Patient and Public Involvement (PPI) in outcome selection in breast cancer and nephrology trials
Trials volume 24, Article number: 93 (2023)
We recently reported that according to patients and healthcare professionals in breast cancer and nephrology trials, teams conducting the trials got their choice of primary outcome wrong (72% of the time) more often than they got it right (28% of the time). A Patient and Public Involvement (PPI) representative, co-author of this letter, asked (on Twitter) whether PPI contributors had been involved in the design of the original trials and by extension the outcome selection. The purpose of this study was to answer this question.
In a recently published study, we investigated how important patients (n = 30) and healthcare professionals (n = 12), with experience in the clinical areas of breast cancer and nephrology, consider the outcomes (particularly the primary outcome) measured in a random selection of 20 breast cancer and 24 nephrology published randomised controlled trials . Primary outcomes are deemed the most important outcomes by trial investigators, and the primary outcome is used to determine the sample size for the trial  as well as being the main way to judge whether the intervention is effective or not. Secondary outcomes aid with decision-making by providing additional information but are considered less important .
We found that according to the patients and healthcare professionals, teams conducting breast cancer and nephrology trials got their choice of primary outcome wrong (72% of the time) more often than they got it right (28% of the time) . A Patient and Public Involvement (PPI) representative, co-author of this letter (LL), asked (on Twitter) whether PPI contributors had been involved in the design of the original trials and by extension the outcome selection. We were unable to answer this question.
The purpose of this short research piece is to answer that question. In addition, we wanted to see if the outcome selection in trials involving PPI contributors was more agreeable to patients and healthcare professionals compared to trials that did not have PPI contributors.
The methods used to randomly select the original 44 trials have been described previously . For the current study, the protocol for each of the 44 trials was sought. Trial registration numbers were found for each trial by reviewing the original published research paper and searching clinical trial registries. Any supplementary documents, for example, audio files, diagrams, disclosure forms and tables, available online for trials were also examined for any information related to PPI in the trial.
Trial protocols were readily available for 25 of the research papers: 13 for the breast cancer trials and 12 for the nephrology trials. For the remaining 19 trials, email contact for the corresponding author was located in the published research paper, and contact was made with each corresponding author. Of the 19 corresponding authors emailed, six replied (four replied providing the trial protocol while two did not have access to the protocol and could only provide some information regarding their study that they believed would be useful to our research objectives), nine did not respond, one had moved institute and was not in a position to supply the protocol and the final three could not be contacted as their email addresses were no longer valid. Extracted data were recorded in a MS Excel spreadsheet.
In total, the 44 original publications and 29 associated protocols were examined for this study: 17 for the breast cancer trials and 12 for the nephrology trials. There were also 48 supplementary files examined: 25 for the breast cancer trials and 23 for the nephrology trials. PPI information on the breast cancer trials and nephrology trials are presented in Tables 1 and 2, respectively.
We found no evidence in any of the main trial publications, protocols or any other available trial documents that there was PPI in selecting the outcomes for any of the 20 breast cancer trials or 24 nephrology trials.
PPI information in the original main trial publication
Of the 20 breast cancer publications, two made reference to PPI, one in the results and the other in the discussion. The first mentioned patient involvement in the decision to “…define a situation in which the absolute benefit of chemotherapy would balance its associated side effects” and the second mentioned “decisions made by either patients or physicians” to discontinue treatment due to adverse events. Neither is related to outcome selection.
Of the 24 nephrology publications, there was no mention of PPI. However, the corresponding author of one of the papers stated that there were in fact some PPI as there were “interviews with some patients to test enrolment efficiency but patients were not involved in outcome selection”.
PPI information in the study protocol
Only two of the available 17 breast cancer protocols mentioned PPI. The protocol for one study explicitly mentioned that there was PPI membership on the Trial Steering Committee. The protocol for the second study detailed a PPI event hosted specifically to discuss research participants’ views on the study procedures relating to the collection of identifiable data and follow-up data.
Of the 12 nephrology protocols, there was no mention of PPI. The corresponding author of one protocol wrote in their email, “In generating the protocol we did not specifically ask for patient input, since an existing drug (sodium polystyrene sulfonate) is ingested by patients on a similar schedule and for the same reasons. That drug is not very effective and has known side effects. Our goal was to make the drug much more effective and with fewer side effects. I felt that all of my patients taking the older drug would agree with this goal and the protocol”.
PPI information in supplementary files
There was no PPI information given in any of the other available study files.
PPI in research has the potential to benefit clinical trials by ensuring that the trial design is relevant, ethical and the trial is attractive to possible future participants . PPI makes it more likely that the trial results are relevant to those impacted by a condition and it can also improve recruitment and retention .
Our findings speak volumes about the reality of “patient/person-centred care” and shared decision-making in clinical trials—researchers make the important decisions and do not see the need to check in with the patient. The comment from one corresponding author, “I felt that all of my patients taking the older drug would agree with this goal and the protocol”, exemplifies this. The researcher knows best. Our results confirm the mismatch between policy and the delivery of healthcare along with the way we produce evidence .
We need to ask the question, “Why are the opinions of patients overlooked when the primary purpose of a clinical trial is to offer patients a treatment/therapy that may improve their health and ultimately quality of life?” Excluding those with the greatest stake in the success of a treatment or therapy is a mistake and we argue it produces “bad” research. We recently published a paper on the continuing scandal of poor medical research . We strongly feel that the lack of PPI representation in trial methodology and conduct is adding to this scandal. Patients must be given the opportunity to become involved in all aspects of the trial process to ensure research is relevant, can achieve its full potential for patients and the public and reduce the chance that scarce resources are wasted.
In order to enable authentic involvement, a “space to talk” and a “space to change” must be provided. These spaces welcome the opportunity for all to share dialogue, deal with any tension or disagreements that may arise between PPI contributors and researchers and also adapt in response to contributor feedback in a way that respects and values all types of expertise equally .
Our findings raise questions about the way that PPI is conducted, especially in relation to power and agency. Who decides how involved any PPI group/contributor will be in a trial? [8, 9]. We encourage the trial teams to refer to GRIPP2 , international guidance on reporting of patient and public involvement in health and social care research, when planning their trial. GRIPP2 is a reporting guideline, typically used when the trial is completed. However, using GRIPP2 at the planning and design stage will show the trial team that PPI in all aspects of the trial is encouraged, even expected.
We have highlighted the lack of transparency in relation to how PPI is reported. The lack of PPI information is palpable in the 44 trials included in this study. There are no PPI co-authors, hardly surprising given there was very little PPI involvement generally and none in selecting the outcomes for the trials. We recommend that in future trials, if PPI representatives are part of the trial team, their input should be acknowledged in a meaningful way and co-authorship should be standard practice. This has been previously discussed in the literature [10, 11].
Our original study found that patients and healthcare professionals disagreed with the trial team’s choice of primary outcome 72% of the time . It does not matter how robust the methodology of a trial is or how experienced the research team is, if the outcome that is most important to people living with a disease (and those treating it) is not measured, or not measured to a sufficient degree of certainty, then it is quite possible that the results will be considered irrelevant. We need to ensure that what we measure is meaningful as well as measurable for the trial to support improved healthcare decision-making.
Our 44 included trials are relatively recent (the earliest was published in 2010), but the body of literature supporting the inclusion of patients and the public precedes these [12,13,14,15]. According to an editorial as far back as 2008 , PPI had gained increasing recognition for its potential in various aspects of healthcare activity both in the UK and internationally over the previous decade. The UK standards for public involvement in research were published in 2019, and in our study of 44 international trials, all fall short of these standards .
Availability of data and materials
The 44 protocols used are hyperlinked in the tables.
Treweek S, Miyakoda V, Burke D, Shiely F. Getting it wrong most of the time? Comparing trialists’ choice of primary outcome with what patients and health professionals want. Trials. 2022;23(1):537.
Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. Int J Surg. 2012;10(1):28–55.
Bagley HJ, Short H, Harman NL, Hickey HR, Gamble CL, Woolfall K, et al. A patient and public involvement (PPI) toolkit for meaningful and flexible involvement in clinical trials–a work in progress. Res Involv Engagem. 2016;2(1):1–14.
Sacristán JA, Aguarón A, Avendaño-Solá C, Garrido P, Carrión J, Gutiérrez A, et al. Patient involvement in clinical research: why, when, and how. Patient Prefer Adherence. 2016;10:631.
Papoulias S, Constantina), Callard F. “A limpet on a ship”: spatio-temporal dynamics of patient and public involvement in research. Health Expect. 2021;24(3):810–8.
Pirosca S, Shiely F, Clarke M, Treweek S. Tolerating bad health research: the continuing scandal. Trials. 2022;23(1):458.
Knowles SE, Allen D, Donnelly A, Flynn J, Gallacher K, Lewis A, et al. More than a method: trusting relationships, productive tensions, and two-way learning as mechanisms of authentic co-production. Res Involv Engagem. 2021;7(1):34.
Locock L, Boylan AM, Snow R, Staniszewska S. The power of symbolic capital in patient and public involvement in health research. Health Expect. 2017;20(5):836–44.
Ocloo J, Matthews R. From tokenism to empowerment: progressing patient and public involvement in healthcare improvement. BMJ Qual Saf. 2016;25(8):626–32.
Staniszewska S, Brett J, Simera I, Seers K, Mockford C, Goodlad S, et al. GRIPP2 reporting checklists: tools to improve reporting of patient and public involvement in research. BMJ. 2017;358:j3453.
Scholz B, Bevan A. Toward more mindful reporting of patient and public involvement in healthcare. Res Involv Engagem. 2021;7(1):61.
Oliver S, Armes DG, Gyte G. Public involvement in setting a national research agenda. Patient Patient-Centered Outcomes Res. 2009;2(3):179–90.
Abma TA. Patient participation in health research: research with and for people with spinal cord injuries. Qual Health Res. 2005;15(10):1310–28.
Oliver S, Clarke-Jones L, Rees R, Milne R, Buchanan P, Gabbay J, et al. Involving consumers in research and development agenda setting for the NHS: developing an evidence-based approach; 2004.
Sutton J, Weiss M. Involving patients as advisors in pharmacy practice research: what are the benefits? Int J Pharm Pract. 2008;16(4):231–8.
Staniszewska S, Herron-Marx S, Mockford C. Measuring the impact of patient and public involvement: the need for an evidence base. Int J Qual Health Care. 2008;20(6):373–4.
NIHR. National standards for public involvement. London: INVOLVE; 2018.
We would like to acknowledge our PPI colleagues on Twitter who read and commented on our work, helping bring the importance of PPI in clinical trials to the fore.
There was no direct funding received for this research. The HRB CRF-C at UCC facilitated the placement of an undergraduate BSc Public Health Sciences student, CB, who led this study under supervision. The HRB Clinical Research Facility receives core funding from the Health Research Board, Ireland, and matched funding from University College Cork. The Health Services Research Unit, University of Aberdeen, receives core funding from the Chief Scientist Office of the Scottish Government Health Directorates.
Ethics approval and consent to participate
This was a retrospective study of published materials. Ethics approval was not required.
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ST is an editor-in-chief of Trials. FS is an associate editor of Trials. The other authors declare that they have no competing interests.
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Buckley, C., Treweek, S., Laidlaw, L. et al. Patient and Public Involvement (PPI) in outcome selection in breast cancer and nephrology trials. Trials 24, 93 (2023). https://doi.org/10.1186/s13063-022-06980-9
- Trial methodology
- Clinical trials
- Patient and public involvement/PPI