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Special Communication |

Reporting of Patient-Reported Outcomes in Randomized Trials:  The CONSORT PRO Extension FREE

Melanie Calvert, PhD; Jane Blazeby, MD; Douglas G. Altman, DSc; Dennis A. Revicki, PhD; David Moher, PhD; Michael D. Brundage, MD ; for the CONSORT PRO Group
[+] Author Affiliations

Author Affiliations: Midland Hub for Trials Methodology Research, School of Health & Population Sciences, University of Birmingham (Dr Calvert); ConDuCT Hub for Trials Methodology Research, School of Social and Community Medicine, University of Bristol (Dr Blazeby); and Centre for Statistics in Medicine, University of Oxford (Dr Altman), England; Outcomes Research, United BioSource Corporation, Bethesda, Maryland (Dr Revicki); Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa (Dr Moher); and Cancer Care and Epidemiology, Cancer Research Institute, Queen's University, Kingston (Dr Brundage), Ontario, Canada.


JAMA. 2013;309(8):814-822. doi:10.1001/jama.2013.879.
Text Size: A A A
Published online

The CONSORT (Consolidated Standards of Reporting Trials) Statement aims to improve the reporting of randomized controlled trials (RCTs); however, it lacks guidance on the reporting of patient-reported outcomes (PROs), which are often inadequately reported in trials, thus limiting the value of these data. In this article, we describe the development of the CONSORT PRO extension based on the methodological framework for guideline development proposed by the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network. Five CONSORT PRO checklist items are recommended for RCTs in which PROs are primary or important secondary end points. These recommendations urge that the PROs be identified as a primary or secondary outcome in the abstract, that a description of the hypothesis of the PROs and relevant domains be provided (ie, if a multidimensional PRO tool has been used), that evidence of the PRO instrument's validity and reliability be provided or cited, that the statistical approaches for dealing with missing data be explicitly stated, and that PRO–specific limitations of study findings and generalizability of results to other populations and clinical practice be discussed. Examples and an updated CONSORT flow diagram with PRO items are provided. It is recommended that the CONSORT PRO guidance supplement the standard CONSORT guidelines for reporting RCTs with PROs as primary or secondary outcomes. Improved reporting of PRO data should facilitate robust interpretation of the results from RCTs and inform patient care.

The CONSORT (Consolidated Standards of Reporting Trials) Statement, first published in 1996 and most recently revised in 2010,1,2 provides evidence-based recommendations to improve the completeness of reporting of randomized controlled trials (RCTs). The statement focuses on parallel-group trials, but a number of extensions for reporting other trial designs (cluster, noninferiority, and equivalence), interventions (nonpharmacologic and herbal therapies), and for specific data, such as harms have been developed.3 The CONSORT Statement is endorsed by major journals and editorial groups, such as the International Committee of Medical Journal Editors, and its use has been associated with improved reporting of trials.4

Patient reported outcomes (PROs; Box include health-related quality of life (HRQL), symptoms, utilities, and satisfaction ratings and are defined as assessments that are patient reported rather than observer reported. PRO data from RCTs are increasingly used to inform patient-centered care, clinical decision making, and health policy or reimbursement decisions.57

Box. Glossary

CONSORT Extension

Additional checklist items regarding guidance for reporting patient-reported outcomes (PROs) (supplementing the CONSORT 2010 Statement)

Elaboration of the CONSORT Statement

Further details on the existing CONSORT 2010 guidance as applied to a specific context; in this instance, as applied to randomized controlled trials assessing PROs

Patient-Reported Outcome

An outcome reported directly by patients themselves and not interpreted by an observer; PROs may include patient assessments of health status, quality of life, satisfaction with care or symptoms, or patient-reported adherence to medication

Proxy-Reported Outcome

Proxy reports from caregivers or clinicians cannot be viewed as PROs5; it is recommended that the standards for reporting of proxy outcomes are similar to those recommended for PROs

Primary or Principal Trial Publication

The first publication of the trial results: this will include the results of all primary outcomes prespecified in the protocol for all trial participants; prespecified secondary PROs will also be reported in the primary publication

Secondary Publication of PRO Results

A detailed exploration of PRO results may be provided in a secondary trial publication (published following the primary article).

Health-Related Quality of Life

Health-related quality of life (HRQOL) is a multidimensional concept that usually includes self-report of the way in which physical, emotional, social, or other domains of well-being are affected by a disease or its treatment

Primary Outcome

The most important outcome in a trial, “providing the most clinically relevant and convincing evidence directly related to the primary objective of the trial.”

Secondary Outcomes

These are outcomes prespecified in the protocol to assess additional effects of the intervention and often include PROs; within the secondary PROs, some may be identified as important or key

Important or Key Secondary Patient-Reported Outcomes

Some PRO measures (particularly HRQOL measures) are multidimensional, producing several domain-specific scales. For any particular trial, it is likely that some domains will be more relevant than others, reflecting the expected effect(s) of the trial intervention(s) in the target patient population. These relevant domains constitute the important or key secondary PROs. Ideally, these will be identified a priori, specified as such in the trial protocol, statistical analysis plan, or both and will be the focus of the principal PRO analysis. Because these are linked with hypotheses (see CONSORT PRO Extension 2b), they may be subject to P value adjustment (or α-spending)

The applications of PROs require accurate, valid, and accessible reporting, but this is uncommonly observed. In a review of 794 RCTs only 56% provided a rationale for the selected PRO, 50% included a PRO hypothesis, 28% provided information about missing PROs data, and 64% discussed the PRO findings in the context of the other trial outcomes.8

The aim of this work was to develop an evidence-based extension of the CONSORT statement for reporting patient reported outcomes in RCTs (extensions) and to elaborate on the existing CONSORT 2010 statement specifically as applied to PROs (elaborations). This article describes the methods used to gain consensus on the extensions and elaborations and provides the rationale for each new item and examples of good reporting.

