Randomised controlled trials : the basics


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we need to understand the basics of RCTs. this talk may help in this

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Randomised controlled trials : the basics

  1. 1. Randomized controlled trials The Basics
  2. 2. Definition  RCT is a study in which a group of investigators study an intervention in a series of individuals who receive the intervention in a random order.  Intervention to be tested is called the experimental group
  3. 3.  The other group of participants is called the control group.  The control can be conventional practice, a placebo, or no intervention at all
  4. 4. Schema of a simple trial Eligible patients Rx group 1 Rx group 2 Randomize
  5. 5. Why Randomize?  We need to analyse groups at the end of the trial  To ensure that difference in groups is because of the Rx  For this you need comparable groups at the start of trial  Purpose of randomization is to make the treatment groups comparable
  6. 6. Value of randomization  it reduces the risk of serious imbalance in unknown but important factors that could influence the clinical course of the participants.
  7. 7. RCT  ‘the most powerful tool in modern clinical research “ – Prospective – Controlled – unbiased
  8. 8. What is wrong with non- randomized studies?  Two main types of studies, those with and those without concurrent control groups
  9. 9. Non-randomized studies II  Without concurrent controls  Case series studies  Historical controls  type of patient may change, due to eligibility criteria  environment changes  data quality often quite different between groups
  10. 10. Non-randomized studies III  Controlled non-randomized studies  Difficult to argue that one group is different from another but allocation is predictable, so bias can arise from selection of patients  Randomization must be unpredictable
  11. 11. Random allocation  all participants have the same chance of being assigned to each of the study groups  the purpose is to keep both groups as similar to each as possible at the start of the trial.
  12. 12. Is coin tossing OK?  OK for big trials  For small trials, such ‘simple randomization’ can lead to imbalance in group sizes
  13. 13. Example: trial with 30 patients  If 30 patients are in a trial randomized using coin tossing there is a 14% chance of 15:15 split  For 16:14 chance is 27%  ‘Worse’ than 20:10 is 10%  Why ‘worse’?  Because imbalance leads to loss of power
  14. 14. We need randomization  to be done properly  to ensure similar numbers in groups  To combine with stratification -in large trials- to ensure comparability
  15. 15. Pseudo-randomisation  Alternating record number  Date of birth  Geographical distribution
  16. 16. True randomization  Need to separate the person who generates allocation from those who assess eligibility  Third party schemes  Telephone randomization service  Pharmacy randomization  Web-based service?  Envelopes  Sealed envelopes (preferably opaque)
  17. 17. Blinding  The best way to protect a trial against bias is by keeping the people involved in the trial unaware of the identity of the interventions for as long as possible
  18. 18. Types of RCTs  RCTs according to whether the investigators and participants know which intervention is being assessed – Open trials – Single blind trials – Double blind trials – Triple blind trials
  19. 19. Blinding is difficult  Having placebo in the same shape , formula and taste is very costly, and time consuming.  The drug side effects e.g. local reaction at the site of injection would partially unblind .  Impossible if surgical and medical treatments are compared.  The need for urgent unblinding code in case of serious side effects
  20. 20. Other types of RCTs  RCTs according to how the participants are exposed to the interventions – Parallel trials – Crossover trials  Trials testing one variable or factorial design e.g (2 X2 X 2)
  21. 21. Follow up  During the trial – Adherence to the study protocol – Patients compliance with treatment  After finishing the intervention, follow up of participants should be sufficiently long and complete
  22. 22. Analysis of clinical trials Analysis of clinical trials Intension to treat analysis Per treatment analysis Sub group analysis
  23. 23. Disadvantages of RCTs  expensive: time and money;  volunteer bias;  ethically problematic at times.
  24. 24. Interim Analysis  Done in large RCTs  To explore the results after recruiting of half of the participants  If marked difference is recognized , then trial should be stopped  Examples: WHI trial Breech Trial
  25. 25. So, how to do RCT  Set up a protocol  Recruit your patients  Randomize (try to be blind)  Follow up  Analyze your data  Publish
  26. 26. RCTs The gold standard for therapeutic research Basis for Meta-analysis Search for it first