Tuesday 25 September 2007

When Bad Science costs lives





Exposing bad science, quackery, pill-peddling and the like isn't just fun, it's an important part of ensuring that rational thought and evidence-based policy prevails over all forms of woo.




Nonetheless, every so often the rejection of scientific rigour becomes more than a matter of promoting sugar pills as a cure for the common cold. Every so often ignoring science in favour of wishful thinking actually costs lives. And we're not even talking about promoting Vitamin C as an alternative (superior alternative, no less) to AZT anti-retroviral treatment, dangerous thought that is. No, this goes deeper than that.





Welcome to Virodene.




According to some first-rate investigative journalism you can (nay, should) read here (which is a shameful redirect from Ben Goldacre's MiniBlog) in January 1997, Thabo Mbeki's ANC entertained a presentation on a novel approach to treat patients with AIDS. AIDS, lest we forget, was and is ravaging South Africa's population. The presentation was given by researchers who claimed to have developed an effective anti-HIV treatment, and claimed that


"[Virodene P058]"destroyed the virus in a test tube"; when given to humans
"appeared to reverse full blown AIDS to HIV positive"; fought "HIV in areas
other drugs cannot reach it, such as in the lymph glands and the brain"; had
"minimal side effects"

Naturally, Mbeki and his associates were impressed - they were looking at saving millions of dollars and millions of lives, who wouldn't be? But the story darkens...



In most countries, procedure dictates that any novel drug treatment must be approved for human use by an independent authority, usually recognisable by their acronyms (the MHRA in the UK,the FDA in the USA, the YMCA in... sorry, this is not the time to be facile). In South Africa, the relevant authority is the Medicines Control Council (MCC). Did Virodene's manufacturers have the appropriate approval? Err, no, not according to the then chief of the MCC, Prof. Peter Folb, nor according to a subsequent enquiry into the researchers' conduct carried out by the University of Pretoria, as highlighted at the time by the British Medical Journal, no less. Indeed, not only was approval not obtained,before Mbeki's cabinet heard about the results from this "trial," the MCC hadn't even known that patients had recieved Virodene, nor indeed what Virodene was. Immediate suspension of the trial followed, with no further patients to receive the drug, which was administered in the form of a sub-dermal slow-release patch. In the absence of official approval for the drug implant, how did the small-scale patient trial get off the ground? With the implicit support and permission of the Minister of Health, Nkosazana Zuma is how.




Following the MCC's decision to suspend the administration of Virodene, the researchers, headed by husband and wife combination Zigi and Olga Visser, submitted several altered versions of their trial protocol to the MCC, all of which were rejected. Meanwhile, the Vissers lobbied both Health Minister Zuma and Mbeki for support, to the extent that Mbeki intervened to ensure that research into Virodene could continue, despite a previous Pretoria High Court judgment banning dispensation of Virodene for any purpose. Just to make the point clear here - the Prime Minister knew about, and was directly involved in, the unapproved and illegal use of Virodene, a drug for which no reliable toxiological or efficacy data were available.



Throughout the following months, political pressure was applied to the Medicines Control Council, with the ruling ANC party being dragged into a partisan showdown over Virodene by the opposition Democratic Party. The ANC appealed to

"the MCC to expedite the process that will allow for clinical tests to be
conducted on Virodene to determine once and for all the efficacy of the drug
against the AIDS epidemic."




This political pressure - applied, lest we forget, in the absolute absence of any reliable data suggesting Virodene actually had any anti-viral properties that could combat HIV - was ramped up, with senior ANC figures questioning the MCC's impartiality and independence from the pharmaceutical industry. Bear in mind here the heavy political gain to be made from a potential home-grown, cheap AIDS treatment that surpassed a Big Pharma treatment. This pressure resulted in a coup d'etat at the MCC, with all senior officials being replaced by close political allies of Mbeki and Zuma. Perhaps not the worst thing, however, as the new MCC comprehesively dismissed Virodene following an audit of all available in vitro data, throwing out the case for a clinical trial for the fifth time.



This should have ended the clamour for provision of Virodene, either in a full-vlown clinical trial, or as a so-called 'mercy treatment' to those with nothing to lose, but that was far from what happened.



Murky financial dealings aside, which appear to involve the ANC indirectly bailing out Virodene's manufacturers, Mbeki's government continued to ignore accepted scientific procedure when it came to AIDS treatments. Mbeki's opposition to AZT (azidothymidine, made by Glaxo Wellcome) is well-publicised. It is, however, always placed in the context of "HIV denialism," whereby supporters of this position claim not to believe that HIV causes AIDS, and that anti-retroviral drugs are not necessary to cure AIDS. Indeed, despite Glaxo cutting the price of AZT to prevent mother-foetus transmission of HIV, Zuma refused to approve AZT for such use - at the time outrage was focussed on HIV denialism charge, but is it possible that the ANC had too much invested, if not financially then surely politically, in the development of Virodene as an alternative? It certainly seems that way, as the decision to deny AZT to HIV+ mothers was taken just as a Phase I trial for Virodene eventually got under way - not in S.A, where it was stull illegal, but in... Guy's Drug Research Unit, London. To this blogger's knowledge, the results of this trial have never been published. Another trial was carried out on AIDS patients, this time in Tanzania. After treating AIDS patients with Virodene in a double-blind trial, this Phase II study yeilded

statistical analysis [that] revealed that Virodene was no cure for HIV/AIDS. It
had no effect on the HI virus, although some marginal improvement in the CD4+
count seems to have been recorded. For those invested in Virodene these results
were, quite obviously, a massive disappointment


Again, no published data are available from this trial.

As soon as it became clear the Virodene had no proven efficacy, that there was no hope for this "novel treatment," Mbeki's goverment permitted the distribution of AZT and other anti-retrovirals to pregnant women and victims of rape. No doubt too late for the hundreds, perhaps hundreds of thousands, of children born in the four preceding years who unnecessarily contracted AIDS through maternal transmission.

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AIDS continues to be a deadly scourge, and it is of course overly simplistic to view AZT as some magic bullet that will eradicate this killer disease. Nonetheless, where solid evidence existed for AZT's efficacy, ignoring it in favour of an unproven but potentially politically convenient alternative, has surely cost lives. Policy making really does have an impact on the lives of millions of people, and where lives and livelihoods are at stake, scientific rigour, evidence-based decisions and a strict detachment of political parties from pharmaceutical research are all critically important, as this tragic story goes a long way to showing.

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