Dataset Information

Establishing Patient-Centered Outcomes for MCT8 Deficiency: Stakeholder Engagement and Systematic Literature Review.

ABSTRACT:

Introduction

The SCL16A2 gene encodes the thyroid hormone (TH) transporter MCT8. Pathogenic variants result in a reduced TH uptake into the CNS despite high serum T3 concentrations. Patients suffer from severe neurodevelopmental delay and require multidisciplinary care. Since a first compassionate use study in 2008, the development of therapies has recently gained momentum. Treatment strategies range from symptom-based approaches, supplementation with TH or TH-analogs, to gene therapy. All these studies have mainly used surrogate endpoints and clinical outcomes. However, the EMA and FDA strongly encourage researchers to involve patients and their advocacy groups in the design of clinical trials. This should strengthen the patients' perspective and identify clinical endpoints that are clinically relevant to their daily life.

Methods

We involved patient families to define patient-relevant outcomes for MCT8 deficiency. In close collaboration with patient families, we designed a questionnaire asking for their five most preferred therapeutic goals, which, if achieved at least, make a difference in their lives. In addition, we performed a systematic review according to Cochrane recommendations of the published treatment trials.

Results

We obtained results from 15 families with completed questionnaires from 14 mothers and 8 fathers. Improvement in development, especially in gross motor skills, was most important to the parents. 59% wished for head control and 50% for sitting ability. Another 36% wished for weight gain, 32% for improvement of expressive language skills, and 18% for a reduction of dystonia/spasticity, less dysphagia, and reflux. Paraclinical aspects were least important (5-9%). In a treatment trial (n=46) and compassionate use cases (n=83), the results were mainly inconclusive, partly due to a lack of predefined patient-centered clinical endpoints.

Discussion

We recommend that future trials should define a relevant improvement in "development" and/or other patient-relevant outcomes compared to natural history as treatment goals.

SUBMITTER: Wilpert NM

PROVIDER: S-EPMC10595182 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Establishing Patient-Centered Outcomes for MCT8 Deficiency: Stakeholder Engagement and Systematic Literature Review.

Wilpert Nina-Maria NM Tonduti Davide D Vaia Ylenia Y Krude Heiko H Sarret Catherine C Schuelke Markus M

Neuropsychiatric disease and treatment 20231020

<h4>Introduction</h4>The <i>SCL16A2</i> gene encodes the thyroid hormone (TH) transporter MCT8. Pathogenic variants result in a reduced TH uptake into the CNS despite high serum T3 concentrations. Patients suffer from severe neurodevelopmental delay and require multidisciplinary care. Since a first compassionate use study in 2008, the development of therapies has recently gained momentum. Treatment strategies range from symptom-based approaches, supplementation with TH or TH-analogs, to gene the ...[more]

PMID: 37881807

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Project description:Introduction/objectivesThe engagement of patients and other stakeholders is a critical element in the design of patient-centered outcomes research studies. However, methodology for scalable engagement in research management particularly activities such as operationalization of principles and setting of priorities is not well-developed. The objective of this study is to describe a novel approach for scalable stakeholder engagement in research aligned with the Patient-Centered Outcomes Research Institute (PCORI) engagement principles, which was evaluated in a national clinical data research network.Materials and methodsPatient, patient advocate, clinician, and researcher stakeholders were recruited from clinical sites, as well as social media sites related to the 3 conditions of focus, heart failure, obesity, and Kawasaki disease. The engagement strategy was designed, implemented, and mapped to the PCORI engagement principles. Evaluation included internal assessment and quantitative measures of online engagement.ResultsWe operationalized the PCORI principles with 12 stakeholder engagement strategies and convened stakeholder advisory boards and online research prioritization panels to determine research priorities in a rigorous, deliberative process. A total of 46 advisors (20 patients) and 339 panelists (159 patients) actively participated. There were not significant differences between patients and clinicians in level of online engagement. Nonetheless, while patients reported a slightly greater challenge with following online discussion, they overall had a more favorable opinion about use of the online format.Discussion/conclusionAn efficient way to engage large numbers of representative stakeholders in research is a necessary first step to assure the public of trustworthy use of data networks for health research. This paper describes a comprehensive approach to engagement in patient-centered outcomes research management that informs ongoing development of rigorous methodologies in this area.

