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How much safety data should be collected in clinical trials of approved drugs.pptx

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How much safety data should be collected in clinical trials of approved drugs.pptx Powered By Docstoc
					How much safety data should be
  collected in clinical trials of
       approved drugs?
    Why do more trials on approved
              drugs?
• Phase III (premarket) trials
  – Generally not powered to detect less common
    adverse events due to smaller sample size and
    healthier subjects
  – Shorter follow up time limiting evaluation of late
    adverse events
Premarketing trials rarely powered to
 detect less common adverse events




                 Glasser et al. J Clin Pharmacol 2007;47:1074-1086
Importance of post-market safety data
     collection: Vioxx example




“The finding that naproxen therapy was associated with a lower
   rate of MI needs further confirmation in larger studies.”

                          Bombardier et al. N Engl J Med 2000; 343:1520-1528
Importance of post-market safety data
     collection: Vioxx example




  - Relativerisk of thrombotic event 1.92
  - Increased relative risk only became apparent after
  18 months of treatment



                            Bresalier et al. N Engl J Med 2005;352:1092-102.
 Post-marketing surveillance:
An alternative to clinical trials?
Example of post-market surveillance
reported adverse events: Dabigatran



“FDA is working to determine whether the reports of bleeding
in patients taking Pradaxa are occurring more commonly than
would be expected, based on observations in the large clinical
trial that supported the approval of Pradaxa.”
    Evidence of need for more post-
     marketing safety analysis trials
• New molecular entities approved by the FDA between
  1980 and 1999: dosage changes occurred in 21%; 79%
  were related to safety
• After marketing: 51% of drugs have label changes
  because of safety issues, 20% of drugs get a new black
  box warning, and 3% to 4% of drugs are ultimately
  withdrawn for safety reasons
• Suggest that a wider variety of dosages and diverse
  populations needs to be included in the premarketing
  phase, and/or additional studies should be requested
  and enforced in the post-marketing phase
                   Cross J et al. Pharmacoepidemiol Drug Saf. 2002;11:439-446.
                   Glasser et al. J Clin Pharmacol 2007;47:1074-1086
 What safety data should post-market
            trials collect?
• Common side effects that are not life-
  threatening likely to be picked up in
  premarketing trials
• Focus on serious adverse events and events
  requiring removal of the agent as more
  clinically relevant side effects
Thank You

				
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