Understanding dentatorubral-pallidoluysian atrophy (DRPLA) symptoms and impacts on daily life: a qualitative interview study with patients and caregivers.

Background: Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, neurodegenerative disorder with no disease-modifying treatments. There is a dearth of information in the literature about the patient and caregiver experience living with DRPLA. Objectives: This study aimed to (1) understand symptoms experienced by adult- and juvenile-onset DRPLA populations and their impact on daily life and (2) explore patient and caregiver treatment goals and clinical trial participation preferences. Design: The study was a qualitative interview study. Methods: Interviews were conducted remotely with adult patients with DRPLA and caregivers. Participants described patient symptoms and the impact of those symptoms on daily life, and they discussed treatment goals and potential clinical trial participation. There were 18 patients described in the interviews with two patients and seven caregivers. Some participants were caregivers to multiple patients with DRPLA. Results: Interview transcripts were coded for themes, and reported symptoms were summarized with descriptive statistics. Adult-onset patients (N = 7) experienced difficulty with ataxia (100%), cognition (100%), fine motor skills (100%), gross motor skills (100%), speech (100%), personality changes (100%), and seizures (57%). Juvenile-onset patients (N = 11) experienced difficulty with ataxia (100%), sleep (100%), speech (100%), jerking/twitching (83%), behavior (82%), cognition (82%), fine motor skills (82%), gross motor skills (82%), sensory sensitivity (75%), and seizures (64%). When considering aspects of DRPLA to target for future treatment, patients prioritized ataxia/mobility (100%), juvenile-onset caregivers prioritized ataxia/mobility (60%) and independence (60%), and adult-onset caregivers prioritized personality (60%). Almost all patients (93%) would participate in a clinical trial if given the opportunity, but travel to a clinical site could pose a participation barrier for half. Conclusion: This study found that there are symptom domains that are relevant across the DRPLA population, but there is heterogeneity within each domain based on the age of symptom onset and disease stage, which has implications for clinical trial design.

Understanding dentatorubral-pallidoluysian atrophy (DRPLA) symptoms and impacts on daily life through interviews with patients and caregivers Why was the study done? Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare and progressive brain disorder. Little is known about the patient and caregiver experience living with DRPLA and this lack of information has hindered the development of patient-focused treatments and the measurement of outcomes that are most meaningful to caregivers and patients. What did the researchers do? To address this problem, researchers conducted interviews with patients and caregivers of DRPLA to (1) better understand symptoms experienced by adult- and juvenile-onset DRPLA populations and their impact on daily life and (2) explore patient and caregiver treatment goals and clinical trial participation preferences. What did the researchers find? Eighteen patients were described in the interviews. Adult-onset patients (onset at age 20 or older) experienced difficulty with coordination, cognition, motor skills, speech, personality changes, and seizures. Juvenile-onset patients (onset before age 20) experienced difficulty with coordination, sleep, speech, jerking/twitching, behavior, cognition, motor skills, sensory sensitivity, and seizures. When considering symptoms to prioritize for future treatment, patients and caregivers identified coordination/mobility, independence, and personality as important. Nearly all participants indicated they would participate in a clinical trial if given an opportunity, however half expressed that travel to a clinical site could pose a barrier. What do the findings mean? This study provides a better understanding of the symptoms experienced by DRPLA patients and their impact on daily life. Additionally, it identifies important targets for treatment and considerations when designing clinical trials for DRPLA such as the barrier caused by travel to a clinical site.

Home-based video assessment of ease of movement for patients with Duchenne: Interviews with physical therapists to select movement tasks.

BACKGROUND AND PURPOSE: Patients with Duchenne muscular dystrophy (DMD) change their movement patterns to compensate for muscle weakness. The Duchenne Video Assessment (DVA) measures ease of movement through evaluation of compensatory movements. The DVA directs caregivers to video record patients performing home-based movement tasks using a mobile application, and DVA-certified physical therapists evaluate the videos using scorecards with prespecified compensatory movement criteria. Two qualitative interview studies were conducted to select movement tasks for the DVA that are relevant to patients with DMD and able to reflect changes in function. METHODS: Qualitative interviews with eligible physical therapists were conducted remotely. Physical therapists were asked to spontaneously suggest movement tasks prior to evaluating specific movement tasks selected a priori. Analysts conducted a content analysis to investigate whether movement tasks selected a priori were confirmed as relevant to the population of interest and able to show changes in function. RESULTS: The studies included five physical therapists to select tasks for ambulatory patients with DMD and six for non-ambulatory patients. For an ambulatory population, all five experts confirmed Climb Five Stairs, Run, Stand Up from Sitting, Sit Up from Supine, and Jump Forward, and four (80%) confirmed Walk as relevant and able to show functional changes. For a non-ambulatory population, all six experts confirmed Eat 10 Bites, Roll Over in Bed, Shift Weight in Bed, Take T-Shirt Off, Put T-Shirt On, Put Arms on Armrest, and Reach Across Table to Grab Cell Phone, and five (83%) confirmed Raise Hands Above Head as relevant and able to show functional changes. DISCUSSION: Physical therapists confirmed the DVA movement tasks as relevant to patients with DMD and able to reflect changes in function. The use of the DVA in clinical trials provides an opportunity to collect data not seen in clinic and reduce travel burden for families.

