External Advisory Committee Research Articles

Maximizing the Value of Real-World Data and Real-World Evidence to Accelerate Healthcare Transformation in China: Summary of External Advisory Committee Meetings.

Use of real-world data (RWD) is gaining wide attention. To bridge the gap between diverse healthcare stakeholders and to leverage the impact of Chinese real-world evidence (RWE) globally, a multi-stakeholder External Advisory Committee (EAC) and EAC meetings were initiated, aiming to elucidate the current and evolving RWD landscape in China, articulate the values of RWE in ensuring Chinese patients' equitable access to affordable medicines and solutions, and identify strategic opportunities and partnerships for expansion of RWE generation in China. Chinese and international experts who are clinicians and academic researchers were selected as EAC members based on their professional background and familiarity with RWD/RWE. Three EAC meetings were held quarterly in 2023. Various topics were presented and discussed for insights and suggestions. Nine experts from China, one from South Korea, and two from Europe were selected as EAC members and attended these meetings. Experts' presentations were summarized by theme, including the RWD landscape and RWE enablement in China, as well as global development of a patient-centric ecosystem. Experts' insights and suggestions on maximizing the RWD/RWE value to accelerate healthcare transformation in China were collected. We concluded that though data access, sharing, and quality are still challenging, RWD is developing to support evidence generation in the medicinal product lifecycle, inform clinical practice, and empower patient management in China. RWD/RWE creates value, accelerates healthcare transformation, and improves patient outcomes. Fostering a patient-centric ecosystem across healthcare stakeholders and maintaining global partnerships and collaboration are essential for unlocking the power of RWD/RWE.

Optimizing external advisory committee meetings of Clinical and Translational Science Awards through focused pre-review.

External advisory committees (EACs) are critical peer-review meetings that drive improvement at Clinical and Translational Science Award Program Hubs. Despite their ubiquity, evaluations of EAC optimization and effective implementation remain scarce. We present a two-tiered approach to optimizing EAC meetings through (1) in-depth, topically focused "pre-review" meetings comprised of external topic experts and at least one standing "full-board" EAC member, followed by (2) a traditional "full-board" EAC meeting. This approach allowed pre-review discussion of program-focused topics and specific recommendations, later delivered to the full-board for review and direction. To evaluate this approach, we interviewed 18 people who planned, administered, or attended pre-review and/or full-board meetings, including internal Hub staff, external topic experts, and standing EAC members. Thematic analysis was used to explore planning, implementation, and value of our two-tiered approach versus the traditional single full-board approach. Interviewees preferred the two-tiered approach, noting benefits including additional time to reflect, shared identification of strengths and challenges, and discussion of solutions to share later with the full-board. Those who attended pre-review meetings described building "transformational," rather than "transactional," relationships with invitees through more discussion and inter-hub sharing. That increased sharing invited more exploration, discussion, and planning of next steps toward innovation.

The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence.

The U.S. Food and Drug Administration (FDA) approved eteplirsen (Exondys 51) for Duchenne muscular dystrophy in 2016 via its accelerated approval program on the basis of a study of 12 boys. After a contentious review process and a high-profile meeting of an external advisory committee, FDA leaders concluded that very small increases in treated patients' levels of dystrophin, a muscle protein, were reasonably likely to predict clinical benefit. The eteplirsen approval, which was followed by approvals of other drugs in the same class via the same pathway, has been controversial because of the questionable evidence underlying these decisions, delays in mandated postapproval testing, and high U.S. prices. Questions remain about the effectiveness and long-term safety of these products. Although the FDA initially set a November 2020 deadline for eteplirsen's manufacturer to complete a clinical trial determining whether the drug has clinical benefit, the company will not complete the trial until 2024 or later. The relationship between levels of truncated dystrophin, the muscle protein studied in eteplirsen's pivotal trial, and clinical outcomes remains uncertain. Despite recent legislative and regulatory changes to the FDA's accelerated approval pathway, the history of eteplirsen and similar drugs points to the need for additional reforms to better balance evidence generation with patient safety and access to promising medications. Lawmakers and regulators should take further action to limit excessive spending on unproven therapies and ensure that drug sponsors conduct robust and timely confirmatory trials after receiving accelerated approval.