Development of CONSORT PRO Extension

The extension was based on the methodological framework for guideline development proposed by the EQUATOR Network.9 Initial work was led by the International Society for Quality of Life Research (ISOQOL) Reporting Guidelines Task Force and focused on establishing and developing guidance for RCTs with HRQL as an outcome.10 Following feedback from stakeholders the scope of the guidance was expanded to include PROs. The University of Birmingham Ethical Review Board approved the survey and consensus meeting.

Systematic Review of Existing Guidelines and Survey of Key Stakeholders

A detailed description of the systematic review has been previously reported.10 Briefly, the review identified then existing guidelines (until April 2011) for HRQL reporting in RCTs. Titles identified by a Medline literature search were reviewed independently by 2 task force members (M.D.B. and Brenda Bass, MBA, Queens University, Kingston, Ontario), and supplemented by literature identified by a review of article bibliographies. Candidate standards for reporting HRQL outcome data in RCTs were abstracted from eligible articles.10 The literature search was replicated, updating it to January 2013, to identify additional candidate reporting standards that may have been published since the original systematic review.

This process identified 6 potentially relevant articles, although no proposed reporting standards beyond those considered at the CONSORT extension Delphi meeting were identified. The research leading to the development of the reporting standards was originally HRQL focused. The task force received feedback from ISOQOL and other stakeholder groups that the consensus process should be extended to include all PROs in order to explicitly evaluate the applicability of reporting standards to PROs overall, thus allowing generalization of the reporting standards to all clinical trials that included PROs.

Survey of Key Stakeholders

An online survey was created using candidate reporting items taken from the systematic review.10 The survey was first distributed using the membership listings of ISOQOL10 and subsequently to additional stakeholder groups. Survey respondents were asked to rate the importance of each reporting item when HRQL was a primary outcome and a secondary outcome in an RCT of a biomedical intervention. (The survey instrument, stakeholder groups surveyed, and results are available in eAppendix 1).

Development of the Reporting Guideline

The survey results and comments were synthesized into draft reporting guidance by the task force. The draft guidance was sent to all ISOQOL members and debated at the annual conference in Denver, October 2011. Written feedback after the meeting was encouraged. Following feedback the scope of the guidance was broadened to include all PROs and revised draft guidance was produced for discussion at the CONSORT PRO consensus meeting.

Twenty-nine participants attended the 2-day meeting in London, England, in January 2012. The meeting, which was designed to obtain consensus on the content of the CONSORT PRO extension, included journal editors, methodologists, clinical trialists, policymakers, clinicians, knowledge translation experts, representatives of UK and US funding bodies, industry, and patients. An overview of the consensus process is described in eAppendix 2 with examples of the survey results, and the voting process provided in eFigure 1 and eFigure 2, respectively.

CONSORT PRO Checklist Items: Rationale, Examples, and Explanations

The final CONSORT PRO guidance identifies 5 items to be reported in all RCTs in which PROs are a primary or important secondary outcome. Definitions for terms such as important secondary outcome are contained in the glossary (the Box, and exemplified in the eBox). Table 1 lists the 25 items of the CONSORT 2010 checklist (left column) and the 5-item extension relating to PROs (right-hand column prefaced by the letter P). The items specific to PROs are (1) that the PROs be identified as a primary or secondary outcome in the abstract; (2) that a description of the hypothesis and relevant domains be provided (if a multidimensional PRO tool has been used); (3) that evidence of instrument validity and reliability be provided or cited; (4) that the statistical approaches for dealing with missing data be explicitly stated; and (5) that PRO–specific limitations of study findings and generalizability of results to other populations and clinical practice be discussed. Although an extension was deemed unnecessary for a number of existing CONSORT checklist items, an elaboration of items applied to PRO was recommended (Table 1, right-hand column, plain text). Below we provide the rationale for each PROs specific entry in Table 1, with examples of good practice.

Table Graphic Jump LocationTable 1. Information for Reporting Randomized Controlled Trials With Patient reported Outcomes
Item 1b

CONSORT 2010: structured summary of trial design, methods, results, and conclusions.

PRO Extension: The PRO should be identified in the abstract as a primary or secondary outcome.

Example. “The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory questionnaire total score.”11

Explanation. If a PRO is prespecified as a primary or important secondary outcome in the trial, it should be explicitly stated in the abstract to facilitate indexing and identification of studies to inform clinical care and evidence synthesis.

Item 2a

CONSORT 2010: Scientific background and explanation of rationale.

PRO Elaboration: The relevant background and rationale for why PROs were assessed in the RCT should be briefly described.

Example. “Migraine causes severe impairment or bed rest in more than half (57%) of affected people, markedly impairs quality of life both during and between attacks, increases absenteeism and reduces productivity at work, and is associated with increased health care costs(referenced).”12

Explanation. Given the increasing literature on PROs, and the increasing number of validated instruments available to assess them, the Background or Methods section should briefly establish the rationale for including PROs and why the specific outcomes were selected, thus providing appropriate context for the PRO–specific objectives and hypotheses (see item 2b below). When a PRO is a primary study outcome, a more detailed summary of the existing literature regarding its assessments relevant to the study purpose and objectives is helpful.

