Patient-reported outcomes validated in phase 3 clinical trials: a targeted literature review

Abstract

Background

Regulatory guidance advises validation of patient-reported outcome (PRO) instruments prior to use in pivotal clinical studies, which may then be used to generate critical patient-centered evidence and support labelling claims. This targeted literature review aimed to determine if PRO instruments psychometrically validated in a phase 3 trial setting could support label claims from the same phase 3 study (i.e. PRO data were generated as an endpoint).

Methods

A targeted search of published studies (1 January 2006−3 June 2021) using the MEDLINE database identified PRO instruments validated during phase 3 trials. The search included instrument terms (e.g. patient-reported outcome measures, questionnaire, survey) and validation terms (e.g. reproducibility, minimal important difference), without filtering for therapeutic indications. Results were limited to phase 3 clinical trials or validation studies. The PROLABELS database was used to identify PROs validated in phase 3 trials and accepted in labelling claims.

Results

Of 355 references identified, 68 studies with PRO psychometric validation in phase 3 studies were selected, covering 78 instruments. Of these, 20 were novel PRO instruments and 58 were existing instruments being validated for a new therapeutic indication/population. The psychometric properties most frequently validated were internal consistency reliability, known-group validity, responsiveness, minimal important difference, and concurrent validity. Five novel instruments obtained ten labelling claims for seven drugs/products.

Conclusions

These results suggest that quantitative validation of novel PRO instruments, and existing PROs for new indications, can occur within the context of phase 3 trials, and these PROs can also support label claims.

Keywords:

• Targeted literature review
• patient-reported outcome
• phase 3 trial
• validated

Transparency

 

Declaration of funding

This study was sponsored by Astellas Pharma Global Development Inc. Medical writing support was funded by Astellas Pharma Inc.

Declaration of financial/other relationships

AM is an employee of, and holds stocks in, Astellas Pharma Europe; SD and RA are employees of Mapi, vendors contracted by Astellas Pharma Inc; JS is an employee of, and holds stocks in, Astellas Pharma Inc.

A reviewer on this manuscript disclosed that they are a full-time employee and shareholder of WCG Inc. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

All authors contributed to the study conception and design. SD and RA contributed to data collection and all authors contributed to the analysis and data interpretation. All authors commented on previous versions of the manuscript, and read and approved the final manuscript.

Acknowledgements

This study was initiated and supported by Astellas Pharma Global Development Inc. Medical writing support was provided by Tina Bristo, and Lisa O’Rourke, PhD, on behalf of Lumanity, funded by Astellas Pharma Inc. Lumanity assisted in drafting the manuscript under the direction of the authors and provided editorial support throughout its development. Medical writing support was funded by Astellas Pharma Inc. Data from this study was presented in part as a poster titled, “Patient-Reported Outcomes Validated in phase 3 Clinical Trials: A Targeted Literature Review” at the ISPOR 2022 congress on May 15–18, 2022.

Data availability statement

Researchers may request access to anonymized participant-level data, trial-level data and protocols from Astellas-sponsored clinical trials at www.clinicalstudydatarequest.com. For the Astellas criteria on data sharing, see: https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Astellas.aspx