Review

. 2021 Jun 30;11(6):e045105.

doi: 10.1136/bmjopen-2020-045105.

SPIRIT-PRO Extension explanation and elaboration: guidelines for inclusion of patient-reported outcomes in protocols of clinical trials

Melanie Calvert^{1

2

3

4

5}, Madeleine King⁶, Rebecca Mercieca-Bebber⁷, Olalekan Aiyegbusi^{8

3}, Derek Kyte⁸, Anita Slade^{8

4}, An-Wen Chan⁹, E Basch¹⁰, Jill Bell¹¹, Antonia Bennett¹², Vishal Bhatnagar¹³, Jane Blazeby^{14

15}, Andrew Bottomley¹⁶, Julia Brown¹⁷, Michael Brundage¹⁸, Lisa Campbell¹⁹, Joseph C Cappelleri²⁰, Heather Draper²¹, Amylou C Dueck²², Carolyn Ells²³, Lori Frank²⁴, Robert M Golub²⁵, Ingolf Griebsch²⁶, Kirstie Haywood²⁷, Amanda Hunn²⁸, Bellinda King-Kallimanis¹³, Laura Martin²⁹, Sandra Mitchell³⁰, Thomas Morel³¹, Linda Nelson³², Josephine Norquist³³, Daniel O'Connor¹⁹, Michael Palmer³⁴, Donald Patrick³⁵, Gary Price⁸, Antoine Regnault³⁶, Ameeta Retzer⁸, Dennis Revicki³⁷, Jane Scott³⁸, Richard Stephens³⁹, Grace Turner^{8

4}, Antonia Valakas⁴⁰, Galina Velikova⁴¹, Maria von Hildebrand⁸, Anita Walker⁸, Lari Wenzel⁴²

Affiliations

¹ Centre for Patient Reported Outcome Research, Institute of Applied Health Research, University of Birmingham, Birmingham, UK M.Calvert@bham.ac.uk.
² Birmingham Health Partners Centre for Regulatory Science and Innovation, University of Birmingham, Birmingham, UK.
³ NIHR Biomedical Research Centre, Institute of Translational Medicine, Birmingham, UK.
⁴ NIHR Surgical Reconstruction and Microbiology Research Centre, Birmingham, UK.
⁵ NIHR Applied Research Collaboration West Midlands, University of Birmingham, Birmingham, UK.
⁶ Faculty of Science, School of Psychology, University of Sydney, Sydney, New South Wales, Australia.
⁷ Faculty of Medicine and Health, NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
⁸ Centre for Patient Reported Outcome Research, Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
⁹ Women's College Research Institute, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁰ University of North Carolina, Chapel Hill, North Carolina, USA.
¹¹ Oncology Digital Health, AstraZeneca, Gaithersburg, Maryland, USA.
¹² Cancer Outcomes Research Program, University of North Carolina, Chapel Hill, North Carolina, USA.
¹³ US Food and Drug Administration, Silver Spring, Maryland, USA.
¹⁴ NIHR Bristol Biomedical Research Centre, University of Bristol, Bristol, UK.
¹⁵ Division of Surgery, Head and Neck, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
¹⁶ Department of Quality of Life, European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
¹⁷ Clinical Trials Research Unit, University of Leeds, Leeds, UK.
¹⁸ Department of Oncology, Queen's University Cancer Research Institute, Kingston, Ontario, Canada.
¹⁹ Medicines and Healthcare Products Regulatory Agency, London, UK.
²⁰ Global Biometrics & Data Management-Statistics, Pfizer Inc, New York City, New York, USA.
²¹ University of Warwick, Coventry, UK.
²² Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona, USA.
²³ School of Population and Global Health, McGill University, Montreal, Quebec, Canada.
²⁴ Patient-Centered Outcomes Research Institute, Washington, DC, USA.
²⁵ JAMA, Chicago, Illinois, USA.
²⁶ Boehringer Ingelheim International GmbH, Ingelheim, Germany.
²⁷ Warwick Research in Nursing, University of Warwick, Warwick Medical School, Coventry, UK.
²⁸ Independent Advisor, Manchester, UK.
²⁹ Daiichi Sankyo Europe GmbH, Munchen, Germany.
³⁰ National Cancer Institute, Rockville, Maryland, USA.
³¹ Patient-Centered Outcomes Research, UCB Pharma, Brussels, Belgium.
³² Value Evidence and Outcomes-Patient Centered Outcomes, GSK, Collegeville, Pennsylvania, USA.
³³ Center for Observational Real-world Evidence (CORE), Patient-Centered Endpoints & Strategy, Merck & Co Inc, Kenilworth, New Jersey, USA.
³⁴ Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
³⁵ Department of Health Services, University of Washington, Seattle, Washington, USA.
³⁶ Modus Outcomes, Lyon, France.
³⁷ Outcomes Research Consulting, Sarasota, Florida, USA.
³⁸ Johnson and Johnson, Janssen Global Services LLC, High Wycombe, UK.
³⁹ National Cancer Research Institute Consumer Forum, London, UK.
⁴⁰ EMD Serono Inc, Healthcare Business of Merck KGaA, Darmstadt, Germany.
⁴¹ Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
⁴² University of California, Irvine, California, USA.