Depression and Dementia Risk: A Population-Based Cohort Study in Denmark (P2-6.008)

<h3>Objective:</h3> Examine the relation between depression and incident dementia in Denmark. <h3>Background:</h3> Depressive symptoms often precede onset of dementia, but prior research reports diminished or null associations with increasing time since depression diagnosis. The absence of an association between remote depression diagnosis and incident dementia suggests depression is an early symptom rather than a cause of dementia. <h3>Design/Methods:</h3> This nationwide population-based cohort study leverages data collected routinely and prospectively from Danish population-based registries from 1978–2018. Individuals with depression ages ≥18 years were matched with members of the general population on sex, birth year, and date of depression diagnosis. Using Cox proportional hazards regression models, we estimated hazard ratios (HR) for the association between depression and dementia. To characterize the relationship between depression and dementia, all analyses were stratified by time elapsed between diagnoses (1–10 years; &gt;10–20 years; &gt;20–39 years). Because risk of depression and dementia may differ by age and sex, we conducted separate analyses for men and women and by age category. <h3>Results:</h3> Among 246,499 persons with depressive disorders and 1,190,302 matched persons, depression was associated with more than double the hazard of dementia (HR=2.43; 95% confidence interval [CI]: 2.37, 2.49). This HR was largest within the first 10 years after depression diagnosis (HR=2.60, 95% CI: 2.53, 2.68), but persisted &gt;10–20 years (HR=1.89, 95% CI: 1.79, 2.01) and &gt;20–39 years (HR=1.80, 95% CI: 1.59, 2.04). The association between depression and dementia was stronger among men (HR=3.02, 95% CI: 2.88, 3.16) than women (HR=2.22, 95% CI: 2.16, 2.29), and strongest among individuals diagnosed with depression between ages 18–44 (HR=3.09, 95% CI: 2.66, 3.60). <h3>Conclusions:</h3> This study demonstrates a robust association between incident depression and subsequent dementia when the diagnoses are separated by more than two decades, and thus suggests a role for depression as a major risk factor. <b>Disclosure:</b> Dr. Elser has nothing to disclose. Dr. Horvath-Puho has nothing to disclose. Dr. Gradus has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Lash has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Lash has received publishing royalties from a publication relating to health care. Maria Glymour has nothing to disclose. Prof. Soerensen has nothing to disclose. Dr. Henderson has stock in Abbott, Amgen, Roche. The institution of Dr. Henderson has received research support from NIH. The institution of Dr. Henderson has received research support from Health IQ. Dr. Henderson has received personal compensation in the range of $500-$4,999 for serving as a External advisory committee member, Alzheimer’s Disease Center with University of Kansas. Dr. Henderson has a non-compensated relationship as a adjunct (honorary) professor with Aarhus University that is relevant to AAN interests or activities.

A Novel Process to Recruit and Select Community Partners for a Hybrid Implementation-Effectiveness Study.

Creating strong partnerships with community organizations is essential to test implementation of evidence-based interventions. However, partners are often chosen based on convenience rather than capacity or diversity. Streamlined processes are needed to identify qualified, diverse, and invested partners to conduct community-based research. There is a gap in the literature on effective and efficient processes for recruiting partners. This paper aims to fill that gap by describing a novel approach for identifying a diverse group of community organizations to participate in research. We used a Request for Partners (RFP) approach to recruit partners to participate in a hybrid implementation-effectiveness study of the Veggie Van mobile market model. The process included formative work to inform RFP development, creation of an external advisory committee, an intent-to-apply round, a full application round, and an inperson training and selection process. Data was collected to characterize applicant size, location, and experience; pre-post surveys were conducted to understand the training's utility. We received 59 intent-to-apply submissions and invited 28 organizations to apply: 17 submitted applications and 12 organizations were chosen as finalists. The process took approximately 8 months to recruit 9 organizations and 32 community sites across 5 states and increased understanding of the intervention and partner responsibilities. An RFP process is familiar to many community organizations that compete for grant funding but may not have prior research experience. This process streamlined recruitment timelines, increased diversity, and cultivated community among organizations. It may also improve research transparency, study completion, and intervention fidelity.

Outcome reporting across randomized controlled trials evaluating potential treatments for male infertility: a systematic review.

STUDY QUESTIONWhat are the primary outcomes and outcome measures used in randomized controlled trials (RCTs) evaluating potential treatments for male infertility in the last 10 years?SUMMARY ANSWEROutcome reporting across male infertility trials is heterogeneous with numerous definitions and measures used to define similar outcomes.WHAT IS KNOWN ALREADYNo core outcome set for male infertility trials has been developed. Male infertility trials are unique in that they have potentially three participants, a man, a female partner and their offspring and this will likely lead to significant variation in outcome reporting in randomized trials.STUDY DESIGN, SIZE, DURATIONA systematic review of RCTs mapping outcomes and outcome measures evaluating potential treatments for men with infertility registered in the Cochrane Register of Controlled Trials (CENTRAL) between January 2010 and July 2021.PARTICIPANTS/MATERIALS, SETTING, METHODS screening and study selection was undertaken in duplicate using a review protocol that was developed prior to commencing the review. No risk of bias assessment was undertaken as this review aims to report on outcome reporting only.MAIN RESULTS AND THE ROLE OF CHANCEOne hundred and seventy-five RCTs were identified, and given the large number of studies we limited our review to the 100 largest trials. Seventy-nine different treatments were reported across the 100 largest RCTs including vitamin and dietary supplements (18 trials), surgical treatments (18 trials) and sperm selection techniques (22 trials). When considering the largest 100 trials (range: 80–2772 participants), 36 primary and 89 secondary outcomes were reported. Forty-seven trials reported a primary outcome and 36 trials clearly defined their primary outcome. Pregnancy outcomes were inconsistently reported and included pregnancy rate (51 trials), pregnancy loss including miscarriage, ectopic pregnancy, stillbirth (9 trials) and live birth (13 trials). Trials consistently reporting the same outcome frequently used different definitions. For example, semen quality was reported by 75 trials and was defined in 7 different ways, including; the World Health Organization (WHO) 2010 criteria (32 trials), WHO 1999 criteria (18 trials), WHO 1992 criteria (3 trials), WHO 1999 and 1992 criteria (1 trial) and the Kruger strict morphology criteria (1 trial).LIMITATIONS, REASONS FOR CAUTIONWe only evaluated the 100 largest trials published in the last 10 years and did not report outcomes on the remaining 75. An outcome was included as a primary outcome only if clearly stated in the manuscript and we did not contact authors to clarify this. As our review mapped outcomes and outcome measures, we did not undertake an integrity assessment of the trials included in our review.WIDER IMPLICATIONS OF THE FINDINGSMost randomized trials evaluating treatments for male infertility report different outcomes. Only half of the RCTs reported pregnancy rate and even fewer reported live birth; furthermore, the definitions of these outcomes varies across trials. Developing, disseminating and implementing a minimum data set, known as a core outcome set, for male infertility research could help to improve outcome selection, collection and reporting.STUDY FUNDING/COMPETING INTEREST(S)A.P.—chairman of external scientific advisory committee of Cryos International Denmark ApS, member of the scientific advisory board for Cytoswim LDT and ExSeed Health. Guest lecture at the ‘Insights for Fertility Conference’, funded by MERK SERONO Limited. M.v.W.—holds a ZON-MW research grant. No external funding was obtained for this study.

Applied Mindfulness for Physician Wellbeing: A Prospective Qualitative Study Protocol.

