The recent decision of the SA Health Products Regulatory Authority (SAHPRA) to allow for the dispensing of ivermectin, an anti-parasitic medication authorised for veterinary use, is a study in the law of unintended consequences. These consequences stem from misdirected lobbying for ivermectin’s use in patients with Covid-19 intersecting with the serialised weak governance that we have all become quite accustomed to.
The management of SAHPRA largely comprises some of our finest scientific and medicines regulation policy experts, who practice a vital and, for the most part, globally recognised regulatory function. Given its vital role in ensuring the safety and efficacy of medicines in the country, we can all take comfort from its imprimatur on the medicines we consume. That is as it should be and it is to the credit of those in its management, from the board to the executive, that they enjoy the confidence of the country in this task, despite the well-known constraints of inadequate budgets and resources, even at the best of times.
Pandemics, however, evoke exigencies and behaviour that test the institutions of society in ways not previously imagined. It was never imagined that the state would unleash an official response to the pandemic that has caused more harm than good, even if we are to cut the government slack because it performed no worse than other countries facing an unprecedented crisis, in a world wholly unprepared for it.
A case in point is SAHPRA’s new willingness to countenance applications for the approval, on “compassionate grounds” and in controlled circumstances, of the veterinary product for use in patients with Covid-19. To the casual observer, this might seem eminently reasonable. It is anything but. Here’s why.
SAHPRA has been made a scapegoat for the strident demands of various lobbies for ivermectin, supported by a well-resourced set of local and international advocates, some with medical credentials, such as the Frontline Covid-19 Critical Care Alliance (FLCCC), whose adherence to the truth is matched only by its vigorous advocacy of numerous small-scale trials that underpin its demands and which have been rejected by all major regulatory bodies worldwide, including SAHPRA, as inadequate.
In South Africa, those lobbying for the use of ivermectin include physicians and groups of unknown provenance, formed, it seems, specifically to advocate for its use, as well as misguided entities like AfriForum, whose medical and scientific credentials are questionable, but which has nevertheless decided that this is no impediment to its strenuous promotion of the drug even to the extent of compelling SAHPRA through legal action to approve its use.
For the uninitiated, the approval of any drug follows legal and ethical prescripts, developed over decades, to ensure the suitability, safety and efficacy of medicines. History is replete with disastrous and tragic outcomes when medicines were not subjected to these tests before its normal use was approved.
Globally, there is convergence on the scientific method, the process governing research and development (R&D) generally and, in particular, of medicines and other scientific products. The gold standard of this R&D approach is randomised controlled trials (RCTs), a methodology practised in every jurisdiction to create the greatest possible confidence in the outcomes of medical research, such as for vaccines.
Ivermectin is a drug that was used widely to eliminate debilitating parasitic diseases in humans, such as river blindness, and which is now only available for human use in a few countries, with most, including South Africa, confining it to veterinary settings. It still may be used in the country in rare cases of parasitic infestation in humans that are unresponsive to other drugs, but only under strictly monitored exemptions.
In attempting to comprehend SAHPRA’s new disposition to the use of ivermectin, its previous stance on the drug is germane. It prohibited the drug’s prescription for Covid-19 because the promoters did not satisfy its stated regulatory requirements of proven efficacy through RCTs, as is the burden of proof for every other registered medication. The mainly anecdotal research and inadequate trials of ivermectin do not cross the regulatory threshold for approval by SAHPRA, or, for that matter, by the World Health Organisation (WHO), the US Food and Drug Administration, the EU European Medicines Agency and a whole host of other globally recognised regulators throughout the world.
The WHO and other bodies have, however, initiated the running of RCTs for ivermectin as was the case for hydroxychloroquine, when RCTs eventually found no benefit of the drug in Covid-19 patients. The University of Oxford and, locally, the University of the Free State and Stellenbosch University are among the sites for these RCTs on ivermectin. The results are expected in a few weeks. So far, so scientific.
Most medical professionals, myself included, will welcome proof that ivermectin works, even marginally, and the regulators should then have no difficulty in approving its appropriate use. If the trials prove unsuccessful, regulators will then be fully justified in prohibiting its use. All SAHPRA would have to do is await the trial outcomes and evaluate the results.
Instead, SAHPRA chose to suddenly alter its stated position. A regulatory body has to always proffer rational reasons for adopting a position in keeping with its objects and, equally, rational reasons to change that position. This is not a choice, but a constitutional injunction. Neither the management nor the government can override this injunction. The reasons publicly proffered for the change in SAHPRA’s position do not meet this test for rationality, although there may be as yet unstated information that may justify it, in which case those reasons must be made public too.
