Phlogenzym in the treatment of monoarticular gonarthritis. A meta-analysis of three studies comparing efficacy and tolerance of Phlogenzym with that of Diclofenac in patients with monoarticular gonarthritis.
Klein G., Singer F., Herrera E.G.
December 2, 1998
Study 1: Phlogenzym in the treatment of a monoarticular
gonarthritis. Principal Investigator: Prof. Gert Klein, Report:
September 1997.
MU-696 401.
Study 2:
Phlogenzym in the treatment of a monoarticular gonarthritis.
Principal Investigator: Un. Doz. Franz Singer, Report: July 1997.
MU-695 414.
Study 3: Phlogenzym in the treatment of a monoarticular painful
gonarthritis. Principal Investigator: Dr. Ernesto Garcia Herrera,
Report: February 1998.
MU-696 416.
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:
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.
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.