of their tremors, participants spoke of the impacts the increased severity had on their ability to live their daily lives. An increase in the severity of their tremors resulted in their inability to shop, an increase in instability in the hands caused them to drop items, and not being able to plan events or complete to-do lists or simple chores like taking out the garbage. Two of the 6 participants (33%) experienced sleep loss, fatigue, and impacts on their social lives as well. Others (reported by 1 each) described memory issues and feelings of apathy. To note, the 1 participant who selected \u0026ldquo;severe\u0026rdquo; severity seemed to struggle with responding and comprehending the cognitive debriefing exercise, therefore only responses from the \u0026ldquo;moderate\u0026rdquo; severity group are presented.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.6 Future Anticipated Severity\u003c/h2\u003e \u003cp\u003eAfter sharing their assessment of current severity and conceptualizing their current state of severity using the different PGI-S response options, participants were asked to describe how they may anticipate severity, starting with the scale placement they had not experienced. For example, a participant who was in a current state of \u0026ldquo;moderate\u0026rdquo; severity placement, would hypothesize how a state of \u0026ldquo;severe\u0026rdquo; may feel followed by how a state of \u0026ldquo;very severe\u0026rdquo; severity may feel, and so forth.\u003c/p\u003e \u003cp\u003eStarting at mild severity on the scale, 2 (12%) participants who rated their current experience at a \u0026ldquo;very mild\u0026rdquo; severity state were asked to describe symptoms and impacts for a \u0026ldquo;mild\u0026rdquo; severity. Both participants found that there was a minor difference between a very mild and mild severity as described by the following participant: \u0026ldquo;. \u003cem\u003eI think very mild [is] too similar to see a difference\u0026hellip; if I was being impacted moderately then\u0026hellip;, that would have more severity and more impact\u003c/em\u003e\u0026rdquo; (01\u0026ndash;004). The 2 participants spoke about tremors as mild and not impactful. One participant spoke about rigidity to leg cramps as mild and causing some sleep impacts. The other participant stated that a good night\u0026rsquo;s sleep would reduce the impact on their mild symptoms.\u003c/p\u003e \u003cp\u003eParticipants who chose \u0026ldquo;very mild\u0026rdquo; and \u0026ldquo;mild\u0026rdquo; (n\u0026thinsp;=\u0026thinsp;10; 59%) as their current experience were asked to describe \u0026ldquo;moderate\u0026rdquo; severity in terms of symptoms and impacts. Six (60%) of the 10 participants described \u0026ldquo;moderate\u0026rdquo; severity as an increase in symptoms and having more \u0026ldquo;visible\u0026rdquo; symptoms such as changes in writing, facial expression, and voice. The significant impacts of a moderate level of severity on the PGI- S was summarized by 1 participant to be quite \u0026ldquo;impactful\u0026rdquo; explaining, \u0026ldquo;\u003cem\u003e[w]hen you start getting to moderate symptoms, that could be very impactful, and that concerns me\u003c/em\u003e\u0026rdquo; (03\u0026ndash;008). Half (n\u0026thinsp;=\u0026thinsp;5; 50%) of the participants reported that they would need assistance with doing daily tasks like driving and feeding themselves.\u003c/p\u003e \u003cp\u003eSixteen (94%) participants selected a response option between \u0026ldquo;very mild\u0026rdquo; and \u0026ldquo;moderate.\u0026rdquo; All participants were asked to describe what they imagined symptoms and impacts would be like at a severe level. Responses to how symptoms would be experienced at a \u0026ldquo;severe\u0026rdquo; state were varied. Ten of the 16 participants (63%) spoke of a loss of mobility and 4 (25%) spoke of needing a walker or wheelchair. Six (38%) participants conceptualized \u0026ldquo;severe\u0026rdquo; to mean needing a full-time caregiver to assist with their needs. For example, 1 participant summarizes what they believe a \u0026ldquo;severe\u0026rdquo; state of symptoms could be as follows:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e \u003cem\u003eI think the shaking will be worse. I think walking will be impaired. I think the memory will be slower. Balance would be affected\u0026hellip;It would completely change my life because it would be less mobility\u003c/em\u003e (01\u0026ndash;005)\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eFinally, all participants (n\u0026thinsp;=\u0026thinsp;17) were asked to describe what they expected the severity of symptoms would be and how those symptoms would impact their day-to-day life for \u0026ldquo;very severe.\u0026rdquo; Participants\u0026rsquo; descriptions continued to increase in severity around being in a state of immobility and in need of a wheelchair due to their inability to walk on their own (n\u0026thinsp;=\u0026thinsp;11; 65%). Eight participants (47%) also mentioned the need for a constant caregiver or the need to be admitted to a full-time healthcare facility (n\u0026thinsp;=\u0026thinsp;3;18%) at this level of severity.\u003c/p\u003e \u003cp\u003eOne participant summed up their hypothetical summary of \u0026ldquo;very severe\u0026rdquo; as follows:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e \u003cem\u003eI will probably have to live with somebody\u0026hellip;somebody feeding me and helping bathe me and all the other\u0026hellip; I could be close to bedridden\u0026hellip; if it\u0026rsquo;s very severe and working would be non-existent.