BackgroundPhysician burnout has significant adverse impacts on the wellbeing of individual physicians, and by extension the healthcare delivery systems of which they are part. Mindfulness is consistently cited as a pragmatic approach to effectively address burnout and enhance physician wellbeing. However, very few empirical studies have been published on Mindfulness Based Interventions (MBIs) for physicians. Moreover, the majority of these studies have been quantitative, leaving a gap in understanding the practical application of mindfulness in the context of physicians' daily lives.ObjectivesThis paper outlines the rationale, development and design of a novel prospective qualitative study examining the acceptability, feasibility, and pragmatic application of a mindfulness intervention for physician wellness.MethodsThe study will be conducted in three groups of at least 8 practicing physicians from a broad range of medical specialties at a tertiary care hospital in a large urban center in Eastern Canada. The intervention will consist of an innovative program based on the teachings of internationally renowned scholar and Zen Master Thích Nhãt Hạnh. It will include 5 weekly 2-h mindfulness sessions delivered by two health providers trained in mindfulness and in the teachings of Thich Nhat Hanh. The primary outcome measure will be an in-depth Thematic Analysis of post-program semi-structured interviews. Field data will also be collected through participant observation. The study will be theoretically grounded within the interpretive paradigm utilizing “the Mechanisms of Mindfulness Theory”. An external advisory committee formed by four senior members of Thích Nhãt Hạnh's community will provide guidance across all phases of the study.DiscussionOur innovative approach provides a new framework to further understand the mechanisms by which mindfulness interventions can impact physician wellbeing, and by extension their patients, colleagues, and broader healthcare systems. Through a clear articulation of the rigorous application of accepted procedures and standards used in our protocol, this paper seeks to provide a roadmap for other researchers who wish to develop further studies in this area. Lessons learned in the preparation and conduction of this study can be applied to other healthcare contexts including non-physician health provider wellbeing, clinical care, and population-level mental health.

Measure of Value: FDA in the Age of COVID

The US Food and Drug Administration (FDA) is the institutional regulatory gateway through which healthcare business sectors gain access to commercial markets in pharmaceuticals, biologicals, vaccines, medical devices, diagnostic test kits and persona protective equipment. The unfolding of events for the COVID-19 pandemic serve as a case study for understanding, in real time, how FDA has contributed value to the healthcare sector. Federal regulatory agencies, such as FDA, require strong processes to provide fair and consistent outcomes to retain the trust of the stakeholder community. These processes include statutes and regulations, internal manual of standard operating procedures and policies, guidance documents, external advisory committees and the Office of Inspector General. These processes cover the following activities: product development conditions, regulatory pathways, types of approvals, manufacturing quality, and post marketing safety. Together, the institutional experiences that led to and shaped these processes prepared FDA for the challenges associated with COVID-19. The sum of twelve decades of experience comes down to the following goals that provide value to the degree with which each is successful: 1) The manufacturing process must meet standards of quality and be secured. 2) Medical products must be shown, through scientific evidence and based on evidentiary standards, to be safe and effective for human use. 3) Identified risks must be mitigated, by labeling at a minimum, with additional strategies as necessary. 4) Provisions must exist for extraordinary circumstances of limited unmet medical needs and of threats to public health and national security. https://doi.org/10.21423/jrs-v10i1beninger

My head just exploded, now what? Aducanumab.

My head just exploded, now what? Aducanumab.

Piloting During a Pandemic

Key TakeawaysFour pilot teams shared experiences with piloting during the COVID‐19 pandemic, emphasizing that thoughtful planning streamlines the piloting process while mitigating the risk of transmitting illness.Remote access to and control of pilot equipment, along with the use of virtual communication platforms, enabled teams to successfully perform pilot‐scale studies.Operating pilot systems through the pandemic allowed teams to respond to drastic changes on a small scale to mitigate risks around full‐scale processes at the treatment plant.

A Roadmap to Patient Engagement: Facioscapulohumeral Muscular Dystrophy and the ReSolve Clinical Trial.

We describe our efforts to overcome barriers to patient engagement in facioscapulohumeral muscular dystrophy (FSHD) and offer a roadmap that can be replicated in other rare neurologic disorders. We implemented an engagement plan during Clinical Trial Readiness to Solve Barriers to Drug Development for FSHD (ReSolve), an 18-month, multisite, observational study of individuals with FSHD. Elements of our engagement plan included conducting focus groups during protocol development, patient involvement on the ReSolve external advisory committee, creation of a patient advisory committee, and collaboration with patient advocacy groups. Patient feedback led to adaptations in the study protocol and to changes in recruitment and retention methods. Patient engagement ensures that the patient voice contributes to multiple aspects of trial design and implementation. Our engagement efforts exemplify how collaboration with patients and families can be accomplished in FSHD and the resultant roadmap process may be replicable in other rare neurologic diseases.

