CLINICAL DATA GAP BETWEEN PHASE III CLINICAL TRIALS (PRE-MARKETING) AND PHASE IV (POST-MARKETING) STUDIES: EVALUATION OF ETANERCEPT IN RHEUMATOID ARTHRITIS

Main Article Content

Pendar Farahani
Mitchell Levine
Kathryn Gaebel
Lehana Thabane

Keywords

Rheumatoid Arthritis, etanercept, post-marketing study, comparative study

Abstract

Background


There are fundamental differences in design between phase III clinical trials and phase IV post-marketing studies that involve patient characteristics, the clinical setting (environment) and the manner of drug use. As well, many phase IV studies are extensions of randomized clinical trials (RCTs) and suffer from selection bias.


 Objective


To determine if the data obtained from RCTs of etanercept (Enbrel®) in the treatment of rheumatoid arthritis would be representative of the effects attainable in community practice.


 Method


An analysis was conducted comparing data from published RCTs of etanercept use in rheumatoid arthritis patients with data collected in a community based cohort study that was not an extension of an RCT.


 Results


Baseline clinical  data, such as  tender or  painful joint count, patient’s global assessment, the heath assessment  questionnaire, physical  and  mental  component  summary  of  the  SF-36,  and  rheumatoid arthritis drug profile were significantly different between the patients receiving etanercept in the phase IV community cohort study and the patients enrolled in the RCTs. Differences in the baseline data for the control patients were also noted amongst the RCT studies. The treatment outcome, American College of Rheumatology (ACR) response rate of 20%, 50% and 70% at 6 month, was the same between the cohort study and the RCTs, but at 12 months the clinical response was less for the community based patients than for the RCT patients. At 6  months there were fewer withdrawals involving community-based patients than RCT patients due to less frequent withdrawals associated with lack of efficacy. At 12 months the withdrawal rate due to either a lack of efficacy or from adverse events was similar between data sets.


 Conclusion


The  data  from the  etanercept phase III  RCTs  may  not  reflect  the  characteristics of  patients using etanercept in community practice, nor the clinical outcomes observed by RA patients at 12 months. These discrepancies may be derived from methodological differences in study design and patient selection. On the other hand, outcomes such as withdrawal rates at 12 months appear comparable between the two types of populations.


 

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