Clinical trials methodology group Simon Gates 9 February 2006

Clinical trials methodology group

Simon Gates

9 February 2006

Agenda

• Presentation

• Discussion

– Format of meetings

– Important issues in trials methodology

– Actions for next meeting (if any)

• AOB

• Finish at 11am

Warwick Emergency Care and Rehabilitation www.warwick.ac.uk/go/emergencycare

Contents

• RCT methodology

– What is included?

– Why is it important?

– What are the major issues?

• Clinical Trials Methodology Group

– What is it for?

– How will it operate?


RCT methodology

What might be included

All aspects, including (not a complete list):

• Trial design

• Obtaining funding

• Ethics and R&D approvals

• Recruitment of clinicians and patients

• Informed consent

• Follow-up

• Outcome measurement

• Statistical methods

• Methods for economic evaluations

• Dissemination and impact of results on clinical practice.


Why is methodology important?

• Should use the best methods (always room for improvement)

• Efficiency: trials need to be conducted by the most cost-effective methods



• Thousands of trials need to be conducted

• Increasing pressure on limited funding

• Improving efficiency will enable more trials to be conducted

• Good for triallists

• Good for patients



• Lots of problems occur during the conduct of RCTs

• Often we do not have evidence about how to solve them

• We should approach these problems in the same way as clinical questions

• Evidence-based approach



• Should aim to use high quality research evidence to solve problems in RCT conduct

• Where possible, we need randomised evidence and systematic reviews


Major methodological issues

• Recruitment of patients

• Retention of patients

• Recruitment and retention of clinicians


Recruitment of patients

• Poor recruitment very common

• Take longer than expected or fail to reach planned sample size

• Results delayed, more expensive, less useful

• Unlikely to get easier (in UK at least)



• In ISIS-2 (streptokinase and aspirin for acute MI), estimated that delays to recruitment resulted in up to 10,000 deaths.

Collins R, Doll R, Peto R. Ethics in clinical trials. In: Williams CJ, editor(s).

Introducing New Treatments For Cancer: Practical, Ethical and Legal Problems .

Chichester: John Wiley, 1992:49-56.



• Not clear what is the best strategy when faced with poor recruitment

• Many possible interventions but little evidence about their effectiveness

• Likely that different strategies are needed in different situations



• Cochrane methodology review

(Mapstone et al 2002)

• 15 studies, all interventions aimed at patients

• Some non-randomised studies or studies of “mock trials”

• RCTs of other interventions needed


Retention of patients

• Losses to follow up always cause a problem

• Potentially introduce bias

• Best to prevent by achieving high follow-up rates

• Difficult in some populations

• Best ways to achieve this unknown


Recruitment & retention of clinicians

• May have major impact on recruitment of patients

• Clinicians may be reluctant to participate if they perceive it will involve extra work

• Or they may agree to participate but fail to recruit any patients


Recruitment & retention of clinicians

• Protocol for Cochrane methodology review (Rendell et al 2005)

• No randomised studies known


Clinical trials methodology group

What is this group for?

• Discussion: Triallists who have particular problems – opportunity to discuss and get input from colleagues

• Research: identify, design and conduct research projects

• Contribute to setting the research agenda for RCT methodology and building up the literature


What research might we do?

• RCTs of interventions to improve trial conduct

• Systematic reviews (e.g. Cochrane methodology reviews)

• Observational studies

• Surveys e.g. of triallists or published literature

• Testing of methods and recommendations for best practice

• Re-analysis of trial data sets


Methodological research

• Potentially very influential

• Assmann et al.

Subgroup analysis and other (mis)uses of baseline data in clinical trials Lancet 355 (9209): 1064-1069

Times Cited: 131

• Hollis S, Campbell F

What is meant by intention to treat analysis? Survey of published randomised controlled trials. BMJ 319 (7211):

670+

Times Cited: 174


How will it work

• Meetings

• Research projects

• Website


Meetings

• Opportunity to discuss particular issues

• At present scheduled for about once every 2 months

• Each meeting to have a specific topic


Meetings - format

• Short presentation outlining the issues

• Discussion

• Action plan

• Feedback/results from ongoing projects


Research projects

• Groups of interested people to develop and run research projects

• Seek funding if necessary

• Report back to the whole group


Website

• Link from Clinical Trials Unit website

• Notes and slides from meetings

• Information and documents for future meetings

• Information about ongoing projects

• Anything else of interest – ideas?


Tasks

• Short paragraph about any ongoing trials methodology projects

• Ideas for topics for next meetings and volunteers to present


Clinical trials methodology group Simon Gates 9 February 2006

Clinical trials methodology group

Agenda

Contents

RCT methodology

What might be included

Major methodological issues

Recruitment of patients

Recruitment of patients

Recruitment of patients

Recruitment of patients

Retention of patients

Recruitment & retention of clinicians

Recruitment & retention of clinicians