Patient-Centered Drug Development in Rare Diseases: The Case of Duchenne Muscular Dystrophy

Problem Statement Patient-centeredness has gained favor in recent years. Drug development researchers increasingly acknowledge that patient preferences can contribute valuable information to decision-making. The importance of incorporating patient preferences is underscored for rare disease populations in which clinicians and researchers have limited experience with the condition and the disease experience is best understood by patients. This dissertation aims to measure preferences among caregivers and patients with Duchenne muscular dystrophy (DMD). Methods This body of work is based on a two online surveys intended for caregivers and patients with DMD. Survey respondents were recruited via a patient registry and snowball sampling. The surveys were designed using a community-engaged approach and included best-worst scaling (BWS) case 1, case 2 and conjoint-analysis. The main analytic methods included latent class analysis, mixed logistic regression and conditional logistic regression. Results Chapter 3 demonstrates a successful process for community engagement in survey development that affected eligibility criteria, attribute refinement, and revealed the delicate nature of mapping clinical trial endpoints to meaningful survey objects. Chapter 4 findings indicate that caregivers and patients do not differ in their prior- ities for signs and symptoms to be targeted by therapeutic interventions. However, priority heterogeneity does exist and may be related to unobserved characteristics. Chapter 5 findings reveal patients are willing to accept significant risk in order to have the benefit of moderate improvements in pulmonary decline. Finally, methodological findings in Chapter 6 indicate that conjoint analysis combined with BWS provides policy-relevant information about the intention to use therapy and serves to validate the BWS method. Conclusions This research contributes to the overall body of knowledge around patient preferences in DMD and as a result may improve the usefulness of future drug development. It also measures patient preferences for a pulmonary benefit, information that will be incorporated into regulatory review. There are implications for the broader rare disease community: this dissertation demonstrates a model for how to undergo this research and underscores the importance of preference work to meet the unique needs of the rare disease community

Seeing is Engaging: Vlogs as a Tool for Patient Engagement

Video blogs (‘vlogs’ – pronounced as one syllable) are a popular platform for conveying know-how online and can be used as a tool for patient engagement. It can be challenging to engage patients in their own care, and the unique attributes of vlogs overcome some of the barriers to engagement such as high treatment burden and a lack of the sense of community. While some clinicians may distrust social media and question its place in patient care, we present The Frey Life, one example of a patient vlog, to show how the platform models and fosters engagement, and provides the patient perspective. We discuss potential concerns regarding health vlogs, and suggest implications for physicians, researchers, and medical institutions regarding how to use patient vlogs as a resource

Screening Parents During Child Evaluations: Exploring Parent and Child Psychopathology in the Same Clinic

Objective: Children of depressed and/or anxious parents are at increased risk for developing psychiatric disorders. Little research has focused on screening parents bringing their children for psychiatric evaluation, and few studies have included fathers or Hispanic children. This study had the following aims: 1) to identify current symptom rates in parents bringing their children for evaluation; and 2) to determine whether parental symptoms were associated with children\u27s symptoms, diagnoses, and functioning. Method: The sample included 801 mothers, 182 fathers, and 848 children (aged 6 through 17 years). The majority (55.66%) were Hispanic, who attended a child and adolescent psychiatric evaluation service. Parent and child symptoms were assessed via parental reports. Children\u27s diagnoses and functioning were determined by clinicians. Multiple regression analyses were used to determine whether severity of parental symptoms was associated with clinical child variables adjusting for child and parent demographic variables. Results: In all, 18.80% of mothers and 18.42% of fathers reported elevated internalizing symptoms. Maternal symptoms were significantly associated with problems in children\u27s functioning and children\u27s anxiety, depression, and oppositional/conduct diagnoses; but not attention-deficit/hyperactivity disorder. Adjusting for parental and child demographics had a reduction on the effect of maternal symptoms on child depression. Paternal symptoms and functioning were positively associated with children\u27s diagnoses, but the associations were smaller and not significant. Both parents\u27 symptoms were significantly associated with children\u27s internalizing and externalizing symptoms. However, these significant effects were not moderated by marital status or child ethnicity. Conclusions: This study highlights the importance of screening parents when their children receive a psychiatric evaluation. The findings support the development of mental health services that address psychiatric needs of the entire family within one clinical setting

Using Best–Worst Scaling to Investigate Preferences in Health Care

Introduction Best–worst scaling (BWS) is becoming increasingly popular to elicit preferences in health care. However, little is known about current practice and trends in the use of BWS in health care. This study aimed to identify, review and critically appraise BWS in health care, and to identify trends over time in key aspects of BWS. Methods A systematic review was conducted, using Medline (via Pubmed) and EMBASE to identify all English-language BWS studies published up until April 2016. Using a predefined extraction form, two reviewers independently selected articles and critically appraised the study quality, using the Purpose, Respondents, Explanation, Findings, Significance (PREFS) checklist. Trends over time periods (≤2010, 2011, 2012, 2013, 2014 and 2015) were assessed further. Results A total of 62 BWS studies were identified, of which 26 were BWS object case studies, 29 were BWS profile case studies and seven were BWS multi-profile case studies. About two thirds of the studies were performed in the last 2 years. Decreasing sample sizes and decreasing numbers of factors in BWS object case studies, as well as use of less complicated analytical methods, were observed in recent studies. The quality of the BWS studies was generally acceptable according to the PREFS checklist, except that most studies did not indicate whether the responders were similar to the non-responders. Conclusion Use of BWS object case and BWS profile case has drastically increased in health care, especially in the last 2 years. In contrast with previous discrete-choice experiment reviews, there is increasing use of less sophisticated analytical methods