Dataset Information

An International Multi-Stakeholder Delphi Survey Study on the Design of Disease Modifying Parkinson's Disease Trials.

ABSTRACT:

Background

Design of disease modification (DM) trials for Parkinson's disease (PD) is challenging. Successful delivery requires a shared understanding of priorities and practicalities.

Objective

To seek stakeholder consensus on phase 3 trials' overall goals and structure, inclusion criteria, outcome measures, and trial delivery and understand where perspectives differ.

Methods

An international expert panel comprising people with Parkinson's (PwP), care partners (CP), clinical scientists, representatives from industry, funders and regulators participated in a survey-based Delphi study. Survey items were informed by a scoping review of DM trials and PwP input. Respondents scored item agreement over 3 rounds. Scores and reasoning were summarized by participant group each round until consensus, defined as≥70% of at least 3 participant groups falling within the same 3-point region of a 9-point Likert scale.

Results

92/121 individuals from 13 countries (46/69 PwP, 13/18 CP, 20/20 clinical scientists, representatives from 8/8 companies, 4/5 funders, and 1/1 regulator) completed the study. Consensus was reached on 14/31 survey items: 5/8 overall goals and structure, 1/8 Eligibility criteria, 7/13 outcome measures, and 1/2 trial delivery items. Extent of stakeholder endorsement for 428 reasons for scores was collated across items.

Conclusions

This is the first systematic multi-stakeholder consultation generating a unique repository of perspectives on pivotal aspects of DM trial design including those of PwP and CP. The panel endorsed outcomes that holistically measure PD and the importance of inclusive trials with hybrid delivery models. Areas of disagreement will inform mitigating strategies of researchers to ensure successful delivery of future trials.

SUBMITTER: Zeissler ML

PROVIDER: S-EPMC10741330 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

An International Multi-Stakeholder Delphi Survey Study on the Design of Disease Modifying Parkinson's Disease Trials.

Zeissler Marie-Louise ML McFarthing Kevin K Raphael Karen G KG Rafaloff Gary G Windle Richard R Carroll Camille B CB

Journal of Parkinson's disease 20230101 8

<h4>Background</h4>Design of disease modification (DM) trials for Parkinson's disease (PD) is challenging. Successful delivery requires a shared understanding of priorities and practicalities.<h4>Objective</h4>To seek stakeholder consensus on phase 3 trials' overall goals and structure, inclusion criteria, outcome measures, and trial delivery and understand where perspectives differ.<h4>Methods</h4>An international expert panel comprising people with Parkinson's (PwP), care partners (CP), clinic ...[more]

PMID: 38007672

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Project description:BackgroundWith the dramatic increase in the pipeline for new sickle cell disease (SCD) therapies in recent years, the time is ripe to ensure a robust body of evidence is available for decision making by regulators, payers, clinicians, and patients. Harmonization of the outcomes selected across interventional trials enables optimal post-trial appraisal and decision making through valid pooled analyses and indirect comparisons. We employed a structured, multi-stakeholder consensus process to develop core outcome sets (COS) for use in clinical trials of SCD interventions.MethodsCoreSCD utilized a modified Delphi method adapted from the standards recommended by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. An initial list of candidate outcomes was developed through a targeted literature review and input from an 11-member advisory committee. A 44-member multi-stakeholder Delphi Panel was established and included patients and family members, advocates, clinicians, researchers, payers, health technology assessors, representatives from government agencies, and industry representatives. Patients/advocates comprised 25% of the Delphi Panel and orientation and training was provided prior to the consensus process to ensure all were prepared to participate meaningfully. Panelists completed three rounds of an online survey to rate the importance of candidate outcomes for inclusion in the COS. Summary data was provided between each voting round and an in-person consensus meeting was held between the second and third round of voting. Consensus rules were applied following each round of voting to eliminate outcomes that did not meet predetermined criteria for retention.ResultsConsensus was reached for two core outcome sets. The final COS for trials of disease-modifying therapies includes ten outcomes and the COS for trials of acute interventions includes six outcomes. Both core sets include clinical outcomes as well as outcomes related to functioning/quality of life, resource utilization, and survival/mortality.ConclusionsUse of the COS in clinical development programs for SCD will help to ensure that relevant, consistent outcomes are available for decision making across the product lifecycle.

Project description:Translation of disease-modifying therapies in neurodegenerative disease has been disappointing. Parkinson's disease (PD) was used to compare patterns of preclinical study design for symptomatic and potentially disease-modifying interventions. We examined the relationship of model, intervention type and timing, outcomes and outcome measures in 543 animal and human studies (1973-2015) across a contemporary cohort of animal and human interventional studies (n = 445), animal studies for approved interventions (n = 28), animal and human studies for those that failed to translate (n = 70). Detailed study design data were collected for 216 studies in non-human primate (NHP) and rodent toxin-induced models. Species-specific patterns of study design prevailed regardless of whether interventions were symptomatic or potentially disease-modifying. In humans and NHPs, interventions were typically given to both sexes well after the PD phenotype was established, and clinical outcome measures were collected at single (symptomatic) or multiple (disease-modifying) time-points. In rodents, interventions often preceded induction of the model, acute toxic protocols were common, usually given to young males, clinical outcome measures were used less commonly, and outcomes were less commonly assessed at multiple time points. These patterns were more prevalent in mice than rats. In contrast, study design factors such as randomization and blinding did not differ appreciably across symptomatic and disease-modifying intervention categories. The translational gap for potentially disease-modifying interventions in PD in part results from study designs, particularly in mice, that fail to model the progressive nature and relatively late intervention characteristic of PD, or that anchor mechanistic and neuropathologic data to longitudinal clinical outcomes. Even if measures to improve reproducibility are broadly adopted, perpetuation of these norms will continue to impede effective translation.

Dataset Information

An International Multi-Stakeholder Delphi Survey Study on the Design of Disease Modifying Parkinson's Disease Trials.

Background

Objective

Methods

Results

Conclusions

Publications

An International Multi-Stakeholder Delphi Survey Study on the Design of Disease Modifying Parkinson's Disease Trials.

Similar Datasets

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