Development of Duchenne Video Assessment scorecards to evaluate ease of movement among those with Duchenne muscular dystrophy.

BACKGROUND: Patients with Duchenne muscular dystrophy (DMD) adopt compensatory movement patterns as muscles weaken. The Duchenne Video Assessment (DVA) measures patient ease of movement through identification of compensatory movement patterns. The DVA directs caregivers to video record patients performing specific movement tasks at home using a secure mobile application, and DVA-certified physical therapists (PTs) score the videos using scorecards with prespecified compensatory movement criteria. The goal of this study was to develop and refine the DVA scorecards. METHODS: To develop the initial scorecards, 4 PTs collaboratively created compensatory movement lists for each task, and researchers structured the lists into scorecards. A 2-round modified Delphi process was used to gather expert opinion on the understandability, comprehensiveness, and clinical meaningfulness of the compensatory movements on the scorecards. Eight PTs who had evaluated ≥50 patients with DMD and participated in ≥10 DMD clinical trials were recruited for the panel. In Round 1, panelists evaluated compensatory movement criteria understandability via questionnaire and tested the scorecards. In Round 2, panelists participated in an in-person meeting to discuss areas of disagreement from Round 1 and reach consensus (≥75% agreement) on all revisions to the scorecards. RESULTS: During the Round 1 revisions to the scorecards, there were 67 changes (44%) to the wording of 153 original compensatory movement criteria and 3 criteria were removed. During the Round 2 revisions to the scorecards, there were 47 changes (31%) to the wording of 150 compensatory movement criteria, 20 criteria were added, and 30 criteria were removed. The panel reached 100% agreement on all changes made to scorecards during Round 2. CONCLUSION: PTs with extensive experience evaluating patients with DMD confirmed that the compensatory movement criteria included in the DVA scorecards were understandable, comprehensive, and clinically meaningful.

Reliability and construct validity of the Duchenne Video Assessment.

INTRODUCTION: The Duchenne Video Assessment (DVA) assesses quality of movement as an indication of Duchenne muscular dystrophy (DMD) disease severity. Caregivers video record patients performing home-based movement tasks using a mobile application, and physical therapists (PTs) rate the videos using scorecards with prespecified compensatory movement criteria. Reliability and construct validity of the DVA were tested using video and Pediatric Outcomes Data Collection Instrument (PODCI) data from patients with DMD and healthy controls from a separate study. METHODS: Fifteen PTs were trained and certified as DVA raters. All raters scored videos of five subjects performing each movement task; nine raters rescored the same videos four weeks later. Three raters scored videos from an average of 25 subjects for each movement task. Aggregate scores were used to test construct validity. An expert DMD clinician assigned each video to a severity group for known-groups analyses. Differences between rater scores across severity groups were tested and correlations between DVA and PODCI scores were calculated. RESULTS: Inter-rater reliability (intraclass correlation coefficient [ICC]) between all 15 raters ranged from 0.70 to 0.97 for all movement tasks. Mean intra-rater reliability ICC for nine raters ranged from 0.82 to 0.98 for all movement tasks. There were statistically significant differences between known severity groups for all movement tasks. The DVA correlated strongly with related PODCI constructs of physical function and weakly with unrelated constructs. DISCUSSION: The DVA was found to be a reliable and valid tool for measuring quality of movement as an indication of disease severity.

Factors Associated With Poor Linkage to Human Immunodeficiency Virus Care Among Index Clients and Sex Partners Receiving Human Immunodeficiency Virus Assisted Partner Services in Kenya.

INTRODUCTION: Human immunodeficiency virus (HIV) assisted partner services (aPS) has been recommended as a strategy to increase HIV case finding. We evaluated factors associated with poor linkage to HIV care among newly diagnosed HIV-positive individuals (index clients) and their partners after receiving aPS in Kenya. METHODS: In a cluster randomized trial conducted between 2013 and 2015, 9 facilities were randomized to immediate aPS (intervention). Linkage to care-defined as HIV clinic registration, and antiretroviral therapy (ART) initiation were self-reported. Antiretroviral therapy was only offered to those with CD4 less than 500 during this period. We estimated linkage to care and ART initiation separately for index clients and their partners using log-binomial generalized estimating equation models with exchangeable correlation structure and robust standard errors. RESULTS: Overall, 550 index clients and 621 sex partners enrolled, of whom 46% (284 of 621) were HIV-positive. Of the 284, 264 (93%) sex partners returned at 6 weeks: 120 newly diagnosed and 144 whom had known HIV-positive status. Among the 120 newly diagnosed, only 69% (83) linked to care at 6 weeks, whereas among the 18 known HIV-positive sex partners not already in care at baseline, 61% (11) linked. Newly diagnosed HIV-positive sex partners who were younger and single were less likely to link to care (P < 0.05 for all). CONCLUSION: Only two thirds of newly diagnosed, and known HIV-positive sex partners not in care linked to care after receiving aPS. The HIV aPS programs should optimize HIV care for newly diagnosed HIV-positive sex partners, especially those who are younger and single.