PMID: 34193486
PMCID: PMC8246371
DOI: 10.1136/bmjopen-2020-045105

Review

SPIRIT-PRO Extension explanation and elaboration: guidelines for inclusion of patient-reported outcomes in protocols of clinical trials

Melanie Calvert et al. BMJ Open. 2021.

. 2021 Jun 30;11(6):e045105.

doi: 10.1136/bmjopen-2020-045105.

Authors

Affiliations

¹ Centre for Patient Reported Outcome Research, Institute of Applied Health Research, University of Birmingham, Birmingham, UK M.Calvert@bham.ac.uk.
² Birmingham Health Partners Centre for Regulatory Science and Innovation, University of Birmingham, Birmingham, UK.
³ NIHR Biomedical Research Centre, Institute of Translational Medicine, Birmingham, UK.
⁴ NIHR Surgical Reconstruction and Microbiology Research Centre, Birmingham, UK.
⁵ NIHR Applied Research Collaboration West Midlands, University of Birmingham, Birmingham, UK.
⁶ Faculty of Science, School of Psychology, University of Sydney, Sydney, New South Wales, Australia.
⁷ Faculty of Medicine and Health, NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
⁸ Centre for Patient Reported Outcome Research, Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
⁹ Women's College Research Institute, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁰ University of North Carolina, Chapel Hill, North Carolina, USA.
¹¹ Oncology Digital Health, AstraZeneca, Gaithersburg, Maryland, USA.
¹² Cancer Outcomes Research Program, University of North Carolina, Chapel Hill, North Carolina, USA.
¹³ US Food and Drug Administration, Silver Spring, Maryland, USA.
¹⁴ NIHR Bristol Biomedical Research Centre, University of Bristol, Bristol, UK.
¹⁵ Division of Surgery, Head and Neck, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
¹⁶ Department of Quality of Life, European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
¹⁷ Clinical Trials Research Unit, University of Leeds, Leeds, UK.
¹⁸ Department of Oncology, Queen's University Cancer Research Institute, Kingston, Ontario, Canada.
¹⁹ Medicines and Healthcare Products Regulatory Agency, London, UK.
²⁰ Global Biometrics & Data Management-Statistics, Pfizer Inc, New York City, New York, USA.
²¹ University of Warwick, Coventry, UK.
²² Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona, USA.
²³ School of Population and Global Health, McGill University, Montreal, Quebec, Canada.
²⁴ Patient-Centered Outcomes Research Institute, Washington, DC, USA.
²⁵ JAMA, Chicago, Illinois, USA.
²⁶ Boehringer Ingelheim International GmbH, Ingelheim, Germany.
²⁷ Warwick Research in Nursing, University of Warwick, Warwick Medical School, Coventry, UK.
²⁸ Independent Advisor, Manchester, UK.
²⁹ Daiichi Sankyo Europe GmbH, Munchen, Germany.
³⁰ National Cancer Institute, Rockville, Maryland, USA.
³¹ Patient-Centered Outcomes Research, UCB Pharma, Brussels, Belgium.
³² Value Evidence and Outcomes-Patient Centered Outcomes, GSK, Collegeville, Pennsylvania, USA.
³³ Center for Observational Real-world Evidence (CORE), Patient-Centered Endpoints & Strategy, Merck & Co Inc, Kenilworth, New Jersey, USA.
³⁴ Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
³⁵ Department of Health Services, University of Washington, Seattle, Washington, USA.
³⁶ Modus Outcomes, Lyon, France.
³⁷ Outcomes Research Consulting, Sarasota, Florida, USA.
³⁸ Johnson and Johnson, Janssen Global Services LLC, High Wycombe, UK.
³⁹ National Cancer Research Institute Consumer Forum, London, UK.
⁴⁰ EMD Serono Inc, Healthcare Business of Merck KGaA, Darmstadt, Germany.
⁴¹ Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
⁴² University of California, Irvine, California, USA.

PMID: 34193486
PMCID: PMC8246371
DOI: 10.1136/bmjopen-2020-045105

Abstract

Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the impact of disease and treatment on patients' symptoms, function and quality of life. High-quality PRO data from trials can inform shared decision-making, regulatory and economic analyses and health policy. Recent evidence suggests the PRO content of past trial protocols was often incomplete or unclear, leading to research waste. To address this issue, international, consensus-based, PRO-specific guidelines were developed: the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension. The SPIRIT-PRO Extension is a 16-item checklist which aims to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection to minimise research waste, and ultimately better inform patient-centred care. This SPIRIT-PRO explanation and elaboration (E&E) paper provides information to promote understanding and facilitate uptake of the recommended checklist items, including a comprehensive protocol template. For each SPIRIT-PRO item, we provide a detailed description, one or more examples from existing trial protocols and supporting empirical evidence of the item's importance. We recommend this paper and protocol template be used alongside the SPIRIT 2013 and SPIRIT-PRO Extension paper to optimise the transparent development and review of trial protocols with PROs.

