Question 10

College answer

Aim: To explore candidate understanding of a specific type of research methodology which has been important in recent times.
Key Sources include: This is a repeat question of paper 2022.1 Q27. CanMEDS Scholar.

Discussion: This question was a straightforward and a pure knowledge-based question that had been asked in the very recent past. Candidates’ responses would have been improved with more core knowledge of this important trial design.
Candidates generally answered reasonably well, and those who used the headings suggested were generally able to pass the question. Some candidates had little to say or did not attempt the question. Candidates are encouraged to attempt every question and are reminded there is no negative marking.
There are many points in the advantages and disadvantages that can be answered from first principles, and these were enough to pass the question, for example, commenting on the complexity of trial design, familiarity with the general medical cohort to interpret results, logistical challenges, efficiency, and flexibility. The better candidates were able to demonstrate more nuanced understanding of platform trials, such as the need to increase sample size when multiple trial arms were included, and the possibility that progressive changes to the control arm might make it hard to compare newer arms of the trial to the original cohort.
 

Discussion

Let no one say they stopped repeating questions. This SAQ is basically identical to Question 27 from the first paper of 2022. 

• Platform trials are an example of adaptive multiarm multistage trials:
  • Adaptive trials undego regular interim analysis and can change the sample size of the treatment group
  • Multiarm multistage trials are adaptive trials with multiple treatment arms compared against the same control group, with the option of dropping an underperforming arm
  • Platform trials are the same design, but with the option of adding arms and adjusting the size of the control group
• Advantages:
  • "Disease-focused" instead of "intervention-focused
  • Efficient use of study resources (as compared to running an individual trial for each of the interventions in each arm)
  • Avoids redundant duplication of design and infrastructure
  • Easier to compare interventions (instead of comparing between different trials with different methodologies)
  • Resistant to obsolescence: novel developments can be incorporated into the study protocol, maintaining currency 
  • Perpetual: the trial never actually needs to finish; new arms can be added and old arms removed under the same master protocol
  • Minimises the size of the control group: this is ethically better, as trial treatment is being provided to the maximum number of potential beneficiaries
  • A platform trial can declare one treatment superior to the others
  • Interim sample size adjustment can prevent underpowered results
  • Decreased risk of participation: for the patients enrolled, the trial decreases the risk that they will be allocated to a control group (which is smaller) or to an ineffective treatment (which would be dropped from the study). 
• Disadvantages:
  • Data complexity: the added care that is required to manage the responsive randomisation, multiple stages of interim analysis, multiple arms,  the design of a master protocol with longevity - all of these are extremely labour-intensive from a statistical  perspective
  • Administrative complexity: each intervention may have its own corporate sponsor, its own additional consent requirements, and follow-up might be different, making the process of running a platform trial more complex. 
  • No fixed end date: harder to secure funding
  • More difficult to togansie and plan: unsuited for interventions that need to be investigated immediately
  • Nonconcurrent control group could bias the results, for example where the standard of care changes over time

b) Examples from ICU literature are far fewer than the examples from oncology, where these trials are really popular. It is almost certain that most trainees would have put REMAP-CAP down for one of these, but there are a couple of others as well:

• REMAP-CAP
• ASCOT
• RECOVERY
• I-SPY COVID