SAE Causality & Assessment and Compensation Issues

Transcription

1 SAE Causality & Assessment and Compensation Issues Dr. Y. K. Gupta Professor and Head, Department of Pharmacology All India Institute of Medical Sciences New Delhi, India

2 SAE assessment and reporting

3 GSR No 53(E) dt 30 Jan 2013 Trial related injury: Adverse effect of inv product Protocol violation, scientific misconduct, negligence by sponsor or investigator!!!! Failure of investigational product to provide intended therapeutic effect, in case the standard care, though available, was not to be provided to the subject as per the clinical trial protocol Use of placebo, in case the standard care, though available, was not to be provided to the subject as per the clinical trial protocol ADR due to concomitant medication Injury to child in utero Any trial related procedure 3

4 How to establish relatedness?? Causality Assessment: The evaluation of the likelihood that a medicine was the causative agent of an observed adverse event

5 Causality Assessment contd Adverse effects are rarely specific for a drug Diagnostic tests are usually absent Rechallenge is rarely ethical Structured and harmonised assessment of causality Precise, uniform and reliable quantitative estimation of relationship likelihood

6 Criteria for assessment Risk factors Challenge Dechallenge (outcome) Rechallenge (outcome) Possible alternative etiological causes Drug level

7 Criteria for assessment Nature (characteristics / mechanism) of the reaction Temporal relationship Previous reports on reported reaction Previous exposure to the drug Lab evidence

8 Methods for assessment Expert opinion Algorithms Probabilistic approaches

9 WHO scale Certain Probable Possible Unlikely Conditional/ Unclassified Unassessable/ unclassifiable

10 Naranjo s scale Questionnaire with 10 questions Answered Yes / No / Unknown Scores range from -1 to +2 Definite ( 9) Probable (5 8) Possible (1 4) Unlikely ( 0)

11 Causality assessment in clinical trials Certain Probable Possible Unlikely Related Not Related 1/23/

12 What if SAE is related Financial compensation for death Financial compensation and free management in case of injuries

13 Compensation issues

14 Guidelines on compensation Declaration of Helsinki The protocol should include information regarding.. provisions for treating and/or compensating subjects who are harmed as a consequence of participation in the research study. ICH GCP Guideline Para 5.8: Compensation to subjects and investigators Para : Written and other information to be given to participants. Indian GCP guidelines Para Compensation for Participation Para Compensation for Accidental Injury

15 Payment to research participants Free treatment of research related injury/reimbursement of such expenses Reimbursement of research related expenses Compensation for research related injury or death??????????????????

16 GSR No 53(E) dt 30 Jan 2013 Insertion of Rule 122 DAB: Compensation in case of injury or death during Clinical trial Injury to the trial subject Free medical management as long as required Trial related injury Medical cost + compensation Trial related death: Compensation to nominee Cost of compensation to be borne by sponsor 16

17 Compensation: Types Tort liability: seeker has to prove fault in court of law No fault

18 What? When? Who? How? And Whom? Of SAE Reporting Who to Whom? When? How? Investigator Sponsor EC Investigator Sponsor EC Appendix XI format DCGI, EC, Head of Institution, Sponsor DCGI, EC, Head of Institution DCGI [Chairman of Exp. Committee For death case] Initial: <24hrs Full report: within 10 calenda r days 10 calenda r days 21 calenda r days 1/23/

19 New SAE Reporting Process Patient / Relative SAE occurrence Initial Report Final Compensation to be paid Sponsor Sponsor Investigator Sponsor Chairman of EC DCGI Order of Compensation DCGI Analyzed Report *Chairman of Expert Committee DCGI Analyzed Report & Compensation Recommendatio n Investigator Sponsor Chairman of Ethics Committee DCGI *Chairman of Expert Committee Chairman of Ethics Committee 1/23/2016 * In case of Death 19 Sponsor

20 Quantum of compensation Gender Profession Income Age Dependants Concomitant medication Negligence Comorbid conditions Sponsor: Industry V/s Academia Expected survival How do you comprehend this?

21 Quantum of compensation - Factors No- fault basis Age factor: from The Workmen Compensation Act Risk factor: Subjective Base amount: Contemporary and dynamic

22 Quantum of compensation - Factors Two factors: Age factor Risk factor Risk Factor Patient Risk Base amount: Rs 80.5lacs Terminally ill (survival NMT 6 months) 1 High risk (survival NMT 6 24 months) 2 Moderate risk 3 Mild risk 4 Healthy volunteers; No risk 22

23 Quantum of compensation - Formula Compensation = (8 lacs *Age factor*risk factor)/99.37 Compensation for terminally ill patient of 16 yrs of age: (8 X X 0.5)/99.37 = Approx 9 lacs Compensation for terminally ill patient of 67 yrs of age: (8 X X 0.5)/99.37 = 4 lacs Expected mortality > 90% in 30 days Fixed amount of 2 lacs 23

24 To simplify Age Risk factor Compensation >65 yrs 4 32 Lacs < 16 yrs Lacs >65 yrs Lacs < 16 yrs Lacs

25 Compensation for injuries A permanent disability Compensation = (DX80XC)/(100X100) Congenital anomaly or birth defect Still birth b) Early death due to anomaly c) No death but deformity which can be fully corrected through appropriate intervention d) Permanent disability (mental or physical) Chronic life-threatening disease Compensation = N x W Reversible SAE in case it is resolved Compensation = 2 x N xw 1/23/

26 Emerging Issues Compensation in Investigator initiated trials? Accreditation of trial sites, ECs and investigators Interpreting foreign trial data for regulatory decisions Compensation on compassionate grounds? 1/23/

27 Thank You