Phlogenzym in the treatment of monoarticular gonarthritis

Klein G., Singer F., Herrera E.G.

December 2, 1998

A meta-analysis of three studies comparing efficacy and tolerance of Phlogenzym with that of Diclofenac in patients with monoarticular gonarthritis

Study 1: Phlogenzym in the treatment of a monoarticular gonarthritis, Principal Investigator: Prof. Gert Klein, Report: September 1997
Study 2: Phlogenzym in the treatment of a monoarticular gonarthritis, Principal Investigator: Un. Doz. Franz Singer, Report: July 1997
Study 3: Phlogenzym in the treatment of a monoarticular painful gonarthritis, Principal Investigator: Dr. Ernesto Garcia Herrera, Report: February 1998

Introduction

The sponsor company Mucos Pharma GmbH & Co., Geretsried, Germany, has performed three similar studies for comparing the efficacy and tolerability of Phlogenzym with that of Diclofenac in the treatment of patients with monoarticular gonarthritis. All studies were double-blind randomized controlled trials, with the same design: 3 weeks treatment with Phlogenzym or Diclofenac with observations at the beginning and at weekly intervals. Subsequently there were 4 weeks without treatment and after that there was a final visit.
Meanwhile all studies have been completed and three clinical study reports are available. The study reports have, however, some inherent shortcomings:

  1. The sample size of each study is rather small even if the outcome of the study is favourable for the alternative research hypothesis, i.e. favourable for the test drug.
  2. Although the protocol of the first study specified the point in time after three weeks of treatment as the primary comparison time, an amendment to this study protocol and the other two protocols stated that the primary comparison should be performed 4 weeks after cessation of drug treatment. This seems to be a rather unfortunate choice, as patients without treatment could (and did) dropout and it is not clear whether a comparison of untreated patients could be the base of the study objective, namely to deliver a statistical proof for therapeutic equivalence.

Otherwise these three studies were planned according to the requirements of the new Guidelines (e.g. ICH-Biostatistics Guideline E9). The trials were conducted in an acceptable fashion with the complete data base and all additional information available at the sponsor's site.