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

Sep 2, 2026

This report presents a harmonized protocol template aimed at improving the reproducibility of hypothesis evaluation in real-world evidence studies focused on treatment effects. It consolidates good practices across multiple guideline and framework sources, describing the content expectations under protocol section headers. The document contrasts approaches combining free text guidance with structured tables, and maps template elements to standardized sections for consistency across study types such as cohort, nested case-control, pregnancy cohort, and self-controlled designs.

LanguageEnglish

CategoryGeneral

FormatPDF

Pages11

Reading Time4 min

AccessFree to download

High level summary

Protocol-whole report

PubMed search for protocol template

Template structure by section headers

| Title | 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 | Wang , Shirley V. ; Pottegård , Anton; Crown , William; Arlett , Peter; Ashcroft , Darren M. ; Benchimol , Eric I. ; Berger, Marc L. ; Crane , Gracy; Goettsch , Wim; Hua , Wei | | Published in | Value in Health | | Publication Date | 2022-10 | | Link | [http://hdl.handle. net/1874/424443](http://hdl.handle. net/1874/424443) | | Citation | Wang , S V, Pottegård , A , Crown , W, Arlett , P, Ashcroft , D M , Benchimol , EI , Berger, M L , Crane , G , Goettsch , W, Hua , W, Kabadi , S , Kern , D M , Kurz , X , Langan , S , Nonaka , T, Orsini , L , Perez-Gutthann , S , Pinheiro , S , Pratt , N , Schneeweiss , S , Toussi , M & Williams , R J 2022 , ' 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 in Health, vol. 25, no. 10, pp. 1663-1672. [https://](https://)[ ](https://)[doi.org/10.1016/j.jval.2022.09.001](doi.org/10.1016/j.jval.2022.09.001) | | Versions / License | Publisher version | | Rights | [https://www. uu. nl/en/university-library/license-and-reuse-conditions](https://www. uu. nl/en/university-library/license-and-reuse-conditions) | | EQUATOR search Sec􀀂on of report =“Protocol-whole report”
(N = 6) | | | --- | --- | | | | | 0 relevant | | | PubMed search
“Protocol template”
(N = 15) | | | --- | --- | | | | | 0 relevant | | | | | | | | | | --- | --- | --- | --- | --- | --- | | High level summary
Section Header | EMA GVP Mod VIII PASS (Rev 3, Oct 2017)
Largely free text, with guidance on what
to include under section headers details in the Guidance for the format and content of the
protocol of
non-interventional post-authorisation safety studies ([www.ema.europa.eu](www.ema.europa.eu)) | ISPE GPP (June 2015)
Largely free text, with
guidance on what to include under section
headers - details in report [https://www](https://www). pharmacoepi.
org/resources/ policies/ guidelines-08027/ | NESTcc (Feb 2020)
Largely free text, with guidance on what to include under section headers - details in NESTcc report | STaRT-RWE (Jan 2021)
Structured tables that lay
out operational
parameters tobe speciﬁed details in Wanget al, BMJ
Table 1 | HARPER
Harmonized Template
Combination of free text with structured tables under section headers
1, table | | Title page with administrative information (e.g.
title, registry ID,
drug/device ID, sponsor) | 1 | A, C, M | 2, 10 | Table of Contents | Table | | Table of contents | 2 | | | Table 9 | | | Abbreviations | 3 | | | Table 8 | | | Glossary of
terminology | | | | Table 1 | 1, table | | Responsible parties | 4 | B | | | 2, free text | | Abstract | 5 | D | | Table 2 | 3, table | | Amendments and updates | 6 | L | | | 4, table | | Milestones/timeline | 7 | E | | | 5, structured free text, table | | Rationale and background | 8 | G | 1 | Table 1 | 6, table | | Research question and objectives | 9 | F | 3 | Figure 1, Table 3 | 7.1, 7.2, free text,ﬁgure | | Study design | 9.1 | H1 | 7 | Table 3A, 3B, 3C, 3D, Table 6 | 7.3, free text, table | | Setting | 9.2 | H2 | 4 | Table 3B, 3E, 3F, 3G, 3H | 7.4, free text, table | | Variables | 9.3 | H4 | 5, 6 | | | | Device description | | | 2 | Table 3A, Appendices | 7.6, free text, table | | Data sources | 9.4 | H3 | | Table 7 | 7.9, free text, table | | Study size | 9.5 | H5 | 9 | Table 3A, Appendices | 7.7, free text, table | | Data management | 9.6 | H6, H7 | | Table 4, Table 5 | 7.5, free text, table | | Data analysis | 9.7 | H8 | 12 | | 7.8 free text, table | | Quality control | 9.8 | H9 | 11 | | | | Limitations of the methods | 9.9 | H10 | | | | | Other aspects | 9.1 | | |

FAQs

What is the purpose of the harmonized protocol template in this report?

To enhance reproducibility of hypothesis evaluation in real-world evidence studies examining treatment effects, by standardizing what to include under protocol section headers.

How does the report combine guideline guidance with structured elements?

It uses largely free-text guidance for sections in some frameworks, and in others provides structured tables that specify operational parameters alongside narrative sections.

What kinds of study designs and use cases does the template accommodate?

The template supports multiple real-world evidence designs, illustrated with use cases including cohort studies, nested case-control studies, pregnancy cohort studies, and self-controlled designs.

Sep 2, 2026

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