\u003c/em\u003e (01\u0026ndash;003)\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;7\u003c/b\u003e provides a summary of PGI-S (ESM 2).\u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eIn this study, we sought to understand the symptoms and impacts experienced by an early-stage Parkinson\u0026rsquo;s population. Additionally, we investigated perceived thoughts on progression of disease at different severity levels with the PGI-S providing a well-defined framework for the concept of severity.\u003c/p\u003e \u003cp\u003eThere have been many notable advances in detection and assessment of Parkinson\u0026rsquo;s over the last several years [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], despite these advancements researchers must be mindful that disease severity and impacts are highly personal and most accurately assessed through the evaluation of personal experience.\u003c/p\u003e \u003cp\u003eObtaining the personal disease journey of these 17 participants at the early stages of Parkinson\u0026rsquo;s furnished insight into how early-stage Parkinson's is experienced, which is a sub-group of patients few other studies have investigated. Participants shared their symptom severity experiences, and how living in the early stages impacts their lives. As part of the eligibility requirements to participate in this study, we designed the recruitment to be limited to participants who had lower scores on the mH\u0026amp;Y scale. While mH\u0026amp;Y scoring requirements of 1.0\u0026ndash;2.5 provided more limitations in our recruitment strategy, it ensured that the data on severity was captured in a population who were early in their disease experience.\u003c/p\u003e \u003cp\u003eInterestingly, when these early-stage participants were asked to rate their severity over the past 7 days using the scale, 35% stated their symptoms to be at a \u0026ldquo;moderate\u0026rdquo; level. Similar to the current literature [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], which confirms tremors as the most bothersome symptom, nearly every participant (n\u0026thinsp;=\u0026thinsp;16; 94%) in this study reported tremors as the key symptom in their early stages. For individuals living with early onset PD symptoms, there was associated shame and embarrassment that was frequently so strong it caused individuals to isolate and withdraw from social and family events, highlighting that severity is not always dependent upon a disease\u0026rsquo;s advancement and the severity of a symptom can also be evaluated as severe because of the personal, lived experience.\u003c/p\u003e \u003cp\u003eThe qualitative interviews conducted in our study also demonstrate concerns about symptom discrimination in the workplace, changes in interpersonal relationships, and misperceptions of being drunk because of the shaking and tremors that Parkinson\u0026rsquo;s causes. These impacts were shared as significant to the early stages of the disease. Several participants mentioned feelings of depression, which has been identified previously as having the biggest impact on patients\u0026rsquo; lives [\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The stories shared in our study provide further insight into how the struggles with this disease may exacerbate symptoms of depression and more awareness of this even at an early-onset stage may help with the management of these patients.\u003c/p\u003e \u003cp\u003eThe cognitive debriefing exercise conducted using the PGI-S response options demonstrates the comprehensiveness of the measure in an early-stage population. None of the participants had issues with comprehending the items or response options in the measure and they could easily reflect on their current and hypothesized future states of symptom severity. While the PGI-S is a global measure generally used to rate the severity of a specific condition rather than a phase of a disease like the early stages of Parkinson\u0026rsquo;s, these findings show that the measure may be useful for future research wanting to look at changes in the severity.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Limitations\u003c/h2\u003e \u003cp\u003eAlthough 17 participants are generally considered a small sample size limitation, it is within the acceptable range of recruitment for similar qualitative studies [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Concept validity was considered achieved with as no new concepts were emerging in the dataset after 13 interviews. Evidence suggests that with a qualitative sample size of n\u0026thinsp;=\u0026thinsp;15, researchers should reasonably expect to elicit more than 90% of concepts being elicited through n\u0026thinsp;=\u0026thinsp;20 interviews [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. While every effort was made to recruit a minimum of N\u0026thinsp;=\u0026thinsp;20, our study\u0026rsquo;s eligibility criteria presented some challenges with recruiting participants who were treatment na\u0026iuml;ve or had started monotherapy with an anti-Parkinson medication within 3 years of screening for this study. Furthermore, sample sizes for cognitive debriefing studies vary upon the complexity of the measure and diversity of the patient population. Some studies have even suggested samples as small as 7 to 10 are sufficient [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Because the PGI-S is a global measure and the question is relatively simple, a sample of 17 participants is considered reasonable to gather information about the relevance of the severity categories and information about severity progression along the severity continuum of the measure within this population. Additional limitations included a wider range of modified Hoehn and Yahr stages (1-2.5) as this study had initially sought to mirror a clinical trial closed, and the data was repurposed for this manuscript. There are significant symptom changes that can appear from stage 1 to stage 2 that impact quality of life. At stage 1-1.5 (n\u0026thinsp;=\u0026thinsp;13; 76%) a person generally has mild unilateral symptoms that typically don\u0026rsquo;t interfere with daily activity. As the disease progresses to stage 2-2.5 (n\u0026thinsp;=\u0026thinsp;4; 24%) symptoms begin to that was get worse and appear bilaterally which makes daily tasks more difficult and may require the person to seek assistance from a caregiver. However, the early stages of Parkinson\u0026rsquo;s experience can vary widely due to the heterogeneous presentation of the disease [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough this research was limited by an older population of participants with co-occurring chronic conditions (the mean age of participants was 61.6, receiving anti-Parkinson medication [n\u0026thinsp;=\u0026thinsp;13; 76%]), the study sample age range and mean age was similar to recently published research [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Yet, due to the limited literature in younger populations, more research should be conducted within a younger, treatment na\u0026iuml;ve, early-stage population with fewer comorbidities. And, finally, while every effort was made to obtain a more diverse dataset, participants were disproportionately non-Hispanic, white males with a high-school education or higher. The heterogeneity of this dataset is in alignment with the demographics of an early diagnosed population in the US [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], and a recent publication that included an early-stage population [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. A more diverse sample is recommended in future research to address the current racial disparities existing among movement disorder diagnoses [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eWhile many studies have sought to understand the vast and varied impact of Parkinson\u0026rsquo;s, the population at the early stage experience of disease severity has been understudied. This study highlights that even at the early stages of the disease, individuals living with Parkinson\u0026rsquo;s experience a wide range of symptoms and associated impacts which shape their day-to-day experience and contribute to their perception of their severity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding: No funding was received for conducting this study.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCOI Statement:\u0026nbsp;\u003c/strong\u003eAuthors AS, CDR, CUF and TS are employed by Clinical Outcomes Solutions.\u0026nbsp;The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Clinical Outcome Solutions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics:\u0026nbsp;\u003c/strong\u003eThe study protocol was reviewed and approved by the\u0026nbsp;Western Institutional Review Board-Copernicus Group (WCG IRB Study #1334453; IRB Tracking #20222833), and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate and Consent to Publish\u003c/strong\u003e: Informed consent was obtained from all individual participants included in the study. The authors affirm that human research participants provided informed consent for publication of\u0026nbsp;collected data for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u0026nbsp;\u003c/strong\u003eAW, CD, and TS conceptualized and designed this study, and approved the final protocol. AS, CUF, and CDR conducted the interviews and analyzed the data. All authors interpreted the data and read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eMedical writing and editorial assistance, under the authors\u0026rsquo; guidance and funded by Kyowa Kirin, was provided by Emily Calderbank, MA (Clinical Outcomes Solutions, Chicago, USA) and David Navarro, BS (Clinical Outcomes Solutions, Tucson, AZ, USA).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBloem BR, Okun MS, Klein C. Parkinson's disease. 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Patient Related Outcome Measures. 2019:141\u0026ndash;152.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eL\u0026ouml;hle M, Bremer A, Gandor F, et al. Validation of the PD home diary for assessment of motor fluctuations in advanced Parkinson\u0026rsquo;s disease. npj Parkinson's Disease. 2022;8(1):69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrancis JJ, Johnston M, Robertson C, et al. What is an adequate sample size? Operationalising data saturation for theory-based interview studies. Psychology and health. 2010;25(10):1229\u0026ndash;1245.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang Y, Yuan Y, Zhang G, et al. Artificial intelligence-enabled detection and assessment of Parkinson\u0026rsquo;s disease using nocturnal breathing signals. Nature medicine. 2022;28(10):2207\u0026ndash;2215.