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Data Monitoring Committees

Data Monitoring Committees. What is it?. =DSMB, IDMC, DRB, etc. EMEA guideline, Jan 2006 A group of independent experts external to a study assessing the progress, safety data and, if needed, critical endpoints of a clinical trials. Power of DMC.

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Data Monitoring Committees

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  1. Data Monitoring Committees Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  2. What is it? • =DSMB, IDMC, DRB, etc. • EMEA guideline, Jan 2006 • A group of independent experts external to a study assessing the progress, safety data and, if needed, critical endpoints of a clinical trials Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  3. Power of DMC • Contain experts (clinicians) in the therapeutic area in addition to research generalists + statistician • Independent of sponsor • Can unblind and analyse ALL data • A DMC charter defines • Data to be looked at Recommendations to Sponsor on future conduct of the trial Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  4. Why DMCs? Early detection of…. • Harm to trial participants • Benefit for trial participants • Futility (non-superiority) Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  5. How? Planned interim analyses for • outcome variables: • Mortality • Morbidity • Effect / lack of effect • Safety parameters • SAEs – but not necessarily each and every one • clinically significant trends in AEs Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  6. What should be monitored by DMC? • Endpoints (mortality/morbidity) • Accuracy and timelines of incoming data • Study recruitment – adequate? • Protocol adherence Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  7. Which sort of studies? Not all trials need DMCs! • Any controlled trial that compare rates of mortality and major morbidity • Studies in emergency situations where informed consent is waivered (coma) • Studies in vulnerable populations (mental handicap, children) • Risk of severe side-effects are high (chemo) Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  8. Terms of reference and procedures (cioms VI) • Confidentiality + communication • Blinding /unblinding • Presence/absence of sponsor • Members should be independent of sponsor • NB: Rules (charter) for monitoring the study should be made before the study starts Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  9. Examples – US trial • Newborns w. respiratory failure: Treatment: New Old p-value Deaths: 0/9 4/10 0,09 Trial stopped Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  10. Subsequent trial - UK Treatment: New Old p-value Deaths: 30/93 54/92 0,0005 Ethics: individual vs. collective Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  11. Lundbeck examples • Drug indicated for ischaemic stroke – monitoring effect on lab values • Drug indicated for schizophrenia - Monitoring hepatic events Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  12. When to stop? • Single primary outcome • The more you look, the higher risk of false-positive result (type I error) (that new treatment is better) • Sequence of planned interim analyses • Pre-defined stopping rules based on p-values for treatment difference • I.e: STOP trial at nth analysis if p< x • Only DMC aware of interim results Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  13. Stopping at which p-value? (cont’d) • Premature stop: • Inadequate treatment may enter clinical practice • Insufficient evidence collected on effective treatments • DMC can only advise sponsor to stop Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  14. Summary • DMCs useful and required in i.e. high-mortality studies • Composed of qualified clinicians, research people, statistician • Need to be independent of sponsor • Predefined: what to monitor, when to monitor, stopping rules Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

  15. ¿QUESTIONS ? ? Ulla Lønberg – International Safety & Pharmacovigilance – H. Lundbeck A/S21-Feb-2007

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