Item 2b

CONSORT 2010: Specific objectives or hypotheses.

PRO Extension: The PROs hypothesis should be stated and relevant domains identified, if applicable.

Example. “Potential survival benefit needs to be weighed against the burden of treatment. For this reason, HRQOL, a multidimensional construct(referenced) was included as a secondary end point in the EORTC 18991 study . . . The protocol hypothesized that there would be a difference in global HRQOL scale between both arms, showing worse HRQOL in the PEG-IFN-α-2b arm. The remaining HRQOL variables were then examined on an exploratory basis.”13

Explanation. Patient-reported outcome measures may be multidimensional or unidimensional assessing either one or several aspects of health (eg, physical and social function, or symptoms such as fatigue). In addition, PRO measures may assess global health or HRQL at several time points during an RCT. Without a prespecified hypothesis there is a risk of multiple statistical testing and selective reporting of PROs based on statistically significant results. It is recommended that authors report the rationale for the selection of specific patient-reported outcomes and the time frames of interest, including biological or psychosocial evidence for the proposed anticipated benefits or harms where relevant.

Item 6a

CONSORT 2010: Completely defined prespecified primary and secondary outcome measures, including how and when they were assessed.

PRO Extension: Evidence of PRO instrument validity and reliability should be provided or cited, if available.

Example. “The DLQI [Dermatology Life Quality Index] has well-established reliability and validity when used in a dermatology setting(referenced) and is used frequently in clinical trials of psoriasis(referenced).”14

Explanation. Ideally, the validity of all PROs used in RCTs should be established in relation to the study target population and a brief rationale for the choice of PRO instrument in the trial should be provided. This rationale may also include the validity of translated or otherwise culturally specific versions of the instrument where relevant.

There are currently more than 700 PRO measures available for use in trials.15 Clinical use of PRO data requires that the trial results are robust, which depends on a valid and reliable PRO instrument being used appropriately. Evidence should be cited of the reliability and validity of the PRO measure used in the trial so that readers can access this information. If an RCT uses a PRO instrument with psychometric properties that have not yet been published (eg, a new instrument developed for the trial), the authors should provide information on item content of the instrument and evidence regarding its reliability and validity, in an appendix if the article does not allow for such details.16

Item 6a

CONSORT 2010: Completely defined prespecified primary and secondary outcome measures, including how and when they were assessed.

PRO Elaboration: Details of the mode of PRO completion (in particular if a proxy completed the questionnaire on behalf of the patient), and the method of data collection (paper, telephone, electronic, other) should also ideally be provided particularly when the PRO is the primary outcome.

Example. “Participants were asked to provide data at three time points; four, eight, and 12 months post-randomization, using a self completion questionnaire to eliminate any observer bias.”17

Explanation. In some instances it may not be possible for the PRO to be completed directly by the patient. If the outcome has been completed by a proxy, this should be reported so that readers can assess any potential bias or effect on the results. Different methods of data collection may also affect the results and lead to potential bias if used differentially between intervention groups. For example, collecting PROs by telephone or in a face-to-face interview may cause patients to respond in a way that differs from what they would self-report on paper in private.

Item 12a

CONSORT 2010: Statistical methods used to compare groups for primary and secondary outcomes.

PRO Extension: Statistical approaches for dealing with missing data should be explicitly stated for PROs prespecified as primary or important secondary outcomes.

Example. “Analysis of complete cases, last observation carried forward, and imputation of expected and worse scores per time point were provided to check the robustness of the main results.”18

Explanation. Missing trial outcome data leads to reduced power, is a potential source of bias, and can result in misleading results. The level of missing PRO data are often relatively high. In a review of a random selection of RCTs (n = 61) published in leading international journals with HRQL as an outcome, only 10% of studies reported no missing data; in 21%, the level of missing data was unclear; and 36% had in excess of 10% missing data.19 Importantly, PRO data often are not missing at random but in relation to the outcome of interest, for example, improvement or deterioration in health status. Different statistical approaches to dealing with missing data have respective strengths and limitations.2,20 In the example shown above,18 for instance, the “last observation carried forward” method has been criticized by some authors (who offer guidance on these methods for interested readers).21 Thus, in order to allow adjudication of the methods used by the authors, the approach taken should be clearly described and the potential effect on the validity of the PRO findings should be discussed when relevant.2,22,23

Item 13a

CONSORT 2010: For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analyzed for the primary outcome.

PRO Elaboration: The number of participants reporting PRO data at baseline and at subsequent time points should be made transparent.

Example. eFigure 3 is a CONSORT flow diagram that includes the number of participants providing PRO data (available at http://www.jama.com)

Explanation. The CONSORT flow diagram provides readers with an overview of the progress of participants through the phases of an RCT (enrolment, intervention allocation, follow-up, and data analysis). Authors are encouraged to consider how best to report the flow of participants through the trial in relation to PROs, including information on the reason for missing PRO forms, such as lack of questionnaire return, translations unavailable, or other reasons if known (eFigure 3).2427 This information will help readers to interpret the PRO results and assess the potential for bias, particularly when missing data are due to deterioration of health status. Authors may also consider providing this information in a tabulated form,28 produced for each treatment group, or in footnotes of the flow diagram.