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhn S, Springer K, Gibson JS. Social withdrawal in Parkinson's disease: A scoping review. Geriatric Nursing. 2022;48:251\u0026ndash;261.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcKinlay A, Grace R, Dalrymple-Alford J, Anderson T, Fink J, Roger D. A profile of neuropsychiatric problems and their relationship to quality of life for Parkinson's disease patients without dementia. Parkinsonism \u0026amp; related disorders. 2008;14(1):37\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoh S-E, Morris ME, McGinley JL. Determinants of health-related quality of life in Parkinson\u0026rsquo;s disease: a systematic review. Parkinsonism \u0026amp; related disorders. 2011;17(1):1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHennink MM, Kaiser BN, Marconi VC. Code saturation versus meaning saturation: how many interviews are enough? Qualitative health research. 2017;27(4):591\u0026ndash;608.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRothman M, Burke L, Erickson P, Leidy NK, Patrick DL, Petrie CD. Use of existing patient-reported outcome (PRO) instruments and their modification: the ISPOR Good Research Practices for Evaluating and Documenting Content Validity for the Use of Existing Instruments and Their Modification PRO Task Force Report. Value in Health. 2009;12(8):1075\u0026ndash;1083.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWillis GB. \u003cem\u003eCognitive interviewing: A tool for improving questionnaire design\u003c/em\u003e. sage publications; 2004.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParkinson's Foundation. Stages of Parkinson's. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.parkinson.org/understanding-parkinsons/what-is-parkinsons/stages\u003c/span\u003e\u003cspan address=\"https://www.parkinson.org/understanding-parkinsons/what-is-parkinsons/stages\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeal LS, Andrae DA, Myers DE, Johnson N, Foster B, Evans CJ. The Measurement Performance of the Parkinson's Disease Activities of Daily Living, Interference, and Dependence Instrument. Frontiers in Neurology. 2022;13:760174.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDahodwala N, Siderowf A, Xie M, Noll E, Stern M, Mandell DS. Racial differences in the diagnosis of Parkinson's disease. Movement Disorders. 2009;24(8):1200\u0026ndash;1205.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNwabuobi L, Agee J, Gilbert R. Racial and social disparities in health and health care delivery among patients with parkinson\u0026rsquo;s disease and related disorders in a multiracial clinical setting. Journal of Cross-Cultural Gerontology. 2021;36(3):253\u0026ndash;263.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 to 7 are available in the Supplementary Files section.\u003c/p\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":"","lastPublishedDoi":"10.21203/rs.3.rs-4731346/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4731346/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlthough Parkinson’s Disease is the second most common neurodegenerative disease, the lived experience of individuals with early-stage Parkinson’s has not received much attention. This study sought to understand how the spectrum of severity is described and perceived by this population using the Patient-Global Impressions of Severity scale. Additionally, early-stage Parkinson’s patients described what symptoms and quality of life impacts were most important to the early stages of the Parkinson’s experience.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, 17 participants with early-stage Parkinson’s (1-2.5 on the modified Hoehn and Yahr scale) were interviewed about their experience with Parkinson’s as well as cognitively debriefed on the Patient Global Impressions of Severity scale. Analysis was performed using NVivo 13 a qualitative analysis software.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMost participants reported tremors as their most bothersome symptom and the impact to their daily lives was most disruptive. Nearly every participant spoke about the emotional burden of their Parkinson’s diagnosis. Contemplating the future of their disease had a significant impact, which several said caused them to experience anxiety and/or depression. Participants were also able to describe the spectrum of severity for Parkinson’s and its quality of life impact, including severity levels they have not yet reached, using the global severity scale.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study highlights that even at the early stages of the disease, individuals living with Parkinson’s experience a wide range of symptoms and related quality of life impacts which shape their daily experience and contribute to perceptions of severity.\u003c/p\u003e","manuscriptTitle":"A Qualitative Study Exploring Patient Global Impression of Disease Severity in Early Stages of Parkinson’s Disease.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-28 02:26:11","doi":"10.21203/rs.3.rs-4731346/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":"96b8b441-7676-41dc-8489-da9b5cf2c4e5","owner":[],"postedDate":"August 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-09T16:24:13+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-28 02:26:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4731346","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4731346","identity":"rs-4731346","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}