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5 Ways to Optimize Trial Designs

February 4, 2020

5 Ways to Optimize Trial Designs

1 - Better Design

  • Every design choice will have some effect on the required sample size
  • Good designs are efficient and thus reduce sample size
  • Design decisions include - randomization level (Subject level Vs Cluster level etc)
    • Crossover vs parallel (Crossover design can be more efficient if chronic disease)
    • Choice of endpoint - closer endpoint is to actual measure the better 
    • Some unneeded simplifications increase costs - dictomisation, treating TTE as binary, recurrent events as TTE
    • Covariate Selection should be part of the study design and protocol

2 - Real World Evidence

  • Using RWE can help researchers determine a viable study length and frequency of study events when designing their trial
  • Enable researchers to assess site feasibility from previous data from site-specific clinical trials that were successful
  • Create Synthetic Control Arms and therefore allow all recruited patients to be in the active arm
  • Trial planners can assess and model protocols to reduce potential patient issues which lead to dropout, prior to commencing the trial

3 - Bayesian Assurance

  • Frequentists can gain greater insight and ideally make better decisions to complement their frequentist trial with Bayesian assurance
  • Take advantage of prior information and expert opinion
  • Bayesian (Power) Assurance - “True Probability of Success” very useful at financial & scientific Review boards.
  • Can help you formalize your sample size sensitivity analysis

4 - Adaptive Trials 

  • Adaptive Designs can lead to more efficient clinical trials
  • Group Sequential Design & Sample Size Re-estimation facilitates interim analyses where you can either stop for benefit or futility or increase your sample size if the effect size is promising
  • Other Adaptive areas include enrichment, seamless trials and dose finding
  • Adaptive Trials can reduce costs and risks and result in earlier decisions
  • Patients may also favour enrolling in adaptive trials because of the increased probability they will receive more effective treatment

5 - Master Protocols

  • The FDA guidelines describe two types of master protocol designs. 
    • The basket trial design tests a single oncology drug in various populations 
    • The umbrella trial design is used to evaluate multiple investigational oncology drugs in a single disease population
    • Ability to “bundle” treatments and garner economies of scale (reduce paperwork and duplication of activities)
    • From the perspective of the sites there can be a great reduction in overhead resulting in significant cost savings
    • Evaluate safety and efficacy of treatments in parallel instead of sequentially
    • Reduce patient exposure to control arms

Suggested Reading

A guest blog post from Quanticate-Logo.

An Introduction to Adaptive Clinical Trial Designs - Guest Blog by Quanticate

 

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