Item: Contribution of MHTMR Co-Investigator (Melanie Calvert) to a Network project on ‘Quality of Life Reporting Standards: Development of a CONSORT Extension’...
Problem: Patient Reported Outcomes (PROs) are increasingly assessed in randomised clinical trials (RCTs) but are often poorly reported. This can hamper the use of PRO data for clinical decision making, in the development of health policy, and can limit the application of trial results in clinical practice.
Action: An MHTMR Co-investigator is the lead researcher for the collaborative project that aims to develop evidence-based guidance for reporting PROs in RCTs with input from key stakeholders: the CONSORT PRO extension.
Outcomes: A total of 422 stakeholders completed a survey on PRO reporting. 29
international stakeholders attended the consensus meeting including: journal editors (BMJ, JAMA, Lancet, Plos Medicine, JCO and CMAJ), methodologists, clinical trialists, policy makers, clinicians, knowledge translation experts, representatives of UK and US funding bodies, industry, and patients. This work has resulted to date in a Lancet commentary, BMJ Blog, Report in the UKCRC Clinical Trials Units Newsletter and additional funding from the Canadian Institutes of Health Research. Knowledge translation activities have included oral presentation at major international conferences and workshops to provide support and training on PRO design, analysis and reporting in RCTs. A final draft of the CONSORT PRO extension is currently under review by stakeholders in advance of submission for publication. The development of the CONSORT PRO extension, endorsement by major journals and knowledge translation activities, will lead to improved PRO reporting and ultimately patient care.
Item: Contribution of MHTMR-funded PhD student research project to National Research Ethics Committee Guidance (Helen Kirkby with supervisors Heather Draper and Melanie Calvert)...
Problem: There is limited evidence on what potential research participants what to know about research. Current information is often lengthy and may not meet participant needs.
Action: The MHTMR-funded PhD research project assessed the feasibility of electronic information provision, including tailored ‘unfolding’ information sheets; where participants can choose to access increasing amounts of information. The amount of information accessed, patient satisfaction and understanding were assessed.
Outcomes: Electronic information is feasible, however, monitoring of data access showed that many participants access very little information and some choose not to access any. These findings could have a major impact on the information that we give to patients in clinical trials in the future. The Midland HTMR is working closely with the National Research Ethics Committee and this work will inform the guidance on information provision for research participants in the UK. The research to date has yielded one publication with several more in preparation:
Kirkby HM, Calvert M, Draper H, Keeley T, Wilson S. What potential research participants want to know about research: a systematic review. http://bmjopen.bmj.com/content/2/3/e000509.full.pdf
The PhD student has secured a job in the Cancer Research UK Clinical Trials Unit at University of Birmingham thereby showing how such funding also results in capacity building.
Item: Contribution of an MHTMR funded PhD student to the analysis of an NIHR-funded RCT (Danielle Burke with supervisors Lucinda Billingham and Alan Girling and in collaboration with MHTMR Co-Investigator Jon Deeks) ...
Problem: PLUTO is an NIHR funded RCT of the use of fetal vesico-amniotic shunting for fetal bladder outflow obstruction, compared to conservative, non-interventional care. Outcomes are pre-natal and perinatal mortality and renal function. The trial was run in the Birmingham Clinical Trials Unit but stopped early because of an inability to recruit, with data only available on 32 maternities. The MHTMR was approached by the Trials Unit to provide methodological advice to the problematic analysis of a trial with such a limited number of patients.
Action: An MHTMR-funded PhD student was able to investigate the utility of Bayesian methods in this scenario. The trial data was analysed used Bayesian methods, combining the trial results with both non-informative priors and elicited expert opinions on the value of the intervention.
Outcomes: The publication of the trial which is currently being prepared for a clinical journal will include results from a Bayesian analysis alongside the classical results. Such analysis enables results to be presented in a way that can be potentially more informative to clinicians than classical results in the situation of small numbers of patients. In addition, application in this specific example has given insight into issues that will be informative to the methodological community, including the impact of differences in expert beliefs, the ability to adjust for confounders in small trials using Bayesian methods, and the impact of censoring and non-compliance on findings.
Item: Contribution of an MHTMR-funded researcher (Lucinda Billingham) to an international initiative in clinical trials...
Problem: The International Rare Cancers Initiative (IRCI) is a collaborative venture between Cancer Research UK, the National Cancer Institute in United States and the European Organisation for Research for Treatment in Cancer. The aim is to run phase III trials in a selection of rare cancers in order to provide unbiased evidence on interventions that could potentially change clinical practice. Standard trial design of such trials is problematic because of the small population pool and therefore alternative methodological approaches need to be considered.
Action: As part of the IRCI, the MHTMR is collaborating with the Institute for Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU) to provide specific advice for the design of trial in penile cancer which they will run. In addition the MHTMR is working more broadly with the IRCI to develop a collaborative platform for all methodologists working within the IRCI.
Outcomes: An outline proposal for the phase III trial in penile cancer which incorporates a Bayesian design has been submitted to Cancer Research UK for funding and was shortlisted for submission as full application in August 2012. The novel Bayesian design aims to ensure that the information obtained from the trial has the potential to change clinical practice even with a small number of patients. The IRCI collaboration of methodologists will ensure sharing of information and ideas regarding this problematic area of clinical trials and thereby will provide guidance on how to design trials in rare diseases in the future.