‘Cohort multiple RCT’ design
workshop
Clare Relton & Jon Nicholl
School of Health and Related Research (ScHARR)
Faculty of Medicine
University of Sheffield
c.relton@sheffield.ac.uk
j.nicholl@sheffield.ac.uk
Purpose of workshop
• Share knowledge, experiences and ideas
Programme
10.35
Introduction to the cmRCT design
11.00
Current research using the design
12.25
Panel Q&A
12.40
LUNCH
13.40
How to analyse cmRCTs
13.50
Talking Circles I & II (35 mins each)
15.00
Tea/coffee
15.20
Plenary feedback/ Panel discussion
16.30
End
Housekeeping
• Exits
• Loos
• Name
• No mobiles
• Workshop information
• Talking circle topics
Backstory
Introduction to cmRCT design
• Problems with standard designs
• cmRCT design defined
• Differences with other designs
• Benefits
• Most suited to.....
Pragmatic trials
• ‘pragmatic’ first applied to clinical trials by
Schwartz & Lellouch (1967) who made the
distinction between:
• explanatory trials (which aim to further
knowledge as to how and why)
• pragmatic/practical trials (which aim to
inform healthcare decisions within routine
practice).
Problems with standard designs
• poor recruitment rates – implications for cost,
validity, reliability, comparability of the results
• informed consent barrier to recruitment (Ross, 1999)
• unrepresentative recruited population
• patient & clinician treatment experiences altered
• lack of long term outcomes
• poor external validity....
Components of cmRCT
• *1 Cohort
• * 2 Random selection
• * 3 Informed consent – patient centred
* 1: Cohort
• Recruit observational cohort of
patients
• Regular outcome measurement for
whole cohort
* 2: Random selection
• Capacity for multiple RCTs over time
• For each RCT
• eligible patients identified from which
some randomly selected to be offered
the intervention
• Outcomes of randomly selected patients
compared to not randomly selected.
* 3: Informed consent
• Patient information and consent
replicate real world routine healthcare
i.e. patients are not told about
treatment that they might not receive
‘Cohort multiple RCT’ design
Relton, Torgerson, O’Cathain & Nicholl.
BMJ 2010;340:c1066
Copyright ©2010 BMJ Publishing Group Ltd.
Based on (Zelen) randomised
consent design
• Reviews: Schellings 2006, Adamson 2006
10/04/2015
Differences: cmRCT & other designs
*1: Cohort
*2: Randomisation
*3: Informed Consent – patient centred
*1. Cohort
• Characterised/ phenotyped population’
• Contacted again
• Use their data comparatively
• Access to routine health records
• Facility for multiple trials
*2. Randomisation
Something that is ‘done’ to everyone?
Random allocation of all
Or
Random selection of some
*3. Informed Consent
Memory research
• Many people suffer from poor memory and there are few treatments
available
• However, US research has found that as well as helping lower blood
pressure (Buitrago-Lopez 2011), chocolate (epicatechin) can boost
memory in mice particularly when combined with exercise. University
of Sheffield researchers are now planning a study to measure the
effectiveness of chocolate on memory.
• We (researchers) are looking for people to participate in this research.
If you decide to participate you will be asked to provide information
about your general health and physical activity (using an online form)
and asked to perform a short online memory test once a week for 6
weeks.
• We are not sure if chocolate is more effective than no chocolate.
• Participants will be randomly selected to receive either chocolate or
no chocolate
*3. Informed Consent
Patient centred
• Replicates procedures in routine
healthcare
• Patients not told about treatments that
they are not then offered
• Patients not told that their treatment will be
chosen ‘at random’
Type and timing of information
(standard RCT design)
(I) There is
a treatment
and the
benefits
are… the
risks are …
10/04/2015
(II) …and
there is
research
ongoing…
(III) … and we
want to
observe you….
(IV) …and
we are not
sure which
treatment
is best….
(V) …and
we are
going to
play a
game of
chance’…
Type and timing of information: ‘patient
centred’ as used in ’cmRCT’ design
(III) … and
we want to
observe
you….
(II) …there is
research
ongoing…
10/04/2015
(I) There is
a treatment
and the
benefits
are… the
risks are …
(IV) …and
we are not
sure which
treatment
is best….
(V revised)
…and you
have been
selected at
random to try
it....
Benefits of ‘cohort
multiple RCT’ approach
• Recruitment – improved quantity and more
representative sample
• multiple RCT facility
• long term outcomes as standard
• ongoing information as to the natural history of the
condition and treatment as usual
• increased comparability between each trial conducted
within the cohort
• increased efficiency, particularly for expensive or high
risk interventions (unequal randomisation)
Opportunities
• Open trials with ‘treatment as usual’ as comparator
• Easily measured & collected outcomes
• Clinical conditions where many trials will be conducted
• Chronic conditions
• Highly desired treatments or expensive treatments
Least suited to..
• Closed trial designs with masking or placebo arms
• Research questions with hard to measure and hard to
collect outcomes
• Acute or short term conditions
Examples
• Ongoing
• Funded
Talking circles
• Your topics
• Facilitator
• Report back:
• Issues discussed
• Conclusions reached
• Actions required
Thank you
• Speakers
• Brett Thombs
• Kate Thomas
• CLAHRC – SY
• Sue & Emily