Joseph V. Simone: In Memoriam (1935–2021)

![][1] He was a poet. A prodigious writer. A giant in the world of pediatric oncology. Those of us in the field of cancer research, as well as patients around the globe, owe a tremendous debt of gratitude to Joseph “Joe” Simone. A first-generation American who was born amid the

Governance and funding best practices for embedded research programs

Health systems are increasingly embracing embedded research (ER) program models that allow researchers to integrate into operational and clinical practices. Successful ER programs rely on unique funding streams and bidirectional relationships with health system operational and executive leaders. This commentary summarizes current practices and recommendations for funding and governing ER programs. Three funding best practices are recommended: a mixed portfolio of short-term and long-term projects funded through a combination of internal and external sources; leveraging the community benefit requirement of non-profit hospitals and forming connections in the development office; and a research and implementation franchise model. Governance best practices include a strong relationship between researchers, operational and executive leaders and an external advisory committee to ensure that research topics are relevant to the needs of patients, the health system, and other stakeholders. These recommended best practices can help lay the foundation for early attempts to identify shared challenges and successes as health systems establish new ER programs and existing programs continue to mature.

Strategic Options for More Effective Indigenous Participation in Collaborative Environmental Governance

This research focuses on how Indigenous peoples might participate in collaborative environmental governance initiated by networked nongovernmental organizations (NGOs). Fourteen Indigenous and six non-Indigenous board members and partners of Canadian Model Forests were interviewed and discussed seven aspects of collaborative governance affecting Indigenous participation: purpose and vision; decision-making structure(s); roles and responsibilities; engagement; capacity; leadership; and, cultural suitability. Participants described four possible participation structures: external advisory committee; internal board subcommittee; hybrid internal–external advisory board; and internal ad hoc group. Here, design options and implications of each model are considered, offering choices for engagement where NGOs seek to lead collaborative approaches.

Standardised patient encounters to improve quality of counselling for pre-exposure prophylaxis (PrEP) in adolescent girls and young women (AGYW) in Kenya: study protocol of a cluster randomised controlled trial

IntroductionAdolescent girls and young women (AGYW) in sub-Saharan Africa are at high risk of HIV acquisition. Pre-exposure prophylaxis (PrEP) demonstration projects observe that AGYW uptake and adherence to PrEP during...

Scientific integrity effort at EPA needs more work

The US Environmental Protection Agency needs to do more to champion its policy on scientific integrity, the EPA’s independent watchdog says. In a report based on a 2018 survey of agency staff members, the EPA Office of Inspector General finds more than half of the respondents dissatisfied with how the agency releases scientific information to the public. Respondents said that information was not released in a timely fashion and that EPA leaders interfered with or suppressed its release, possibly because of political or industry influence, according to the report. The survey also says most respondents were satisfied with peer review and advice from external advisory committees. Most were dissatisfied with the EPA’s management of those advisory panels, however, citing 2017 changes on who can serve on them—changes recently thrown out by a federal court. Hundreds of respondents indicated that they had experienced but didn’t report possible violations of the scientific

Development and pilot of a prescription drug monitoring program and communication intervention for pharmacists.

Pharmacists' role in addressing the opioid crisis continues to expand, but lack of training specifically related to standardized prescription drug monitoring program (PDMP) use and communication strategies for provider and patient interactions remains a significant issue. We developed the Resources Encouraging Safe Prescription Opioid and Naloxone Dispensing (RESPOND) Toolkit to enhance community pharmacists' understanding of their role in addressing opioid safety; improve integration of PDMP into daily workflow; and enhance communication between pharmacists, prescribers, and patients. To describe the development of RESPOND Toolkit and summarize findings from initial pilot testing. RESPOND development was informed by focus groups with patients, prescribers, and pharmacists and an external advisory committee. Materials developed include a patient screening & communication algorithm, a provider communication checklist and an online continuing education course with three distinct modules. The RESPOND Toolkit was pilot tested in six community pharmacies in Oregon across two 6-month intervention phases. Pilot data collection included a pre-post intervention survey, pre-post knowledge assessment quizzes within the online course, and post-intervention semi-structured interviews. Interview feedback informed revisions after each phase to shape the final content, flow, and delivery of RESPOND. Sixteen of 21 pharmacists completed the online training, revealing a large, significant effect on knowledge gain across the three training modules (pre-score 57, post-score 84; p<0.001; Cohen's d=1.85). Of these participants, 10 also completed the baseline and post intervention survey and showed non-significant moderate improvements in knowledge, perceived behavioral control, and self-efficacy to address opioid safety issues. The RESPOND Toolkit has promise as an effective and scalable approach to providing community pharmacist-tailored training, especially in the areas of effective communication and workflow integration, to promote behavioral shifts supporting opioid safety for patients. Further development and testing in a larger sample is warranted.