Index participant characteristics and HIV assisted partner services efficacy in Kenya: results of a cluster randomized trial.

INTRODUCTION: We have previously demonstrated that assisted partner services (aPS) increases HIV testing and case finding among partners of persons living with HIV (PLHIV) in a cluster randomized trial in Kenya. However, the efficacy of aPS may vary across populations. In this analysis, we explore differences in aPS efficacy by characteristics of index participants. METHODS: Eighteen HIV testing sites were randomized to immediate versus 6-week delayed aPS. Participants were PLHIV (or index participants) and their sexual partners. Partners of index participants were contacted for HIV testing and linked to care if HIV positive. Primary outcomes were the number of partners per index participant who: 1) tested for HIV, 2) tested HIV positive and 3) enrolled in HIV care. We used generalized estimating equations to assess differences in aPS efficacy by region, testing location, gender, age and knowledge of HIV status. RESULTS: From 2013 to 2015, the study enrolled 1119 index participants, 625 of whom were in the immediate group. These index participants named 1286 sexual partners. Immediate aPS was more efficacious than delayed aPS in promoting HIV testing among partners in high compared to low HIV prevalence regions (Nyanza incidence rate ratio (IRR) 7.2; 95% confidence interval (CI) 5.4, 9.6 vs. Nairobi/Central IRR 3.4 95% CI 2.3, 4.8). Higher rates of partner HIV testing were also observed for index participants in rural/peri-urban compared to urban sites (IRR 6.6; 95% CI 4.5, 9.6 vs. IRR 3.5 95% CI 2.5, 5.0 respectively), for female versus male index participants (IRR 5.8 95% CI 4.2, 7.9 vs. IRR 3.7; 95% CI 2.4, 5.8 respectively) and for newly diagnosed versus known HIV-positive index participants (IRR 6.0 95% CI 4.2, 8.7 vs. IRR 3.3; 95% CI 2.0, 7.7 respectively). Providing aPS to female versus male index participants also had a significantly higher HIV case finding rate (IRR 9.1; 95% CI 4.0, 20.9 vs. IRR 3.2 95% CI 1.7, 6.0 respectively.) CONCLUSIONS: While it is known that aPS promotes increases in HIV testing and case finding, this is the first study to demonstrate significant differences in aPS efficacy across characteristics of the index participant. Understanding these differences and their drivers will be critical as aPS is brought to scale in order to ensure all PLHIV have access to these services.

The Case for the Use of Patient and Caregiver Perception of Change Assessments in Rare Disease Clinical Trials: A Methodologic Overview.

INTRODUCTION: The traditional model of evaluating treatments based primarily on primary outcome measures has stumbled in its application to rare disease. Rare disease clinical trials face the methodological challenges of small, heterogeneous patient populations and relatively few validated, disease-specific outcome measures. Incorporating qualitative research into rare disease clinical trials may help sponsors, regulators, payers, and prescribers to better understand the real-world and patient-specific impact of a potential therapy. This paper provides a methodologic overview of the use of Patient and Caregiver Perception of Change (PPC and CPC) Assessments utilizing patient and caregiver video interviews to complement the data captured by traditional endpoints in rare disease clinical trials. METHODS: Incorporating qualitative patient and caregiver video interviews into clinical trials allows for the rigorous capture of patient experiences and caregiver observations. Interview guides informed by input from key stakeholders provide the opportunity to solicit structured feedback on experiences before, during, and after the clinical trial. Patients and caregivers can complete their video interviews in a study mobile application, and interview transcripts are analyzed by independent coders. Themes are summarized by the treatment group and individual patient, which adds context to the clinical outcome measures of how patients feel and function, as well as elucidates the degree of change that is meaningful to patients and caregivers. The qualitative results can be compared to the data captured in clinical trials to assess data concordance. CONCLUSION: Capturing patient experience data with sufficient rigor allows it to contribute to the body of evidence utilized in regulatory, payer, and prescriber decision-making. Adding PPC and CPC Assessments to rare disease clinical trials offers an innovative and powerful way to tap into the unique insights of patients and their families to develop a fuller picture of the patient experience in the clinical trial. FUNDING: Stealth BioTherapeutics Inc.