HARmonized Protocol Template to Enhance Reproducibility of Hypothesis Evaluating Real-World Evidence Studies on Treatment Effects: A Good Practices Report of a Joint ISPE/ISPOR Task Force

Shirley V Wang; Anton Pottegård; William Crown; Peter Arlett; Darren M Ashcroft; Eric I Benchimol; Marc L Berger; Gracy Crane; Wim Goettsch; Wei Hua; Shaum Kabadi; David M Kern; Xavier Kurz; Sinead Langan; Takahiro Nonaka; Lucinda Orsini; Susana Perez-Gutthann; Simone Pinheiro; Nicole Pratt; Sebastian Schneeweiss; Massoud Toussi; Rebecca J Williams

doi:10.1016/j.jval.2022.09.001

HARmonized Protocol Template to Enhance Reproducibility of Hypothesis Evaluating Real-World Evidence Studies on Treatment Effects: A Good Practices Report of a Joint ISPE/ISPOR Task Force

Value Health. 2022 Oct;25(10):1663-1672. doi: 10.1016/j.jval.2022.09.001.

Authors

Shirley V Wang¹, Anton Pottegård², William Crown³, Peter Arlett⁴, Darren M Ashcroft⁵, Eric I Benchimol⁶, Marc L Berger⁷, Gracy Crane⁸, Wim Goettsch⁹, Wei Hua¹⁰, Shaum Kabadi¹¹, David M Kern¹², Xavier Kurz⁴, Sinead Langan¹³, Takahiro Nonaka¹⁴, Lucinda Orsini¹⁵, Susana Perez-Gutthann¹⁶, Simone Pinheiro¹⁰, Nicole Pratt¹⁷, Sebastian Schneeweiss¹⁸, Massoud Toussi¹⁹, Rebecca J Williams²⁰

Affiliations

¹ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: swang1@bwh.harvard.edu.
² University of Southern Denmark, Odense, Denmark.
³ Brandeis University, Waltham, Massachusetts, USA.
⁴ European Medicines Agency, London, UK.
⁵ School of Health Sciences, University of Manchester, Manchester, UK.
⁶ Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada; Department of Paediatrics and Institute of Health Policy, Management and Evaluation, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
⁷ Independent Consultant, New York, USA.
⁸ Roche Pharmaceuticals, Camberley, UK.
⁹ The National Health Care Institute, Diemen, The Netherlands; Utrecht University, Utrecht, The Netherlands.
¹⁰ US Food and Drug Administration, Silver Springs, Maryland, USA.
¹¹ Sanofi-Aventis US LLC, North Potomac, Maryland, USA.
¹² Janssen Research & Development, LLC, Philadelphia, Pennsylvania, USA.
¹³ London School of Tropical Hygiene, London, UK.
¹⁴ Pharmaceutical and Medical Devices Agency, Japan.
¹⁵ COMPASS Pathways Ltd, Skillman, UK.
¹⁶ RTI Health Solutions, Barcelona, Spain.
¹⁷ Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, South Australia, Australia.
¹⁸ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁹ IQVIA, France.
²⁰ Bethesda, Maryland, USA.

PMID: 36241338
DOI: 10.1016/j.jval.2022.09.001

Abstract

Objectives: Ambiguity in communication of key study parameters limits the utility of real-world evidence (RWE) studies in healthcare decision-making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias.

Methods: The International Society for Pharmacoepidemiology (ISPE) and ISPOR-The Professional Society for Health Economics and Outcomes Research (ISPOR) convened a joint task force, including representation from key international stakeholders, to create a harmonized protocol template for RWE studies that evaluate a treatment effect and are intended to inform decision-making. The template builds on existing efforts to improve transparency and incorporates recent insights regarding the level of detail needed to enable RWE study reproducibility. The over-arching principle was to reach for sufficient clarity regarding data, design, analysis, and implementation to achieve 3 main goals. One, to help investigators thoroughly consider, then document their choices and rationale for key study parameters that define the causal question (e.g., target estimand), two, to facilitate decision-making by enabling reviewers to readily assess potential for biases related to these choices, and three, to facilitate reproducibility.

Strategies to disseminate and facilitate use: Recognizing that the impact of this harmonized template relies on uptake, we have outlined a plan to introduce and pilot the template with key international stakeholders over the next 2 years.

Conclusion: The HARmonized Protocol Template to Enhance Reproducibility (HARPER) helps to create a shared understanding of intended scientific decisions through a common text, tabular and visual structure. The template provides a set of core recommendations for clear and reproducible RWE study protocols and is intended to be used as a backbone throughout the research process from developing a valid study protocol, to registration, through implementation and reporting on those implementation decisions.

Keywords: protocol; real world evidence; reproducibility; transparency.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Advisory Committees*
Humans
Outcome Assessment, Health Care / methods
Pharmacoepidemiology
Reproducibility of Results
Research Report*

Abstract

Publication types

MeSH terms

Grants and funding