Sonja Brajovic Medical Officer, Office of Surveillance and Epidemiology Center for Drug Evaluation and Research Food and Drug Administration

Transcription

1 FDA Perspective on MedDRA Coding Quality in Post marketing Safety Reports European Informal MedDRA User Group Webinar Sonja Brajovic Medical Officer, Office of Surveillance and Epidemiology Center for Drug Evaluation and Research Food and Drug Administration October 31, 2012 Disclaimer: The information within this presentation represents the views of fthe presenter, not necessarily those of the FDA or any other referenced organization. CDER Office of Surveillance and Epidemiology 2 1

2 Acknowledgements: Medical Dictionary for Regulatory Activities (MedDRA ) is the international medical terminology developed d under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). MedDRA is a registered trademark of the International Federation of Pharmaceutical Manufacturers Associations (IFPMA). CDER Office of Surveillance and Epidemiology 3 Topics MedDRA use at FDA CDER MedDRA use in the FDA Adverse Event Reporting System (FAERS) FDA Quality Control of manufacturersubmitted coding Missed codes Soft coding FDA Recommendations CDER Office of Surveillance and Epidemiology 4 2

3 Key Features of MedDRA An ICH standard, an international medical terminology used by regulatory authorities and biopharmaceutical industry in pre and post marketing, for data entry, retrieval, evaluation and presentation: MedDRA specificity enables medical accuracy in coding MedDRA hierarchy and Standardised MedDRA Queries (SMQs) allow for useful data retrieval and presentation Global ICH endorsed guides for both coding and data retrieval Global version synchronization Standardized communication of coded data Maintenance by the MedDRA Maintenance and Support Services Organization (MSSO) CDER Office of Surveillance and Epidemiology 5 Scope of MedDRA Diseases Diagnoses Signs, symptoms Therapeutic indications Investigation names & qualitative results Medical & surgical procedures Medical, social, family history Medication errors Product quality terms CDER Office of Surveillance and Epidemiology 6 3

4 ICH endorsed MedDRA Guides MedDRA Points to Consider documents MedDRA Term Selection MedDRA Data Retrieval and Presentation CDER Office of Surveillance and Epidemiology 7 ICH endorsed MedDRA Guides (2) Appendix: MedDRA versioning approach Versioning methodologies Recommendation for version implementation Date of New Reporting Version for Individual Case Safety Reporting A new release version of MedDRA should become the reporting version on the first Monday of the second month after it is released.for example : 1 March MedDRA X.0 released First Monday of May MedDRA X.0 becomes the reporting version 1 September MedDRA X.1 released First Monday of November MedDRA X.1 becomes the reporting version CDER Office of Surveillance and Epidemiology 8 4

5 MedDRA use in FDA Centers Center for Drug Evaluation and Research (CDER) uses MedDRA in pre and post marketing FDA Adverse Event Reporting System (FAERS) database, formerly AERS, uses MedDRA since 1997; legacy data migrated Center for Biologics Evaluation and Research (CBER) Vaccine Adverse Event Reporting System (VAERS) database, uses MedDRA since 2007; legacy data migrated Center for Food Safety and Applied Nutrition (CFSAN) CFSAN Adverse Event Reporting System (CAERS) database uses MedDRA since 2002 CDER Office of Surveillance and Epidemiology 9 Is MedDRA Required at FDA? FDA currently does not require MedDRA However, most drug reports from manufacturers are received electronically, pre coded in MedDRA In March 2003, FDA issued a proposed rule (Safety Reporting Requirements for Human Drug and Biological Products) to require MedDRA for coding of post marketing adverse event reports rule is not final CDER Office of Surveillance and Epidemiology 10 5

6 Use of MedDRA in CDER (1) In FAERS, MedDRA is used to code: The events adverse events medication errors product quality issues accompanied by adverse events Indications for use Our Data entry contractor (DSI International) has a coding staff Majority of manufacturer reports are submitted electronically pre coded in MedDRA Our coding staff performs QC on manufacturer coding CDER Office of Surveillance and Epidemiology 11 Use of MedDRA in CDER (2) Pre approval clinical trials Safety data submitted with new drug applications (NDA) are most often coded in MedDRA Medical officers and biostatisticians in CDER have increased their use of MedDRA in recent years CDER Office of Surveillance and Epidemiology 12 6

7 Safety in the Lifecycle of FDA regulated Products Post Marketing Safety Surveillance Preclinical Safety Phase 1 Phase 2 Phase 3 A p Safety Safety p Safety Dose Efficacy r Ranging o v a l Safety Concern Strategies and Actions to Minimize Risk CDER Office of Surveillance and Epidemiology 13 How post marketing adverse event reports get to FDA? Patients, consumer, and healthcare professionals voluntary voluntary FDA MedWatch Manufacturer FDA regulatory requirements FDA s Adverse Event Reporting System (AERS) database CDER Office of Surveillance and Epidemiology 14 7

8 Regulations and Laws for Post Marketing Reporting of Adverse Experiences 21 Code of Federal Regulations (CFR) Prescription drugs without Approved Application Drugs New Drug Application (NDA) Generic drugs Abbreviated NDA (ANDA) Biologics Biologics License Application (BLA) Section 760 of Food Drug and Cosmetic Act Non Rx drugs without approved application (mainly the monograph OTCs ) CDER Office of Surveillance and Epidemiology 15 Definitions Adverse drug experience. Any adverse event associated with the use of a drug in humans, whether ornotconsidereddrug drug related, including the following: An adverse event occurring in the course of the use of a drug product in professional practice; an adverse event occurring from drug overdose whether accidental or intentional; an adverse event occurring from drug abuse; an adverse event occurring from drug withdrawal; and any failure of expected pharmacological action Serious adverse drug experience. Any adverse drug experience occurring at any dose that results in any of the following outcomes: Death, a life threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect important medical events. Unexpected adverse drug experience. Any adverse drug experience that is not listed in the current labeling for the drug product. This includes events that may be symptomatically and pathophysiologically related to an event listed in the labeling, but differ from the event because of greater severity or specificity. CDER Office of Surveillance and Epidemiology 16 8

9 FAERS FDA's post marketing safety surveillance database for drug and therapeutic biologic products FDA uses FAERS data to monitor, identify and analyze adverse events and medication errors FDA staff in CDER and CBER regularly examine the FAERS database as part of routine safety monitoring When a potential signal of a serious risk is identified from FAERS data, it is further evaluated lance/adversedrugeffects/default.htm CDER Office of Surveillance and Epidemiology 17 Type of Reports in FAERS CDER: Drugs and therapeutic biologics, prescription + over the counter (OTC) products CBER: Tissue products, therapeutic blood products Paper submissions 3500 (voluntary) and 3500A (mandatory) forms Electronic submissions of mandatory ICSRs International ICH E2B(R2) standards ~6 million reports, data since 1969 Over 800,000 reports entered in 2011 CDER Office of Surveillance and Epidemiology 18 9

10 Qualities of a Good Case Report What makes a good case report? Description of the event Suspected product(s) and concomitant treatment details Patient characteristics, medical history, treatment history Documentation of the diagnosis Clinical course and outcomes Treatment and lab values at baseline, during therapy, and after therapy Response to dechallenge and rechallenge Any other relevant information Source: US FDA. Guidance for Industry. Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment. March 2005 CDER Office of Surveillance and Epidemiology 19 FAERS and MedDRA Coding Standards ICH Endorsed Guide for MedDRA Users: MedDRA Term Selection (MTS): Points to Consider (PTC) Designed to promote medical accuracy and consistency in term selection FDA Coding Principles for Postmarketing Adverse Event Reports are harmonized with the ICH MTS PTC document FDA encourages firms to base their own coding guidelines on, and not conflict with, the ICH MTS PTC document CDER Office of Surveillance and Epidemiology 20 10

11 Safety Signals What is a signal? Information suggesting a possible safety concern that needs further assessment Many potential sources: Adverse event and medication error reports (FAERS) Clinical trials Meta analyses of clinical trials Observational studies Medical literature Other sources (e.g., FDA s foreign counterparts) CDER Office of Surveillance and Epidemiology 21 Why FDA Evaluates Manufacturer submitted MedDRA Coding FDA depends on many different companies to submit accurate and complete MedDRA coded reports Rely on coded data to perform analyses and generate important safety signals Inaccurate and/or incomplete coding results in delayed, misdirected or missed safety concerns FDA notes inaccurate coding: missed concepts soft coding issues (selecting a term which is both less specific and less severe than the reported event, although an appropriate term exists in MedDRA) CDER Office of Surveillance and Epidemiology 22 11

12 Coding issue missed concept / soft coding Patient on Drug X, admitted for liver disorder (long, detailed narrative documents 40 days of hospitalization and treatment) Patient died from liver failure. Submitted as: LLT PT Liver disorder Expectation: LLT PT Hepatic failure CDER Office of Surveillance and Epidemiology 23 Coding issue missed concept Patient on Drug X, had cardiac arrest. Developed acute renal failure. Recovered after haemodialysis. Submitted as: LLT PT Cardiac arrest Expected: LLT PT Cardiac arrest AND LLT PT Renal failure acute CDER Office of Surveillance and Epidemiology 24 12

13 Coding issue missed concept Patient took drug X while pregnant, had a spontaneous abortion Submitted as: LLT Drug exposure during pregnancy PT Maternal exposure during pregnancy Expectation: LLT Drug exposure during pregnancy AND LLT PT Abortion spontaneous CDER Office of Surveillance and Epidemiology 25 Coding issue Missed concept Patient on drug X (note: drug prescribed only with two documented forms of birth control) ) became pregnant, delivered a normal baby Submitted as: LLT Normal birth PT Delivery or LLT Normal baby PT Normal newborn Expectation to also code for pregnancy, or for drug exposure during pregnancy: LLT Unintended pregnancy OR LLT Drug exposure during pregnancy AND LLT Normal baby CDER Office of Surveillance and Epidemiology 26 13

14 Coding issue Soft coding acute haemorrhagic pancreatitis Submitted as: LLT PT Pancreatitis acute Expectation: LLT PT Pancreatitis haemorrhagic CDER Office of Surveillance and Epidemiology 27 Coding issue Soft coding bloody pericardial effusion Submitted as: LLT PT Effusion Another manufacturer coded as: LLT PT Pericardial disease Expectation: LLT Effusion pericardial bloody PT Pericardial haemorrhage CDER Office of Surveillance and Epidemiology 28 14

15 Coding issue Soft coding Two days after Drug X, patient developed anuria... (long narrative, dtildl detailed labs, etc) t) Acute renal failure resolved. Submitted as LLT PT Anuria Expectation: LLT PT Renal failure acute CDER Office of Surveillance and Epidemiology 29 Coding issue Soft coding Two days after Drug X, patient had increased creatinine. The kidneys shut down, patient placed on dialysis. Submitted as LLT Creatinine increased PT Blood creatinine increased Expectation: LLT PT Renal lfailure (Optional to also add LLT PT Dialysis) CDER Office of Surveillance and Epidemiology 30 15

16 FDA MedDRA QC Evaluation Results Overall, coding is of good general quality When a coding issue is identified, FDA may: Review other similarly coded manufacturer reports Review larger sample of all coded manufacturer reports Discuss the identified coding issue(s) with the manufacturer Include review of a manufacturer s coding practices in an AE compliance inspection by FDA (either routine inspection or for cause inspection) 31 FDA Recommendations Firms should take advantage of MedDRA s specificity to avoid coding errors Critical for later retrieval / signal generation FDA encourages firms to follow ICH Endorsed Guide for MedDRA Users: MedDRA TERM SELECTION: POINTS TO CONSIDER Firms should establish their own coding guidelines based on, and not conflicting with, the ICH MTS:PTC document Internal Quality control processes to ensure medical accuracy, uniformity and consistency Training! CDER Office of Surveillance and Epidemiology 32 16

17 Acknowledgements FDA colleagues Toni Piazza Hepp Roger Goetsch Amarilys Vega CDER Office of Surveillance and Epidemiology 33 Thank you! Questions/discussion CDER Office of Surveillance and Epidemiology 34 17