The commentary from SAHPRA alluded to the intense pressure, bordering on desperation, faced by doctors, patients and families in the strenuous and harrowing treatment of the condition, which is common cause. SAHPRA also expressed concern that the prohibition of the use of ivermectin was stimulating a black market trade in the drug, where unsupervised and clandestine use of uncontrolled dosages was causing harm.
Unreferenced, but quite evident, pressure from lobbyists, some bordering on incitement to harm against the management of SAHPRA, as perhaps concerns of rumoured death threats against the CEO and the fear of litigation by aggrieved parties should the drug eventually be found to be effective, might have also contributed to the decision.
That the entity would wish to avoid such eventualities is understandable, but it is, with respect, wrong. None of these reasons can account for altering the statutory remit of SAHPRA. The new position may be pragmatic, but it is expedient.
Dispense with shibboleths
Let’s dispense with the shibboleth of the real anguish of professionals during Covid-19 being ameliorated by abrogating what should be an iron-clad regulatory regime that is meant to protect the people. As health professionals, we’ve all been there and have the scars to prove it. The pressure on SAHPRA that this anguish evokes only finds purchase in the desperation of patients and their families.
As for the other stated and rumoured concerns, none of them, from the black market to unethical use of the drug, to the threats to the staff at SAHPRA and the fear of litigation, serious as they are, provide this rational basis for a change in the scientific regulatory position of SAHPRA in this instance. Only new and bona fide scientific evidence supporting such a change in position will do for a regulator. These other matters fall within the ambit of law enforcement.
The only comfort that SAHPRA can take to justify its change of position is that law enforcement in these matters is massively deficient due to the dysfunction in those spheres of the state. But even this, unfortunately, does not get around the legal remit of its functions.
The consequences of this decision are quite alarming. A precedent has been set that factors other than those explicitly outlined in the legislation that gives life to this body, may now influence its decisions. A proximate example is that of vaccines.
In the event that South Africa does not obtain sufficient supply of registered vaccines, as Europe is already experiencing, SAHPRA may now presumably register any vaccine that hasn’t met the approval standards it has required of others by invoking the same reasoning to get it registered for use, to wit, the extraneous pressures attending ivermectin being applied. The same will apply to any other medicine that has not met the scientific standards. Indeed, how could SAHPRA now refuse to register such a medicine?
The good folk at SAHPRA who have been forced into this action have at least channelled the applications for the “compassionate” use of ivermectin into the Section 21 framework, which allows for such compassionate approval. Perhaps this may slow down the various pedlars of the drug a little, but it will do little to stop the black market in its trade. It will, however, make the necessity to conduct scientifically valid R&D optional.
SAHPRA may have created a rod for its own back. Stretched as its resources are and seized as it must be with evaluating vaccines that we know work (unlike ivermectin), it will now have to contend with hordes of applicants baying to get their products to market, at up to R3,200 for four tablets that cost R40 in Bangladesh.
Government has been in the habit of eroding the constitutional investiture attending regulators, which are creatures of statute. The health sector, in particular, is replete with this kind of misgovernance, where the Health Professions Council of South Africa, Council for Medical Schemes and now SAHPRA are enlisted in political, commercial and emotive agendas that should not apply in a disciplined constitutional order.
Why did SAHPRA not stand firm and await the results of the trials it holds up as its standard for all other health products? Other regulators worldwide are doing so. Expect a downgrading of the professional esteem in which they now will hold SAHPRA. All because it was designed for a normal functional democracy and was unable to withstand abnormal pressure, nor able to depend on a strong government for protection.
When the only rules that act as a rational, fair and transparent governance of the use of medicines or any other public goods or commodities can be ignored, even under duress, we are well down the slippery slope.
It is not too late for SAHPRA to stand back from its decision. No one who understands the danger to its vital remit, that the current imbroglio has occasioned, will object. But it must then be properly insulated against such pressures in the future. In the age of pandemics, we need a SAHPRA that is strong, intact and with its fealty to its founding objects a warranty against uncertainty in medicine. DM/MC
Aslam Dasoo is a medical professional and veteran health activist with interests in health governance, policy and financing. As a convenor of PHF, his primary focus is on public healthcare, especially during the pandemic.
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