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Editorials
Di
Bella's therapy:
the last word?
The
evidence would be stronger if the researchers had randomised their studies
The researchers, who were
funded by the Italian government, conducted 11 independent uncontrolled multicentre trials in which 386 patients
with different types of advanced cancer were given Di Bella's multitherapy. They found no evidence of a clinically important
response, and treatment was discontinued in 86% of the patients
because of disease progression, toxicity, or death. Most clinicians
will, we suspect, find this convincing evidence, but it is not
perfect. We don't know whether the patients enrolled into these
studies (all people who had asked for Di Bella's treatment)
were representative, and we don't know whether controls would have
done better or worse. The researchers should have conducted randomised
controlled trials.
Why were these trials not
randomised? Even though some experts claim that phase II clinical trials are
usually non-comparative,3 and the authors argued that they were using
these studies to assess whether randomised studies were warranted,2 the best way of avoiding bias is
through randomising patients to intervention and control groups.4 The usual reasons for
not randomising are difficulties with randomisation and recruitment,
cost, ethical considerations, and time.5
Difficulties with
randomisation or recruitment seem to be weak reasons. Most would agree that simultaneously
performing 11 multicentre studies
within 10 months is no mean feat. So why not take it a bit
further? The authors claim that patients would probably not have
agreed to be randomly allocated to different treatments (or, in this
case, placebo). But is that really so? Given that "several
thousand patients requested treatment with Di Bella's multitherapy," several hundred might well have agreed
to participate in a randomised controlled trial. Costs may have
played a part. Arguably it would have been better to assess Di Bella's therapy in
fewer types of cancer, but there was obviously a need to test the
treatment in a broad range of cancers. The authors also say that
they could not have done randomised trials for ethical reasons
but
these are not clear. Indeed, some would claim that the inferior design
of these studies was unethical. Time was probably the most influential
factor, as there was increasing public pressure on the Italian
health minister to clarify this issue.6
The design of these studies
is flawed; the results are already known; and Di Bella and his followers
probably would not accept the findings, even if the studies had been
randomised, double blind, and placebo controlled. So, why are we
publishing this paper in the BMJ? Firstly, even though the
results have appeared in the media, these studies and their design
have not been formally published. Secondly, we should acknowledge
this swift concerted action against a bogus therapy of nationwide
importance. Thirdly, treating this topic seriously may prevent
future casesboth of the implementation of
treatments with unknown efficacy and side effects and of studies of
weak design to answer important questions.
Marcus Müllner
BMJ
- Abbasi
K. Di Bella's cure
declared ineffective. BMJ 1998; 317: 366
[ Free Full Text].
- Italian Study Group for the Di Bella Multitherapy Trials. Evaluation of an unconventional
cancer treatment (the Di Bella Multitherapy):
results of phase II trials in Italy. BMJ 1999; 318: 224-228
[Abstract/Free Full Text] .
- Bellisant E, Benichou J, Chastang C. The group sequential triangular test for phase II cancer trials. Am J Clin Oncol 1996; 19: 422-430[Medline].
- Chalmers I. Unbiased, relevant,
and reliable assessments in health care. BMJ 1998; 317:
1167-1168
[Free Full Text] .
- Sibbald
B, Roland M. Understanding controlled trials. Why are randomised
controlled trials important? BMJ 1998; 316: 201
[Free Full Text] .
- Turone
F. Italy starts trials for controversial cancer treatmtent.
BMJ 1998; 316: 327
[Free Full Text] .
This article has been cited by other articles:
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Rapid Responses:
Read all Rapid Responses
Compared
to what?
J L Reyes
bmj.com, 21 Jan 1999 [Full text]
We
totally disagree with Müllner's view
R Raschetti
bmj.com, 8 Feb 1999 [Full text]
Missing
the forrest while looking at
the tree
Alessandro Liberati
bmj.com, 16 Feb 1999 [Full text]
Other related articles in BMJ:
Papers
Evaluation of an unconventional cancer treatment (the Di Bella multitherapy):
results of phase II trials in Italy.
Italian Study Group for the Di Bella Multitherapy Trials
BMJ 1999 318: 224-228.
MULTIMEDIA
Book: Di Bella: the Man, the Cure, a Hope
for All.
Abi Berger
BMJ 1999 318: 268.
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