Project description:BackgroundInvolving patient and community stakeholders in clinical trials adds value by ensuring research prioritizes patient goals both in conduct of the study and application of the research. The use of stakeholder committees and their impact on the conduct of a multicenter clinical trial have been underreported clinically and academically. The aim of this study is to describe how Study Advisory Committee (SAC) recommendations were implemented throughout the Emergency Medicine Palliative Care Access (EMPallA) trial. EMPallA is a multi-center, pragmatic two-arm randomized controlled trial (RCT) comparing the effectiveness of nurse-led telephonic case management and specialty, outpatient palliative care of older adults with advanced illness.MethodsA SAC consisting of 18 individuals, including patients with palliative care experience, members of healthcare organizations, and payers was convened for the EMPallA trial. The SAC engaged in community-based participatory research and assisted in all aspects from study design to dissemination. The SAC met with the research team quarterly and annually from project inception to dissemination. Using meeting notes and recordings we completed a qualitative thematic analysis using an iterative process to develop themes and subthemes to summarize SAC recommendations throughout the project's duration.ResultsThe SAC convened 16 times between 2017 and 2020. Over the course of the project, the SAC provided 41 unique recommendations. Twenty-six of the 41 (63%) recommendations were adapted into formal Institutional Review Board (IRB) study modifications. Recommendations were coded into four major themes: Scientific, Pragmatic, Resource and Dissemination. A majority of the recommendations were related to either the Scientific (46%) or Pragmatic (29%) themes. Recommendations were not mutually exclusive across three study phases: Preparatory, execution and translational. A vast majority (94%) of the recommendations made were related to the execution phase. Major IRB study modifications were made based on their recommendations including data collection of novel dependent variables and expanding recruitment to Spanish-speaking patients.ConclusionsOur study provides an example of successful integration of a SAC in the conduct of a pragmatic, multi-center RCT. Future trials should engage with SACs in all study phases to ensure trials are relevant, inclusive, patient-focused, and attentive to gaps between health care and patient and family needs.Trial registrationClinicaltrials.gov Identifier: NCT03325985, 10/30/2017.

Project description:BACKGROUND: A compelling ethical rationale supports patient engagement in healthcare research. It is also assumed that patient engagement will lead to research findings that are more pertinent to patients' concerns and dilemmas. However; it is unclear how to best conduct this process. In this systematic review we aimed to answer 4 key questions: what are the best ways to identify patient representatives? How to engage them in designing and conducting research? What are the observed benefits of patient engagement? What are the harms and barriers of patient engagement? METHODS: We searched MEDLINE, EMBASE, PsycInfo, Cochrane, EBSCO, CINAHL, SCOPUS, Web of Science, Business Search Premier, Academic Search Premier and Google Scholar. Included studies were published in English, of any size or design that described engaging patients or their surrogates in research design. We conducted an environmental scan of the grey literature and consulted with experts and patients. Data were analyzed using a non-quantitative, meta-narrative approach. RESULTS: We included 142 studies that described a spectrum of engagement. In general, engagement was feasible in most settings and most commonly done in the beginning of research (agenda setting and protocol development) and less commonly during the execution and translation of research. We found no comparative analytic studies to recommend a particular method. Patient engagement increased study enrollment rates and aided researchers in securing funding, designing study protocols and choosing relevant outcomes. The most commonly cited challenges were related to logistics (extra time and funding needed for engagement) and to an overarching worry of a tokenistic engagement. CONCLUSIONS: Patient engagement in healthcare research is likely feasible in many settings. However, this engagement comes at a cost and can become tokenistic. Research dedicated to identifying the best methods to achieve engagement is lacking and clearly needed.

Dataset Information

Establishing Patient-Centered Outcomes for MCT8 Deficiency: Stakeholder Engagement and Systematic Literature Review.

Introduction

Methods

Results

Discussion

Publications

Establishing Patient-Centered Outcomes for MCT8 Deficiency: Stakeholder Engagement and Systematic Literature Review.

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