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Statement from the Treatment Action Campaign of South
Africa
MCC Decision to Deregister Nevirapine for Mother-to-Child
Transmission Prevention
is Disturbing and Confusing
31 July 2003The Medicines Control Council (MCC) is one of
the most important institutions in public health. Its only task is to
ensure the safety, efficacy and quality of medicines in the public interest.
An independent and fearless MCC is essential to the health care system.
In 1996, the MCC registered nevirapine, an anti-retroviral for the daily
treatment of HIV/AIDS. This registration was done in accordance with its
statutory mandate. In April 2001, the MCC also registered nevirapine to
reduce mother-to-child HIV transmission.
Regrettably, the MCC has played political games with the registration
of nevirapine for mother-to-child-HIV transmission since November 1999.
Unfortunately, the MCC's questioning of science appears to coincide with
the conversion of President Mbeki and Minister Tshabalala-Msimang to HIV
denialist science. Despite their protestations, the MCC cannot deny the
enormous political pressure brought to play on it during the registration
process and in the MTCT court case.
Now, the MCC has rejected the Ugandan HIVNET 012 study on the prevention
of mother-to-child HIV transmission. It has stated that it will deregister
nevirapine for single-dose mother-to-child transmission prevention (MTCTP)
in 90days unless the patent-holder supplies it with new data.
Many thousands of pregnant women and communities have already been confused
by the forays of the MCC into the politics of medicines and anti-retrovirals.
HIV/AIDS denialists misuse the MCC's authority to cause further confusion
and harm in our communities. The MCC has not provided the public with
any new scientific information to support it's inexplicable position.
The recent work of the MCC to register generic ARVs including nevirapine
is being undermined by its fork-tongued approach.
Nurses and doctors in public hospitals and clinics around South Africa
have expressed dismay at this decision because it undermines the sustainability
of the public sector MTCTP programme. This programme has the potential
when it is fully rolled out to prevent approximately 30,000 babies from
contracting HIV every year.
Nevirapine is not the only drug that can be used to reduce mother-to-child
HIV transmission. AZT and other anti-retrovirals can be used as individual
drugs or in combination for this purpose. Since its inception TAC has
campaigned for the use of AZT. This is slightly more expensive and complex
that nevirapine. But, it is also more effective.
The TAC has for a long time called for hospitals and clinics, where capacity
exists, to begin using more effective regimens than short-course nevirapine,
but the reality is that many facilities will not be in a position to upgrade
their programmes to better regimens for months or even years to come.
It is these facilities whose MTCTP programmes will be endangered if the
MCC carries out its threat.
The MCC's position contradicts a press statement by the World Health Organisation
(WHO) released in July 2003 (see attached)
which states that short-course nevirapine for MTCTP should be part of
the minimum standard of care for HIV-positive women and their children.
Nevirapine can be used and is used in the United States, contrary to a
popularly upheld belief frequently propagated by AIDS denialists. Short-course
nevirapine is recommended by the US Public Health Service Task Force for
MTCTP among HIV-positive women in labour who have had no prior therapy.
It is also included on the WHO essential medicines list for both treatment
and prevention purposes.The TAC rejects this confusing and seemingly unjustified
decision by the MCC without a clear public explanation of its reasons
or motives. If there is evidence that it has acted either incompetently
or under political influence, there will be a dangerous loss in confidence
by the public, but especially health care workers, in South Africa's medicines
registration system. All the publicly available data on short-course nevirapine
used for mother-to-child transmission prevention indicates that it is
safe and effective.
If the MCC has information to the contrary, it must make
this available because of the public interest in this issue. In the meanwhile
the TAC will seek legal opinion from its lawyers on how to proceed on
this matter
Evidence for the Efficacy of Short-Course Nevirapine
In a radio interview on Cape Talk (30 July 2003, 21:00-22:15 - transcript
will be made available next week) the MCC chairperson, Professor Peter
Eagles, stated unequivocally that that the MCC's decision is based on
its concerns over the efficacy of short-course Nevirapine and not its
safety. The MCC is aware of the following evidence that supports the efficacy
of short-course Nevirapine:
a. The HIVNET 012 trail conducted in Uganda found that short-course nevirapine
reduced transmission by nearly half.
b. The South African Intrapartum Nevirapine Trail (SAINT) has confirmed
that short-course nevirapine (albeit with two doses to the mother, instead
of one as used in Uganda) is effective.
c. A number of trials have been (or still are being) conducted using short-course
nevirapine added to other MTCTP regimens. These trials have demonstrated
added efficacy due to the addition of short-course nevirapine to other
standard regimens. One of these studies combined short-course AZT with
short-course nevirapine and found that AZT plus nevirapine reduced transmission
by about 50% over AZT alone. The Western Cape Department of Health has
indicated that it intends to switch to this regimen.
d. A study conducted at a hospital in South Africa that has been submitted
for publication examined 300 babies on a short-course nevirapine mtctp
programme (women were encouraged to use formula milk as well). The study
found a transmission rate of just under 9% at three months. This is much
lower than the typically seen 25 to 35% transmission rates in the absence
of MTCTP. This study confirms the operational effectiveness of short-course
nevirapine. (Researchers have requested confidentiality until the study
is published, but the MCC is aware of their findings.)
e. A nevirapine MTCTP programme in Lusaka, Zambia found a transmission
rate at 6 weeks of slightly over 11%. This study also confirms the operational
effectiveness of short-course nevirapine.
f. An unpublished study from a hospital in Uganda implementing short-course
nevirapine found a transmission rate of about 12%. Before the programme
this hospital recorded a rate at 6 weeks of 20%.
The above demonstrates unequivocally that the available evidence indicates
that short-course nevirapine is effective for MTCTP.The MCC's ConcernsHIVNET
012
In the above-mentioned radio interview, Professor Eagles stated that the
MCC is unsatisfied with the conduct of the HIVNET 012 trial in Uganda
and therefore no longer considers this evidence of the efficacy of short-course
nevirapine. The facts however are as follows:
a. The MCC registered short-course nevirapine for MTCTP
without expressing any concerns about the documentation from the HIVNET
012 trial in 2001.
b. The US based Food and Drug Administration (FDA), which is the MCC's
equivalent body in the US, returned an application for registration for
short-course MTCTP to the patent-holder because the HIVNET 012 trial's
documentation was not kept (nor ever intended to be kept) at the standards
required by the FDA. The FDA arguably has the most arduous documentation
requirements of any medicine regulatory authority in the world. The MCC
does not have the same documentation requirements and registers many medicines
that the FDA does not. This is a rational attitude in a country like South
Africa which has a less litiguous environment than the US and significantly
worse health issues. Nevertheless, the MCC has a justified reputation
for requiring high-standard documentation. Surely, we must assume that
the MCC was satisfied with the documentation supplied to it regarding
the HIVNET 012 trial before it registered short-course nevirapine for
MTCTP.
c. The National Institutes of Health who conducted the HIVNET 012 trial,
commissioned an independent audit of the trial to address concerns raised
about the documentation and conduct of the trial. This audit found that
although there were some irregularities in the documentation (which is
common in many trials), nothing they found cast doubt on the findings
of the safety and efficacy of nevirapine. The criticisms of the audit
related to standards of patient consent and unreported adverse events
unrelated to nevirapine (such as malaria and one child being born with
an extra digit). Professor Eagles stated that it is on the basis of this
audit's findings that the MCC has made its decision not to consider HIVNET
012 as evidence of the efficacy of short-course nevirapine. Yet, the MCC's
decision contradicts the finding of the audit. If anything the audit has
added to the confidence we can have in the HIVNET 012 trial.
d. In the radio interview, Professor Eagles first used the FDA's decision
not to register short-course nevirapine to justify the MCC's decision.
It was then pointed out to him that the MCC registers many medicines that
the FDA does not register. He denied this. But when specific examples
of such medicines were pointed out to him, he began arguing that the MCC
is an independent body that does not take its cue from the FDA. Surely
Professor Eagles cannot have it both ways unless rational argument is
to be suspended. As it happens, we concur with his view that the MCC most
certainly should be an independent body and that although it should consider
FDA opinion, it should not base decisions primarily on FDA concerns about
documentation requirements.
SAINT
The MCC has also cast doubt in the past on the findings of SAINT (see
the affidavit by Jonathan Levin of the MCC in the MTCTP court case on
the TAC website). It argued that SAINT was setup to demonstrate the superiority
of nevirapine over short-course AZT/Lamivudine. The trial failed to establish
this and since it was not set up as an equivalence trial, its findings
on the efficacy of short-course nevirapine cannot be inferred.
This is an unduly picky argument which fails to consider that the slightly
better efficacy of the AZT/Lamivudine arm was not considered statistically
significant, but more importantly that the nevirapine results (12.3%)
were far better than placebo results from other trials (such as PETRA)
and data on transmission rates where no intervention has taken place.
Even in Levin's affidavit (and when he gave testimony at a parliamentary
hearing on this issue) he acknowledges that short-course nevirapine is
effective. His argument is merely that it is not as effective as found
in the HIVNET 012 trial.
TAC members learnt from scientists and lawyers that the MCC should take
into account all available evidence and that it is not obliged to consider
only the findings of trials in isolation from each other. It should also
consider operational experience and comparisons of results between trials.
Frequently the MCC makes decisions doing just this and frequently the
MCC is alerted to flaws in trials, but yet accepts their overall results
on the balance of evidence. Clearly, given the available evidence, it
is not doing so here. It actually seems to be doing the opposite: trying
to find ways to cast doubt on the findings of essentially well-conducted
scientific trials.
Professor Eagles's Contradictions
In the Cape Talk interview, Professor Eagles denied that the WHO had issued
a statement directly supporting short-course nevirapine, but the WHO statement
(see below) was read out to him over the air. Professor Eagles contradiction
regarding the FDA has already been pointed out. Furthermore the following
package insert was read out to Professor Eagles from a registered flu
relief medicine package insert:
"Vitamin C (ascorbic acid) has been claimed to be an essential factor
in building up the patients resistance to infections as well as speeding
their recovery rate."
It is clear then that the MCC allows package inserts to indicate claims
where there is some evidence, even if that evidence is not overwhelming.
We argue that the available evidence that short-course nevirapine is effective
is overwhelming. If the MCC has some doubts over nevirapine's efficacy,
surely it must allow manufacturers of the medicine to state that the balance
of evidence demonstrates that nevirapine is effective for the purposes
of mother-to-child transmission prevention. Professor Eagles offered no
adequate response to this argument.
We will make the transcript of this interview available once we have obtained
the tapes from Cape Talk.MCC Must Re-establish Public and Health-Care
Worker Confidence
The MCC's decision has caused a crisis of confidence in its competence
and independence. It can however take steps to rectify this. Either it
must produce convincing evidence that most of the data supporting the
effectiveness of short-course nevirapine is significantly flawed or it
must retract its decision to deregister short-course nevirapine for MTCTP
in 90 days unless the patent-holder produces more evidence of the medicine's
effectiveness. The TAC would welcome either of these two routes. Furthermore,
we believe that the irrational views on HIV purveyed by the Minister of
Health, has demonstrated the need for a review of the current legislation
whereby the Registrar of Medicines is appointed (and can be removed) by
the Minister of Health.
Short-course nevirapine is by no means the best way to conduct MTCTP,
but it has offered hope to hundreds of thousands of mothers, nurses and
doctors. It would be scandolous if this hope is eroded by unscientific,
politically influenced decisions.
[END OF TAC STATEMENT]
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