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 Wang¹, Anton Pottegård², William Crown³, Peter Arlett⁴, Darren M Ashcroft⁵, Eric I Benchimol^{6

7

8}, Marc L Berger⁹, Gracy Crane¹⁰, Wim Goettsch^{11

12}, Wei Hua¹³, Shaum Kabadi¹⁴, David M Kern¹⁵, Xavier Kurz⁴, Sinead Langan¹⁶, Takahiro Nonaka¹⁷, Lucinda Orsini¹⁸, Susana Perez-Gutthann¹⁹, Simone Pinheiro¹³, Nicole Pratt²⁰, Sebastian Schneeweiss¹, Massoud Toussi²¹, Rebecca J Williams²²

Affiliations

¹ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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.
⁷ ICES, Toronto, Ontario, Canada.
⁸ Department of Paediatrics and Institute of Health Policy, Management and Evaluation, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
⁹ Independent Consultant, New York, USA.
¹⁰ Roche Pharmaceuticals, Camberley, UK.
¹¹ The National Health Care Institute, Diemen, The Netherlands.
¹² Utrecht University, Utrecht, The Netherlands.
¹³ US Food and Drug Administration, Silver Springs, Maryland, USA.
¹⁴ Sanofi-Aventis US LLC, North Potomac, Maryland, USA.
¹⁵ Janssen Research & Development, LLC, Philadelphia, Pennsylvania, USA.
¹⁶ London School of Tropical Hygiene, London, UK.
¹⁷ Pharmaceutical and Medical Devices Agency, Japan.
¹⁸ COMPASS Pathways Ltd, Skillman, UK.
¹⁹ RTI Health Solutions, Barcelona, Spain.
²⁰ Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, South Australia, Australia.
²¹ IQVIA, France.
²² Bethesda, Maryland, USA.

PMID: 36215113
PMCID: PMC9771861
DOI: 10.1002/pds.5507

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 et al. Pharmacoepidemiol Drug Saf. 2023 Jan.

. 2023 Jan;32(1):44-55.

doi: 10.1002/pds.5507. Epub 2022 Oct 10.

Authors

Affiliations

¹ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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.
⁷ ICES, Toronto, Ontario, Canada.
⁸ Department of Paediatrics and Institute of Health Policy, Management and Evaluation, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
⁹ Independent Consultant, New York, USA.
¹⁰ Roche Pharmaceuticals, Camberley, UK.
¹¹ The National Health Care Institute, Diemen, The Netherlands.
¹² Utrecht University, Utrecht, The Netherlands.
¹³ US Food and Drug Administration, Silver Springs, Maryland, USA.
¹⁴ Sanofi-Aventis US LLC, North Potomac, Maryland, USA.
¹⁵ Janssen Research & Development, LLC, Philadelphia, Pennsylvania, USA.
¹⁶ London School of Tropical Hygiene, London, UK.
¹⁷ Pharmaceutical and Medical Devices Agency, Japan.
¹⁸ COMPASS Pathways Ltd, Skillman, UK.
¹⁹ RTI Health Solutions, Barcelona, Spain.
²⁰ Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, South Australia, Australia.
²¹ IQVIA, France.
²² Bethesda, Maryland, USA.

PMID: 36215113
PMCID: PMC9771861
DOI: 10.1002/pds.5507

Abstract

Problem: 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.

What we did: 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 overarching 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.

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Conflict of interest statement

Drs. Wang, Pottegård, Crown, Arlett, Ashcroft, Berger, Goettsch, Hua, Kurz, Orsini, Pratt, have no conflicts of interest to declare. Dr. Schneeweiss is principal investigator of the FDA Sentinel Innovation Center funded by the FDA, co‐principal investigator of an investigator‐initiated grant to the Brigham and Women's Hospital from Boehringer Ingelheim unrelated to the topic of this study. He is a consultant to Aetion Inc., a software manufacturer of which he owns equity. His interests were declared, reviewed, and approved by the Brigham and Women's Hospital and Partners HealthCare System in accordance with their institutional compliance policies. Dr. Benchimol has acted as a legal consultant for Hoffman La‐Roche Limited and Peabody & Arnold LLP and acted as a consultant to McKesson Canada for matters unrelated to this manuscript. Dr. G Crane is an employee of F. Hoffmann‐La Roche Ltd and holds stocks in F. Hoffmann‐La Roche Ltd. Dr. Kabadi is an employee and shareholder of Sanofi. Dr. Kern is an employee of Janssen R&D, and stockholder of Johnson & Johnson. Dr. Perez‐Gutthann is an employee of RTI Health Solutions, a division of the independent nonprofit Research Triangle Institute, who conducts research under contract for pharmaceutical companies, private, public organizations. Dr. Pinheiro worked on this research and article while employed by the US FDA, but is now employed by Abbvie. Dr Toussi works for IQVIA, a Human data science company who receives funds from pharmaceutical industry, governments and non‐profit organizations to conduct research. Dr. Williams worked on this research and article while employed with the National Library of Medicine, NIH, but is no longer employed with NIH. The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency, the Food and Drug Administration, the Pharmaceutical and Medical Devices Agency or the National Institutes of Health.

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References

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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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources