Maximising patient reported outcomes in clinical trials

Patient-reported outcomes (PROs) are used in thousands of clinical trials worldwide to provide evidence of efficacy, safety and tolerability of treatments from the patient perspective. These data can provide valuable evidence on the physical, functional and psychological consequences of treatment and, if captured in a scientifically rigorous way, can inform clinical guidelines, health policy and shared-decision making.

Despite their importance, Birmingham BRC members working with international collaborators have identified major issues in PRO study design, implementation, analysis and reporting which hinder use of these data to inform patient care, clinical guidelines and health policy. Our review of cancer portfolio trials identified suboptimal protocols and 38% failed to publish their PRO findings. This means that up to 49,568 trial participants completed PRO data for no discernible purpose; which is unethical and a waste of research resources estimated at £2.4 million.

Birmingham BRC members (led by Professor Mel Calvert) have worked with patient partners and international collaborators including journal editors (BMJ, Lancet, JAMA, JCO), regulatory agencies (EMA, MHRA, FDA), NICE, HRA, funders, ethicists, methodologists and international societies and the ABPI/pharmaceutical industry to develop best practice guidance for PROs in trials to reduce research waste and maximise patient benefit.

This includes: research prioritisation workshops with stakeholders, core outcome set development in collaboration with the COMET Initiative, selection of PROs informed by the COSMIN checklist and patient input, improving trial design (through the development of the SPIRIT-PRO extension, (JAMA, 2018), protocol template and tools for patient partners involved in codesign, minimising missing data, managing PRO Alerts, collaboration with the EORTC led SISAQOL Consortium (Lancet Oncology 2019/2020) to standardise PRO analyses in cancer trials, the transparent reporting of PRO data (using CONSORT-PRO) and maximising research impact. 

Thus far, SPIRIT-PRO has been cited 253 times to date including by authors from the US, Canadian and European regulatory agencies (Lancet Oncology) and in the FDA Oncology Centre Excellence website/Annual Report. SPIRIT-PRO is being implemented by the NIHR Birmingham BRC, international trials groups and big pharma. Industry, international trials units, patient partners, charities, funders and journals are promoting uptake and use, and we currently have tools for patient partners in press.

Prof Calvert is on a steering committee for the PROTEUS consortium to promote international use of guidelines; this received funding from PCORI and Genentech. Prof Calvert and Dr Aiyegbusi are co-Is on an IMI grant awarded 5 million euro to build on work of SISAQOL initiative, and Prof Calvert has been appointed as a NIHR Senior Investigator award and received prestigious US Health Assessment Lab Career achievement award for this and related methodological work on PROs.