Item 15

CONSORT 2010: A table showing baseline demographic and clinical characteristics for each group.

PRO Elaboration: Including baseline PRO data when collected.

Example. See Table 2: Example presentation of baseline PROs data in an RCT.29

Table Graphic Jump LocationTable 2. Example Presentation of Baseline Patient-Reported Outcome Data

Explanation. Baseline PROs data may be used by clinicians and policy makers to assess the relevance and generalizability of trial findings.30

Item 17a

CONSORT 2010: For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval).

PRO Elaboration: for multidimensional PROs, results from each domain and time point specified for analysis.

Example. See Table 3: Example of treatment effects on quality of life outcomes, taken from the report of an RCT comparing 2 interventions for drug-resistant temporal lobe epilepsy.31

Table Graphic Jump LocationTable 3. Example of Treatment Effects on Quality of Life Outcomesa

Explanation. The potential for selective reporting of PROs is increased because study instruments often contain multiple scales and items. In general, it is recommended that all PRO results should be presented alongside other outcome data typically in tabular form. The important PRO secondary outcomes should be presented in the main publication in order to facilitate the clinical integration of the important findings with other prespecified outcomes. Additional PROs or the components of composite PRO scores should be presented in the main publication where possible, as an eAppendix or expanded secondary report to reduce selective reporting of significant results and to ensure that PRO evidence is available to inform clinical practice and evidence synthesis.32,33

Item 20

CONSORT 2010: Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses.

Item 21

CONSORT 2010: Generalizability (external validity, applicability) of the trial findings.

PRO Extension: PRO–specific limitations and implications for generalizability of study findings and clinical practice.

Examples. “A potential source of bias was the overall amount of missing HRQL forms over the course of the assessment period, with more missing data in the Gemcitibine arm . . . this problem tempers our ability to generalize these longer-term effects to future patients.”34

“Non-attenders at one year, however, might have had a different symptom profile and overall quality of life than attenders, and therefore some degree [of] selection bias is possible.”35

Explanation. In addition to the design and conduct issues relevant to the generalizability of the RCT overall, several PRO–specific limitations (including both patient- and center-level characteristics) may affect generalizability of the PRO results. For example, if PRO assessments are limited to a subgroup of the main trial population, it is recommended to provide reasons why patients were excluded from the PRO study (such as where appropriate translations were unavailable). If PRO data are missing, it is particularly important to discuss the potential reasons in relation to the clinical context and implications for interpretation, as well as the interpretation of any supportive (eg, sensitivity) analyses undertaken. Furthermore, because many of the previously described methodological details of PROs assessment may affect the RCT results, the potential influence of these details on the interpretation of the PRO findings is recommended where suspected to be important.

Item 22

CONSORT 2010: Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence.

PRO Elaboration: Patient reported outcome data should be interpreted in relation to clinical outcomes including survival data, where relevant.

Example. “Patients who received cetuximab experienced significantly less HRQL deterioration and a longer time before clinically significant deterioration occurred. These results are important, because . . . although cetuximab monotherapy . . . results in improved overall survival, progression free survival, recurrence rates and disease control rate . . . the magnitude of these benefits . . . was not large.”

Conclusion: “[C]etuximab offers important HRQL benefits and survival benefits for pre-treated patients with advanced CRC.”36

Explanation. The clinical significance of PRO results is often not discussed in RCT reports but should be interpreted in relation to other important clinical outcomes such as survival, especially in trials for which there are clinically relevant trade-offs between PROs and survival outcomes.37 Further interpretation of PRO results may include discussion of a minimal important change or a responder definition (if validated for the particular PRO instrument used in the study), comparison with other similar RCTs, or linking the clinical significance of the PRO results to the other trial outcomes such as toxicity rates.

CONSORT PRO aims to promote transparent reporting of RCTs in which PROs are primary or important secondary outcomes. Improved reporting will facilitate interpretation of PRO results for use in clinical practice, as described in User Guides23,38 and inform evidence synthesis and health policy. Transparent reporting will facilitate comprehension of limitations of the data and potential sources of bias. The primary trial publication is often the only opportunity to report PRO data such that it can be interpreted in the context of the other clinical trial findings. Presentation of PRO data in stand-alone articles, which may be published months or years after the main trial report, can be a barrier to patient reported outcome data uptake. Therefore, we recommend that authors report primary or important secondary outcome for PRO results according to the 5 new items described in this article in the primary publication and that journals provide appropriate mechanisms to facilitate optimal PRO reporting (for example templates and online appendices). The CONSORT PRO checklist also elaborates how specific components of the existing CONSORT 2010 Statement may be implemented in relation to PROs.

We encourage authors, peer reviewers, and readers to use CONSORT PRO in conjunction with the CONSORT 2010 Statement and other explanation and elaboration articles (appropriate for the trial design, intervention, and outcomes).13 The CONSORT Group is considering consolidating some of the guidance statements, to facilitate uptake by authors who may find the number of available checklists difficult to implement.

In this extension we make reference to important or key secondary outcomes, which may be defined as prespecified PRO domains in the protocol that have hypothesized effects or for which the statistical power and sample size may have been taken into account. It is recognized that these definitions are not widely used and more work is needed to provide standardized terms for secondary outcomes (clinical and PROs)(eBox). A further issue that arose during the consensus meeting is that the PRO extension to item P12a, “Statistical approaches for dealing with missing data explicitly stated,” is relevant for other RCT outcomes. We encourage authors to consider reporting this type of information for all outcomes.

We developed CONSORT PRO rigorously according to current standards for developing reporting guidelines.9 Like other reporting guidelines, the development of CONSORT PRO is a work in progress. We will continue to monitor the literature to help guide us in any further development of this CONSORT extension. Similarly, we encourage readers to provide feedback regarding this reporting guidance and how it might be further refined.

We encourage journals to modify their “Instructions for Authors” to endorse the CONSORT PRO extension. We plan to disseminate CONSORT PRO to journals currently known to endorse CONSORT 201039 and other relevant groups, such as the EQUATOR Network.40 We plan to evaluate whether the CONSORT PRO extension is having its intended effect, namely improved completeness of reporting RCTs in which PROs are a primary or important secondary outcome.

Finally, although these guidelines focus on PRO reporting, the design of trials assessing PROs may also be improved. We recommend that trialists consider the useful guidance from the US Food and Drug Administration (FDA) on the development, validation, and implementation of PRO measures and their analysis in RCTs.5 Trialists should consider PRO-specific protocol requirements in relation to the FDA guidance and more general recommendations on RCT design from the Standard protocol Items: Recommendations for Interventional Trials (SPIRIT) initiative.40,41

Corresponding Author: Michael D. Brundage, MD, Queen's Cancer Research Institute, Cancer Care and Epidemiology, Level 2, 10 Stuart St, Kingston, ON K7L 3N6 Canada (michael.brundage@krcc.on.ca).

Author Contributions: Drs Calvert and Brundage had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: All authors.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: All authors.

Obtained funding: Calvert, Blazeby,Revicki, Moher, Brundage.

Study supervision: Calvert, Blazeby, Revicki, and Brundage.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Calvert reported that she has served as a consultant to Amgen. No other disclosures were reported.

The CONSORT PRO Group Contributors to CONSORT PRO Extension/Elaboration 2012: ISOQOL Reporting Guidelines Task Force: Dr Brundage, Queen's University, Kingston, Ontario, Canada (chair): Dr Calvert, University of Birmingham, England; Dr Blazeby, University of Bristol, England; Dr Moher, Ottawa Hospital Research Institute, Ontario; Dr Revicki, Outcomes Research, United Biosource Corp, Bethesda, Maryland; Jane Scott, Patient Reported Outcomes, Janssen Global Services, Manchester, England; Dr Fabio Efficace, GIMEMA, Rome, Italy; Henrica de Vet, PhD, Vrije Universeit Medical Center, the Netherlands; Susan Yount, PhD, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Claire Snyder, PhD, The Johns Hopkins School of Medicine, Baltimore, Maryland; Madeleine King, PhD, University of Sydney, Australia; Cindy Lam, PhD, The University of Hong Kong; Helen Duffy, BA(Hons), University of Birmingham, England; and Brenda Bass, MBA, Queen's University, Kingston, Ontario, Canada.

Funding/Support: This work was supported by the UK Medical Research Council Hubs for Trials Methodology Research and the Canadian Institutes of Health Research. Dr Moher is funded, in part, through a University of Ottawa Research Chair. Dr Altman is supported by grant C5529 from Cancer Research UK. Dr Brundage is supported by a Cancer Care Ontario Research Chair award.

Role of the Sponsor: None of the sponsors had any involvement in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

Disclaimer: Robert M. Golub, MD, JAMA Deputy Editor, participated in the CONSORT PRO meeting in London but was not involved in the JAMA editorial evaluation of or decision to publish this article.

Additional Contributions: Members of the CONSORT PRO Group attended the meeting, except for those noted below, and provided input on and review of the revised checklist and text of this article. Dr Altman, Centre for Statistics in Medicine, University of Oxford, Oxford, England; Ethan Basch, MD, Memorial Sloan-Kettering Cancer Center, New York, New York; Peter Davidson, MD, Health Technology Assessment, National Institute for Health Research Evaluation, Trials and Studies Coordination Centre, University of Southampton, England; Michael Drummond, MD, Value in Health, Lawrenceville, NJ; Martin Eccles, MD, School of Population and Health Sciences, Newcastle University, England; Cynthia J. Girman, MD, Department of Epidemiology, University of North Carolina, and Merck Research Laboratories, Chapel Hill; Robert M. Golub, MD, JAMA, Chicago, Illinois; Paul B. Jacobsen, PhD, Journal of Clinical Oncology, Boston, Massachusetts; Astrid James, MD, Lancet, London, England; Xavier Luria, MD, Safety and Efficacy of Medicines, European Medicines Agency, London, England; Donald Patrick, PhD, MSPH, International Society for Pharmacoeconomics and Outcomes Research, Lawrenceville, NJ; Richard Stephens, patient representative, England; Andrew Stevens, National Institute for Health and Clinical Excellence appraisals committee, London, England; Sharon Straus, MD, Knowledge Translation Program, Li Ka Shing, Knowledge Institute, St Michael's Hospital, Toronto, Ontario; Emma Veitch, MD, PLoS Medicine, London, England; Rosalie Viney, MD, Centre for Health Economics Research and Evaluation, University of Technology Sydney, Australia; Deborah Watkins Bruner, MD, Emory University, Atlanta, Georgia. Contributors to CONSORT PRO Extension/Elaboration 2012 who did not attend the London meeting: Trish Groves, MD, BMJ open access, BMJ, London, England; Maria Von Hildebrand, Carer Representative, England.

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Marshall M, Lockwood A, Bradley C, Adams C, Joy C, Fenton M. Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia.  Br J Psychiatry. 2000;176:249-252
PubMed   |  Link to Article
Chalder M, Wiles NJ, Campbell J,  et al.  Facilitated physical activity as a treatment for depressed adults: randomised controlled trial.  BMJ. 2012;344:e2758
PubMed  |  Link to Article   |  Link to Article
Bottomley A, Biganzoli L, Cufer T,  et al; European Organization for Research and Treatment of Cancer Breast Cancer Group.  Randomized, controlled trial investigating short-term health-related quality of life with doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: European Organization for Research and Treatment of Cancer Breast Cancer Group, Investigational Drug Branch for Breast Cancer and the New Drug Development Group Study.  J Clin Oncol. 2004;22(13):2576-2586
PubMed   |  Link to Article
Fielding S, Maclennan G, Cook JA, Ramsay CR. A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes.  Trials. 2008;9:51
PubMed   |  Link to Article
Sterne JAC, Davey Smith G. Sifting the evidence—what's wrong with significance tests?  BMJ. 2001;322(7280):226-231
PubMed   |  Link to Article
Fairclough DL. Design and Analysis of Quality of Life Studies in Clinical Trials. New York, NY: Chapman and Hall/CRC; 2002
Fairclough DL. Patient reported outcomes as endpoints in medical research.  Stat Methods Med Res. 2004;13(2):115-138
PubMed   |  Link to Article
Guyatt GH, Naylor CD, Juniper E, Heyland DK, Jaeschke R, Cook DJ.Evidence-Based Medicine Working Group.  Users' Guides to the medical literature, XII: how to use articles about health-related quality of life.  JAMA. 1997;277(15):1232-1237
PubMed   |  Link to Article
Jellema P, van der Windt DA, van der Horst HE, Twisk JW, Stalman WA, Bouter LM. Should treatment of (sub)acute low back pain be aimed at psychosocial prognostic factors? cluster randomised clinical trial in general practice.  BMJ. 2005;331(7508):84-91
PubMed   |  Link to Article
Moinpour CM, Donaldson GW, Liepa AM, Melemed AS, O’Shaughnessy J, Albain KS. Evaluating health-related quality-of-life therapeutic effectiveness in a clinical trial with extensive nonignorable missing data and heterogeneous response: results from a phase III randomized trial of gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer.  Qual Life Res. 2012;21(5):765-775
PubMed   |  Link to Article
Mutrie N, Campbell AM, Whyte F,  et al.  Benefits of supervised group exercise programme for women being treated for early stage breast cancer: pragmatic randomised controlled trial.  BMJ. 2007;334(7592):517
PubMed   |  Link to Article
van der Roer N, van Tulder M, Barendse J, Knol D, van Mechelen W, de Vet H. Intensive group training protocol versus guideline physiotherapy for patients with chronic low back pain: a randomised controlled trial.  Eur Spine J. 2008;17(9):1193-1200
PubMed   |  Link to Article
de Boer AG, van Lanschot JJ, van Sandick JW,  et al.  Quality of life after transhiatal compared with extended transthoracic resection for adenocarcinoma of the esophagus.  J Clin Oncol. 2004;22(20):4202-4208
PubMed   |  Link to Article
Davies HE, Mishra EK, Kahan BC,  et al.  Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial.  JAMA. 2012;307(22):2383-2389
PubMed   |  Link to Article
Sculpher MJ, Pang FS, Manca A,  et al.  Generalisability in economic evaluation studies in healthcare: a review and case studies.  Health Technol Assess. 2004;8(49):iii-iv, 1-192
PubMed
Engel J Jr, McDermott MP, Wiebe S,  et al; Early Randomized Surgical Epilepsy Trial (ERSET) Study Group.  Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial.  JAMA. 2012;307(9):922-930
PubMed   |  Link to Article
Freemantle N, Calvert MJ. Interpreting composite outcomes in trials.  BMJ. 2010;341:c3529
PubMed  |  Link to Article   |  Link to Article
Chan AW, Hróbjartsson A, Haahr MT, Gøtzsche PC, Altman DG. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles.  JAMA. 2004;291(20):2457-2465
PubMed   |  Link to Article
Moinpour CM, Vaught NL, Goldman B,  et al.  Pain and emotional well-being outcomes in Southwest Oncology Group–directed intergroup trial S0205: a phase III study comparing gemcitabine plus cetuximab versus gemcitabine as first-line therapy in patients with advanced pancreas cancer.  J Clin Oncol. 2010;28(22):3611-3616
PubMed   |  Link to Article
Welton AJ, Vickers MR, Kim J,  et al; WISDOM team.  Health related quality of life after combined hormone replacement therapy: randomised controlled trial.  BMJ. 2008;337:a1190
PubMed  |  Link to Article   |  Link to Article
Au HJ, Karapetis CS, O’Callaghan CJ,  et al.  Health-related quality of life in patients with advanced colorectal cancer treated with cetuximab: overall and KRAS-specific results of the NCIC CTG and AGITG CO.17 Trial.  J Clin Oncol. 2009;27(11):1822-1828
PubMed   |  Link to Article
Cocks K, King MT, Velikova G, Fayers PM, Brown JM. Quality, interpretation and presentation of European Organisation for Research and Treatment of Cancer quality of life questionnaire core 30 data in randomised controlled trials.  Eur J Cancer. 2008;44(13):1793-1798
PubMed   |  Link to Article
Sprangers MA, Moinpour CM, Moynihan TJ, Patrick DL, Revicki DA.Clinical Significance Consensus Meeting Group.  Assessing meaningful change in quality of life over time: a users' guide for clinicians.  Mayo Clin Proc. 2002;77(6):561-571
PubMed   |  Link to Article
 Equator Network website. http://www.equator-network.org. Accessed May 10, 2012
Chan A-W, Tetzlaff JM, Altman DG,  et al.  SPIRIT 2013 Statement: Defining standard protocol items for clinical trials.  Ann Intern Med. 2013;158(3):200-207
PubMed   |  Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1. Information for Reporting Randomized Controlled Trials With Patient reported Outcomes
Table Graphic Jump LocationTable 2. Example Presentation of Baseline Patient-Reported Outcome Data
Table Graphic Jump LocationTable 3. Example of Treatment Effects on Quality of Life Outcomesa

References

Schulz KF, Altman DG, Moher D.CONSORT Group.  CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials.  BMJ. 2010;340:c332
PubMed   |  Link to Article
Moher D, Hopewell S, Schulz KF,  et al.   CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials.  BMJ. 2010;340:c869
PubMed   |  Link to Article
 CONSORT Group website. http://www.consort-statement.org. Accessed May 29, 2012
Turner L, Shamseer L, Altman DG,  et al.  Consolidated standards of reporting trials (CONSORT) and the completeness of reporting of randomised controlled trials (RCTs) published in medical journals.  Cochrane Database Syst Rev. 2012;11:MR000030
PubMed
FDA Guidance on Patient Reported Outcomes (PROs). http://www.ispor.org/workpaper/FDA%20PRO%20Guidance.pdf. Accessed April 25, 2012
Basch E. The missing voice of patients in drug-safety reporting.  N Engl J Med. 2010;362(10):865-869
PubMed   |  Link to Article
Lipscomb J, Reeve BB, Clauser SB,  et al.  Patient-reported outcomes assessment in cancer trials: taking stock, moving forward.  J Clin Oncol. 2007;25(32):5133-5140
PubMed   |  Link to Article
Brundage M, Bass B, Davidson J,  et al.  Patterns of reporting health-related quality of life outcomes in randomized clinical trials: implications for clinicians and quality of life researchers.  Qual Life Res. 2011;20(5):653-664
PubMed   |  Link to Article
Moher D, Schulz KF, Simera I, Altman DG. Guidance for developers of health research reporting guidelines.  PLoS Med. 2010;7(2):e1000217
PubMed   |  Link to Article
Brundage M, Blazeby J, Revicki D,  et al.  Patient-reported outcomes in randomized clinical trials: development of ISOQOL reporting standards [published online ahead of print September 18, 2012].  Qual Life Res
PubMed  |  Link to Article
Bischoff EW, Akkermans R, Bourbeau J, van Weel C, Vercoulen JH, Schermer TR. Comprehensive self management and routine monitoring in chronic obstructive pulmonary disease patients in general practice: randomised controlled trial.  BMJ. 2012;345:e7642
PubMed  |  Link to Article   |  Link to Article
Holroyd KA, Cottrell CK, O’Donnell FJ,  et al.  Effect of preventive (beta blocker) treatment, behavioral migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial.  BMJ. 2010;341:c4871
PubMed   |  Link to Article
Bottomley A, Coens C, Suciu S,  et al.  Adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma: a phase III randomized controlled trial of health-related quality of life and symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group [published correction in J Clin Oncol. 2009;27(27):4630].  J Clin Oncol. 2009;27(18):2916-2923
PubMed   |  Link to Article
Revicki DA, Willian MK, Menter A,  et al.  Impact of adalimumab treatment on patient-reported outcomes: results from a Phase III clinical trial in patients with moderate to severe plaque psoriasis.  J Dermatolog Treat. 2007;18(6):341-350
PubMed   |  Link to Article
 Patient-Reported Outcome and Quality of Life Instruments Database (PROQOLID) website. http://www.proqolid.org. Accessed September 5, 2012
Marshall M, Lockwood A, Bradley C, Adams C, Joy C, Fenton M. Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia.  Br J Psychiatry. 2000;176:249-252
PubMed   |  Link to Article
Chalder M, Wiles NJ, Campbell J,  et al.  Facilitated physical activity as a treatment for depressed adults: randomised controlled trial.  BMJ. 2012;344:e2758
PubMed  |  Link to Article   |  Link to Article
Bottomley A, Biganzoli L, Cufer T,  et al; European Organization for Research and Treatment of Cancer Breast Cancer Group.  Randomized, controlled trial investigating short-term health-related quality of life with doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: European Organization for Research and Treatment of Cancer Breast Cancer Group, Investigational Drug Branch for Breast Cancer and the New Drug Development Group Study.  J Clin Oncol. 2004;22(13):2576-2586
PubMed   |  Link to Article
Fielding S, Maclennan G, Cook JA, Ramsay CR. A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes.  Trials. 2008;9:51
PubMed   |  Link to Article
Sterne JAC, Davey Smith G. Sifting the evidence—what's wrong with significance tests?  BMJ. 2001;322(7280):226-231
PubMed   |  Link to Article
Fairclough DL. Design and Analysis of Quality of Life Studies in Clinical Trials. New York, NY: Chapman and Hall/CRC; 2002
Fairclough DL. Patient reported outcomes as endpoints in medical research.  Stat Methods Med Res. 2004;13(2):115-138
PubMed   |  Link to Article
Guyatt GH, Naylor CD, Juniper E, Heyland DK, Jaeschke R, Cook DJ.Evidence-Based Medicine Working Group.  Users' Guides to the medical literature, XII: how to use articles about health-related quality of life.  JAMA. 1997;277(15):1232-1237
PubMed   |  Link to Article
Jellema P, van der Windt DA, van der Horst HE, Twisk JW, Stalman WA, Bouter LM. Should treatment of (sub)acute low back pain be aimed at psychosocial prognostic factors? cluster randomised clinical trial in general practice.  BMJ. 2005;331(7508):84-91
PubMed   |  Link to Article
Moinpour CM, Donaldson GW, Liepa AM, Melemed AS, O’Shaughnessy J, Albain KS. Evaluating health-related quality-of-life therapeutic effectiveness in a clinical trial with extensive nonignorable missing data and heterogeneous response: results from a phase III randomized trial of gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer.  Qual Life Res. 2012;21(5):765-775
PubMed   |  Link to Article
Mutrie N, Campbell AM, Whyte F,  et al.  Benefits of supervised group exercise programme for women being treated for early stage breast cancer: pragmatic randomised controlled trial.  BMJ. 2007;334(7592):517
PubMed   |  Link to Article
van der Roer N, van Tulder M, Barendse J, Knol D, van Mechelen W, de Vet H. Intensive group training protocol versus guideline physiotherapy for patients with chronic low back pain: a randomised controlled trial.  Eur Spine J. 2008;17(9):1193-1200
PubMed   |  Link to Article
de Boer AG, van Lanschot JJ, van Sandick JW,  et al.  Quality of life after transhiatal compared with extended transthoracic resection for adenocarcinoma of the esophagus.  J Clin Oncol. 2004;22(20):4202-4208
PubMed   |  Link to Article
Davies HE, Mishra EK, Kahan BC,  et al.  Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial.  JAMA. 2012;307(22):2383-2389
PubMed   |  Link to Article
Sculpher MJ, Pang FS, Manca A,  et al.  Generalisability in economic evaluation studies in healthcare: a review and case studies.  Health Technol Assess. 2004;8(49):iii-iv, 1-192
PubMed
Engel J Jr, McDermott MP, Wiebe S,  et al; Early Randomized Surgical Epilepsy Trial (ERSET) Study Group.  Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial.  JAMA. 2012;307(9):922-930
PubMed   |  Link to Article
Freemantle N, Calvert MJ. Interpreting composite outcomes in trials.  BMJ. 2010;341:c3529
PubMed  |  Link to Article   |  Link to Article
Chan AW, Hróbjartsson A, Haahr MT, Gøtzsche PC, Altman DG. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles.  JAMA. 2004;291(20):2457-2465
PubMed   |  Link to Article
Moinpour CM, Vaught NL, Goldman B,  et al.  Pain and emotional well-being outcomes in Southwest Oncology Group–directed intergroup trial S0205: a phase III study comparing gemcitabine plus cetuximab versus gemcitabine as first-line therapy in patients with advanced pancreas cancer.  J Clin Oncol. 2010;28(22):3611-3616
PubMed   |  Link to Article
Welton AJ, Vickers MR, Kim J,  et al; WISDOM team.  Health related quality of life after combined hormone replacement therapy: randomised controlled trial.  BMJ. 2008;337:a1190
PubMed  |  Link to Article   |  Link to Article
Au HJ, Karapetis CS, O’Callaghan CJ,  et al.  Health-related quality of life in patients with advanced colorectal cancer treated with cetuximab: overall and KRAS-specific results of the NCIC CTG and AGITG CO.17 Trial.  J Clin Oncol. 2009;27(11):1822-1828
PubMed   |  Link to Article
Cocks K, King MT, Velikova G, Fayers PM, Brown JM. Quality, interpretation and presentation of European Organisation for Research and Treatment of Cancer quality of life questionnaire core 30 data in randomised controlled trials.  Eur J Cancer. 2008;44(13):1793-1798
PubMed   |  Link to Article
Sprangers MA, Moinpour CM, Moynihan TJ, Patrick DL, Revicki DA.Clinical Significance Consensus Meeting Group.  Assessing meaningful change in quality of life over time: a users' guide for clinicians.  Mayo Clin Proc. 2002;77(6):561-571
PubMed   |  Link to Article
 Equator Network website. http://www.equator-network.org. Accessed May 10, 2012
Chan A-W, Tetzlaff JM, Altman DG,  et al.  SPIRIT 2013 Statement: Defining standard protocol items for clinical trials.  Ann Intern Med. 2013;158(3):200-207
PubMed   |  Link to Article

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Supplemental Content

Calver M, Blazeby J, altman DG, Revicki DA, Moher D, Brundage, MD. Reporting of Patient-Reported Outcomes in Randomized Trials: The CONSORT PRO Extension. JAMA.

eAppendix 1. Development of CONSORT PRO Reporting Guideline

eFigure 1. Stakeholder Survey Results

eFigure 2. PRO Hypotheses Statement Voting Results

eFigure 3. CONSORT Flow Diagram Including PRO

eBox. Example: Important Secondary PRO Outcome

eApendix 2. CONSORT Stakeholder Survey Questions

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