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. 2019 May 9;14(1):102.
doi: 10.1186/s13023-019-1069-6.

Priorities when deciding on participation in early-phase gene therapy trials for Duchenne muscular dystrophy: a best-worst scaling experiment in caregivers and adult patients

Ryan S Paquin  1 , Ryan Fischer  2 , Carol Mansfield  3 , Brennan Mange  3 , Katherine Beaverson  4 , Annie Ganot  5 , Amy Strong Martin  6 , Carl Morris  5 , Colin Rensch  2 , Valeria Ricotti  5 , Leo J Russo  4 , Alesia Sadosky  4 , Edward C Smith  7 , Holly L Peay  8
Affiliations

Priorities when deciding on participation in early-phase gene therapy trials for Duchenne muscular dystrophy: a best-worst scaling experiment in caregivers and adult patients

Ryan S Paquin et al. Orphanet J Rare Dis. .

Abstract

Purpose: Several gene therapy trials for Duchenne muscular dystrophy initiated in 2018. Trial decision making is complicated by non-curative, time-limited benefits; the progressive, fatal course; and high unmet needs. Here, caregivers and patients prioritize factors influencing decision making regarding participation in early-phase gene therapy trials.

Methods: We conducted a best-worst scaling experiment among U.S. caregivers and adults with Duchenne (N = 274). Participants completed 11 choice sets, choosing features they cared about most and least when deciding whether to participate in a hypothetical gene therapy trial. We analyzed the data using sequential conditional logistic regression.

Results: Participants prioritized improved muscle function in trial decision making. Concerns about participation limiting later use of gene transfer and editing were also important, as were improved lung and heart function. Low risk of death fell near the middle. Participants cared least about muscle biopsies and potential for randomization to placebo. Adults with Duchenne and caregivers of non-ambulatory children significantly prioritized improved lung function compared to caregivers of ambulatory children.

Conclusion: Our data demonstrate prioritization of anticipated benefits and opportunity costs relative to potential harms and procedures in gene therapy trial decision making. Such data inform protocol development, education and advocacy efforts, and informed consent.

Keywords: Best-worst scaling; Duchenne muscular dystrophy; Gene therapy; Stated preference.

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Conflict of interest statement

Authors’ information

Not applicable.

Ethics approval and consent to participate

The study protocol received IRB review and approval from RTI International’s Committee for the Protection of Human Subjects.

Consent for publication

Not Applicable.

Competing interests

RP– Declares no conflict of interest.

RF– Full-time employee of Parent Project Muscular Dystrophy, which receives funding from Solid Bioscience and Pfizer in support of preference research programs.

CM (1)– Declares no conflict of interest.

BM – Declares no conflict of interest.

KB – Full-time employee of Pfizer Inc. with stock holdings related to employment.

AG – Employee and co-founder of Sold Biosciences, with stock holdings related to employment.

AM – Declares no conflict of interest.

CM (2)– Employee of Solid Biosciences and former employee of Pfizer, with stock holdings related to employment.

CR – Declares no conflict of interest.

VR – Employee of Solid Biosciences with stock holdings related to employment.

LR – Full-time employee of Pfizer Inc. with stock holdings related to employment.

AS – Full-time employee of Pfizer Inc. with stock holdings related to employment.

ECS – Receives salary support from Pfizer Inc. for role as PI on a gene therapy trial.

HP – Declares no conflict of interest.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Example best-worst scaling choice task
Fig. 2
Fig. 2
Plot showing relative importance hierarchy for participating in a gene therapy clinical trial. Estimates are odds ratios from the final conditional logit model. The black bars are estimates for which no interaction by participant subgroup was found and represent the average relative importance across all participants. The grey and white bars are importance estimates for “chance of improved lung function” among participants in each subgroup. Error bars represent the 95% confidence intervals for odds ratios. Muscle benefit is the reference category, constrained to equal 1
See this image and copyright information in PMC

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