Keywords: clinical trials; education & training (see medical education & training); protocols & guidelines; statistics & research methods.

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Conflict of interest statement

Competing interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and declare: SPIRIT-PRO group members were reimbursed for travel/subsistence at the consensus meeting. MC is Director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, Director of the Centre for the Centre for Patient Reported Outcomes Research and is a National Institute for Health Research (NIHR) Senior Investigator. MC has received personal fees from Astellas, Takeda, Merck, Daiichi Sankyo, Glaukos, GSK and the Patient-Centred Outcomes Research Institute (PCORI) outside the submitted work. RM-B reports non-financial support from University of Birmingham. OA, DK and ARet report grants from NIHR. OA and DK report grants from Birmingham Biomedical Research Centre (BRC). OA reports grants from UCB Pharma and also receives funding from the Health Foundation and declares personal fees from Gilead Sciences Ltd. DK and ARet report grants from Innovate UK and Macmillan Cancer Support. DK reports grants from Kidney Research UK, NIHR SRMRC at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, personal fees from Merck, GSK. EB declares personal fees from Navigating Cancer, Sivan Healthcare, CareVive Systems and AstraZeneca. Bell reports other from AstraZeneca, is an employee with stock ownership and/or stock options in the company. JCC reports other from Pfizer Inc., and is an employee and a stockholder of Pfizer Inc. IG is a fully paid employee of Boehringer Ingelheim International GmbH. CE is Chair of the Government of Canada Interagency Advisory Panel on Research Ethics. LM reports non-financial support from Daiichi-Sankyo and Cell & Gene Therapy Catapult. Morel reports other from UCB. LN reports other from GlaxoSmithKline, including employment and ownership of stock in GSK. RS reports personal fees from BioMed Central and Pfizer, other from NHS England, NHSx, NDC, NCRI, NIHR, MRC CTU, GeL, Glasgow CTU, UCLH, LSHTM, Cancer Research UK, Macmillan, Warwick University, Warwick CTU and University of Birmingham. AW reports grants from NIHR and Innovate UK. All other authors have completed the ICMJE uniform disclosure form and declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years, no other relationships or activities that could appear to have influenced the submitted work.

Figures

**Figure 1**
Proximal and distal effects of therapy on patient symptoms and quality of life. Adapted from Wilson and Cleary.

**Figure 2**
Example schedule of patient-reported outcome (PRO) assessments in the Trans Tasman Radiation Oncology Group 11.03 P-Lung GP Trial. QoL, quality of life.

**Figure 3**
Example schedule of patient-reported outcome assessments in the MRC SUPREMO TRIAL (BIG 2–04). BNP, B-type natriuretic peptide; QoL, quality of life.

**Figure 4**
Flow diagram schedule of patient-reported outcome assessments in the MRC SUPREMO TRIAL (BIG 2–04). BNP, B-type natriuretic peptide; QoL, quality of life.

**Figure 5**
Resources to promote high-quality patient-reported outcomes (PROs) trial design, analysis and dissemination. CONSORT, Consolidated Standards of Reporting Trials; EMA, European Medicines Agency; FDA, Food and Drug Administration; SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials.

See this image and copyright information in PMC

References

1. Chan A-W, Tetzlaff JM, Altman DG, et al. Spirit 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med 2013;158:200–7. 10.7326/0003-4819-158-3-201302050-00583 - DOI - PMC - PubMed
1. Chan A-W, Tetzlaff JM, Gøtzsche PC, et al. Spirit 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 2013;346:e7586. 10.1136/bmj.e7586 - DOI - PMC - PubMed
1. Kyte D, Duffy H, Fletcher B, et al. Systematic evaluation of the patient-reported outcome (pro) content of clinical trial protocols. PLoS One 2014;9:e110229. 10.1371/journal.pone.0110229 - DOI - PMC - PubMed
1. Mercieca-Bebber R, Friedlander M, Kok P-S, et al. The patient-reported outcome content of international ovarian cancer randomised controlled trial protocols. Qual Life Res 2016;25:2457–65. 10.1007/s11136-016-1339-x - DOI - PubMed
1. Kyte D, Retzer A, Ahmed K. Systematic evaluation of patient-reported outcome protocol content and reporting in cancer trials. 111. JNCI: Journal of the National Cancer Institute, 2019: 1170–8. - PMC - PubMed

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SPIRIT-PRO Extension explanation and elaboration: guidelines for inclusion of patient-reported outcomes in protocols of clinical trials

Affiliations

SPIRIT-PRO Extension explanation and elaboration: guidelines for inclusion of patient-reported outcomes in protocols of clinical trials

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous