Use of a Data Mining Algorithm in Retrospective Analysis of Adverse Events of Withdrawn Marketed Drug Product - troglitazone (Rezulin)

Use of a Data Mining Algorithm in Retrospective Analysis of Adverse Events of Withdrawn Marketed Drug Product - troglitazone (Rezulin)

By Dr. Jacinta Aniagolu-Johnson

Objective:

The objective of this paper is to illustrate the use of the MGPS algorithm through a retrospective analysis of the post-marketing data contained in the AERS database for a set of a withdrawn drug product - troglitazone (Rezulin).

Background: To study the performance of MGPS in a real-world setting, the MGPS algorithm was applied retrospectively to the AERS database to generate signal scores (EBGM/EB05/EB95) for troglitazone that was approved treatment of type 2 diabetes mellitus in March 1997. Rare cases of reversible jaundice were reported in the controlled clinical trials that supported approval, but by October 1997, 35 cases of idiosyncratic hepatocellular injury (including 1 transplant and 1 death) had been reported to the FDA.

Methods: Using the MGPS algorithm, a two dimensional analysis was performed in a cleaned, de-duplicated and public release version of the FDA AERS database (through 4Q02) based on the following specifications: MedDRA PT-coded events; stratification by gender and age; sub-setting by FDA year (year reports were received by FDA); cumulative and discrete datasets by FDA receipt year; threshold minimum: EBGM 05 of > 1.0 for assessment; and drug search criteria by key ingredient or generic name

Results: For the event term hepatic failure, an EB05 of > 2.0 was determined and maintained from 1998 (post-drug approval year) to withdrawal year (2000) and post-approval years (2001 and 2002); year of exception was 1997. For the event term hepatocellular damage, an EB05 of > 2.0 was determined and maintained from 1997 (drug approval year) to withdrawal year (2000) and post-approval years (2001 and 2002).

Conclusions: Overall, by specific FDA year(s) a statistical significant EB05 (> 2.0) was determined for the specified MedDRA PT search terms for which the drug products were withdrawn from the market. EB05 statistical significance of >2.0 was reached and sustained (over the FDA years of post-approval marketing), either earlier or at the same time that a regulatory action (LC/DDL) was taken.

The same pattern was determined for specific event terms including ALT Increased and Blood Bilirubin Increased, expect that post-withdrawal year (in 2002) an EB05 of < 2.0 was determined for both event terms. A similar trend was determined for the cumulative analysis.

During the approval year (1997) 5 LCs and 2 DDLs were implemented and in addition, the FDA issued a Talk Paper. In both 1998 and 1999, additional LC and DDL were implemented and subsequently in 2000, the drug was withdrawn from the market.

POST COMMENT

Undeveloped gold in the single market status Article Marketing Key Guideline: Why You Should Do Article Marketing? Affiliate Marketing Holds Great Potential For Retailers And Publishers Alike Moles warts and skin tags removal Scam or Any Legit? Tips to write a sales copy to convince target market about your product Master Cleanse Secrets Review - Legit or Scam? Master Cleanse Secrets Scam or Any Legit? Xtreme Profit Robot Review - Another Scam Product? Finding a Niche for Online Marketing Hair Salon Software: Good Tool for Marketing Fibroids Miracle Scam or Any Legit? Tony Morrison My Airfare Secrets-My Airfare Secrets Scam Muscle Gaining Secrets Scam-Muscle Gaining Secrets Review