Prioritization of rehabilitation Domains for establishing spinal cord injury high performance indicators using a modification of the Hanlon method: SCI-High Project

Objectives: To prioritize Domains of SCI Rehabilitation Care (SCI-Care) based on clinical importance and feasibility to inform the development of indicators of quality SCI-Care for adults with SCI/D in Canada.Methods: A 17-member external advisory committee, comprised of key stakeholders, ranked 15/37 Domains of rehabilitation previously flagged by the E-scan project team for gaps between knowledge generation and clinical implementation. Priority scores (D) were calculated using the Hanlon formula: , where A is prevalence, B is seriousness, and C is the effectiveness of available interventions. A modified “EAARS” (Economic, Acceptability, Accessibility, Resources, and Simplicity) criterion was used to rank feasibility on a scale of 0–4 (4 is high). The product of these two scores determined the initial Domain ranking. Following the consensus process, further changes were made to the Domain rankings.Results: Despite a low feasibility score, Sexual Health was ranked as high priority; and, the Community Participation and Employment Domains were merged. The 11 final prioritized Domains in alphabetic order were: Cardiometabolic Health; Community Participation and Employment; Emotional Well-Being; Reaching, Grasping, and Manipulation; Self-Management; Sexual Health; Tissue Integrity; Urinary Tract Infection; Urohealth; Walking, and Wheeled Mobility.Conclusions: The modified Hanlon method was used to facilitate prioritization of 11 of 37 Domains to advance the quality of SCI-care by 2020. In future, the Spinal Cord Injury Rehabilitation Care High Performance Indicators (SCI-High) Project Team will develop structure, process and outcome indicators for each prioritized Domain.

How a Public Health Goal Became a National Law: The Healthy, Hunger-Free Kids Act of 2010.

This case study provides insights into policy strategy and advocacy best practices that resulted in passage of the Healthy, Hunger-Free Kids Act of 2010, a public health law that resulted in improvements to school foods and beverages across the country. Congress reauthorizes child nutrition programs such as the National School Lunch Program and School Breakfast Program every 5 years. The Healthy, Hunger-Free Kids Act of 2010 is the legislation that reauthorized the child nutrition programs through September 30, 2015, and continues in effect today. We conducted stakeholder interviews and reviewed the legislative and regulatory history of the Healthy, Hunger-Free Kids Act of 2010 and advocates’ files. We formed an external advisory committee which helped to develop the interview questions and list of interviewees and reviewed the content of the case study. This case study focuses on the provisions that address the nutritional quality of school meals, snacks, and beverages and covers the period from 2004 to 2016. Overall, the case study demonstrates a number of key lessons to help inform other nutrition and public health policy initiatives, as well as continued implementation and defense of school nutrition. For instance, how advocates used research to develop and advocate for policy change, compromises that were needed to advance the policies, changes in attitudes about school food policy over time, framing and messaging, the role of state and local policy that contributed to national change, and how challenges were resolved between stakeholders.

A Model of Care for Osteoarthritis of the Hip and Knee: Development of a System-Wide Plan for the Health Sector in Victoria, Australia.

Osteoarthritis (OA) imposes a significant burden to the person, the health system and the community. Models of Care (MoCs) drive translation of evidence into policy and practice and provide a platform for health system reform. The Victorian MoC for OA of the hip and knee was developed following a best-practice framework, informed by best-evidence and iterative cross-sector consultation, including direct consumer consultation. Governance and external expert advisory committees consisting of local OA care champions facilitated the development and consultation processes. The MoC outlines key components of care, care that is not recommended, and suggests phased implementation strategies. This paper describes the MoC development process and lessons learned.