PMS (post marketing surveillance)

pms studies for phase 4 clinical trials

1. PMS (POST MARKETING Surveillance) Submitted To: Submitted By : Prof. Dr. Harish Dureja Sandeep ( P’ceutical Department M.Pharma M.D.U , Rohtak ) (DRA) Ist Sem. Roll no.:1854

2. INDEX Introduction History Benefits of PMS Sources of PMS Types of surveillance Method of surveillance Manufacturer PMS system References

3. PHASES OF CLINICAL TRIALS Phase 0 : micro dosing Phase I : First in man- Safety Phase II: First in Patient- Dose , dosage forms Phase III: Efficacy , ADRs Post-marketing Surveillance or Phase –IV : Evaluation of in the real clinical setting.

4. Introduction Post marketing surveillance refers to any means of obtaining information about a product after it has been approved for public use . Section 505(0)(3) authorizes FDA to require certain post marketing studies and clinical trials for prescription drugs approved under section 505(b) and biological product approved under section 351 . cont…

5. Post-marketing surveillance of drug therefore play an important role to discover an undesirable effect that might present at risk. It provide additional information on the benefit and risk of the drugs.

6. HISTORY In the 1960 at least two serious drugs reactions were observed in many patient . thalidomide causes limbs deformities (phocomelia). The PMA, senator Edward Kennedy (D-Mass.) suggested that a better system was need for monitoring the use and effects of prescription drug after they are marketed. As a result, the joint commission on Prescription Drugs Use was established in 1976,funded largely by the drug industry , with the mandate to design a post-marketing surveillance system to detect , quantify and describe the anticipated and unanticipated effects of marketed drugs. The delayed discovery of the adverse effects spurred effects to improve post-marketing surveillance.

7. POST-MARKETING SURVEILLANCE No fixed duration/Patient population Starts immediately after marketing Report all ADRs Help to detect Rare ADRs Drug interaction Also new uses for drugs[sometimes called Phase V]

8. Limitations of Premarketing Clinical Trials Size of the patient population studied Narrow population - often not providing sufficient data on special groups Narrow indications studied Short duration

9. Benefits of Post-marketing Monitoring : The ability to study the following: •Low frequency reactions (not identified in clinical trials) •High risk groups •Long-term effects •Drug-drug/food interactions •Increased severity and / or reporting frequency of known reactions

10. SOURCES OF PMS INFORMATION: The following may be considered as sources of information : Expert user groups Customer surveys Customer complaints and warranty claims Post CE-market clinical trials. Literature reviews The media

11. Types of Post-marketing Surveillance Spontaneous/voluntary reporting of cases National (FDA MedWatch) Local or Regional (Joint Commission Requirement) Scientific literature publications Postmarketing studies (voluntary or required) Observational studies (including automated healthcare databases) Randomized clinical trials Active surveillance Drug-Induced Liver Injury Network (DILIN) Sentinel initiative

12. Spontaneous Reports A communication from an individual (e.g. health care professional, consumer) to a company or regulatory authority Describes a suspected adverse event(s) Passive and voluntary reports

13. Factors Affecting Reporting Media attention Litigation (class action lawsuits) Nature of the adverse event Type of drug product and indication Length of time on market Extent and quality of manufacturer’s surveillance system Rx or OTC product status Reporting regulations

14. FDA Adverse Event Reporting System (FAERS) Computerized database Spontaneous reports Contains human drug and therapeutic biologic reports > 7 million reports since 1969

15. FAERS Strengths Includes all U.S. marketed products Includes all uses Includes broad patient populations: elderly, children, pregnant women, co-morbidities Simple, relatively inexpensive reporting system Especially good for events with a rare background rate cont….

16. Useful for events that occur shortly after exposure Detection of events not seen in clinical trials (“signal generation”) Identification of trends, possible risk factors, populations, and other clinically significant emerging safety concerns

17. Safety Signal Reported information on a possible causal relationship between an adverse event and a drug The relationship being previously unknown or incompletely documented Supported by multiple case reports New unlabeled adverse events An observed increase in a labeled event OR a greater severity or specificity New interactions Newly identified at-risk population

18. Use of Data Mining Mathematical tool identifies higher-than-expected frequency of product-event combinations Tool for hypothesis generation Supplements FAERS data review Does not replace expert clinical case review

19. Developing a Case Series Identify a well-documented case in FAERS, published literature, data mining, or other sources to identify a safety signal. Using our knowledge of the clinical course of the disease, formulate a case definition which may include both clinical features and laboratory findings, sometimes even demographic information if we believe the safety signal is for a specific population. Complete a thorough database search for additional cases.

20. Regulatory Actions Labeling changes – i.e. Warnings, Precautions, Adverse Reactions Pharmacovigilance activities - enhanced surveillance (e.g., expedited reporting), registry, epidemiology studies Risk Evaluation and Mitigation Strategy (REMS) Communication plan, restricted use Drug Safety Communication (DSC) Market withdrawal

21. METHODS OF SURVEILLANCE: Thus, four types of studies are generally used to identify drugs effects: 1. Controlled clinical trials, 2. Spontaneous or voluntary recording 3. Cohort studies 4. Case control studies

22. CONTROLLED CLINICAL TRIALS: To minimize bias through such method as randomization Directly monitor patients for the duration of studies. For evaluating a drug’s efficacy and safety. They are often costly.

23. SPONTANEOUS REPORTING: A communication from an individual (e.g: health care professional, consumer) to a company or regulatory authority . This describes a suspected adverse event(S) But the actual incidence of adverse drug reaction can not be determined through spontaneous reporting.

24. COHORT STUDIES: Studies follow a defined group of patient for a period of time. Patient are not randomly assigned CASE CONTROL STUDIES: Case control studies identify patient with the adverse effects to be studied, and compare them with the sample drawn from the same cohort that gave rise to cases.

25. MANUFACTURER PMS SYSTEM: These are some of the type of knowledge and feed back which can achieved from a PMS system. Detection of some manufacturing problems. Product quality improvement. Conformation (or otherwise) of risk analysis. Knowledge of long term performance/reliability and /or chronic complication.

26. Knowledge of performance in different user population. Feedback on indication of use. Feedback on instruction for use. Feedback on use with other devices. Feedback on customer satisfaction. Feedback on continuing market viability.

27. How to report to MedWatch

28. How to Report: Online(www.fda.gov/medwatch ) Download the form Mail Fax [phone] For questions about the form: 1–800–332–1088

29. References http:// www.fda.gov/Safety/MedWatch MedWatch Safety Alerts: http:// www.fda.gov/Safety/MedWatch/ucm287881.htm http ://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm082196.htm#QuarterlyReports FOOD AND DRUGS ADMINISTRATION , Supplementary reports to contracts and grants committee on Medicaid”, from the division of Drugs Experience, BUREAU OF DRUGS,1982, 10-32.

30. Thank Y ou