'TwiCs' vs standard approaches to trial design
Standard approach to trial design and informed consent
The commonly used approach to randomised controlled trials (RCTs) (both pragmatic and explanatory trials) is that each trial recruits their own standalone population, and recruitment includes 'full disclosure' of information to all potential trial participants prior to randomisation to groups.
At the trial end, the trial population is disbanded … and for the next research question, a new RCT and trial population is recruited. This 'stand alone, full disclosure' approach is often costly in terms of time and resources, and unsuccessful in recruiting the trial population required.
Although the full disclosure approach is required when there is the possibility that participants will receive placebo, this approach does not necessarily make sense when conducting trials which don't use placebos ie.pragmatic trials – trials which aim to inform routine decision making and which compare the trial intervention to the status quo – whatever that might be – standard care, usual care, no care.
TwiCs approach to trial design and informed consent
The Trials within Cohorts (TwiCs) design takes a different approach to the design and conduct of pragmatic trials by utilising cohorts or registers for one or more major functions for trial conduct.
For each RCT, all eligible people in the cohort or register are identified, and then some are randomly selected to be offered trial intervention.
The outcomes in those randomly selected are compared with the outcomes in those who were eligible but not randomly selected; that is, those receiving the status quo – standard care, usual care, no care
A key feature of cmRCT design is that informed consent is ‘patient/person centred’, that is, the process of obtaining patient information and consent aims to replicate that in real world routine health care. In practice this usually (but not always) means that information about the trial is split up and offered to people when it is most relevant for them to receive the information.
Informed consent - tailored versus untailored disclosure
This section describes how each approach trial design approaches informed consent:
What type of information is provided, to whom and when?
What type of consent is sought, from whom and when?
Five types of consent
The consents that are sought from people (and the information given) can be broken down into five categories A, B, C, D, E as described below:
Consent for standard pragmatic RCTs
The standard approach to informed consent for placebo controlled randomised trials seeks all of these consents (A-E) prior to the 'technical' start of the trial (collection of baseline outcome measures).
For pragmatic trials which compare the outcomes of interventions to the status quo (ie usual care), using the standard approach, consents A-D are sought prior to the start of the trial.
All consents are sought from everyone (regardless of their eventual group allocation). This means that all trial participants are given information about the interventions/treatments being trialled, and they are also told that their group allocation will be decided by chance, regardless of whether or not they receive or be offered something other than the status quo after randomisation.
Consent for cmRCTs
A key feature of cohort multiple RCTs (cmRCTs) is that the information provided and the consents sought replicate the informed consent procedures of usual care where possible.
Randomisation to groups occurs without prior consent. Thus (as is the case in usual care) only those who have access to the intervention/treatment being trialled are actually given information about that treatment.