The case of Ivermectin
An ethical approach to off-label use of experimental interventions for the treatment of COVID-19 in JamaicaTuesday, June 15, 2021
In February 2021 the Medical Association of Jamaica (MAJ) publicly requested the authorisation of Ivermectin for the prevention and treatment of patients with COVID-19 in Jamaica. The article published in the Jamaica Observer quotes the MAJ: “Ivermectin has been safely used for decades in the effective treatment of certain parasites in humans.
“Potent anti-inflammatory and anti-viral properties have now been demonstrated against SARS CoV-2. A significant body of peer-reviewed evidence has now emerged, pointing to the fact that Ivermectin may decrease the case count and mortality rates when used as a prophylactic agent and when used in the treatment of all stages of COVID-19. The safety profile of this drug is well demonstrated after 40 years of clinical use.”
In response to the article, the Ministry of Health published on its website on March 2, 2021 reported that the Government is not in the position to make a policy decision on the use of Ivermectin for the treatment of COVID-19. However, Chief Medical Officer Dr Jacqueline Bisasor-McKenzie notes, “We recognise, however, that in patient-doctor relationships some doctors and their patients are using the medication for treatment of COVID-19 based on the available information. This is ideally done in the framework of a clinical study. In these situations there should be discussion and agreement between patient and doctor and appropriate documentation and follow-up.
The scenario mentioned above described by Dr Bisasor-McKenzie is off-label prescribing — the use of a drug approved for one condition in the treatment of another condition. Off-label prescribing has been done for many years, especially in cancer treatment; however, the practice remains a very delicate legal and ethical situation, especially when it is being suggested for widespread use to treat a still being explored condition such as COVID-19.
Several things should be considered with off-label prescribing and dispensing, one of which is therapeutic misconception. A therapeutic misconception is a situation in which the lines of treatment and experimentation are blurred in the minds of the patient or research subject. Although therapeutic misconception is primarily considered in a research setting, for example, clinical trials, it is not far-reaching to consider the implications in regular private practice.
While clinical trials are carefully vetted before the commencement of the trials by an ethics committee, and there is oversight for the protection of the research subjects, this controlled situation does not exist with off-label prescribing. Most simply, in the off-label context, the drug is prescribed, the pharmacist dispenses, and the patient takes it. There may not be an informed consent form signed or process documented to ensure that the patient or surrogate decision-maker is fully aware of the risks and benefits of the treatment and agrees to accept these risks to gain the benefits.
Secondly, while the benefits of Ivermectin are being promoted widely based on the alleged sufficiency of clinical data to support its use and safety, the lobbyists have rarely shared the possible adverse effects of the drug in and of itself. Some of the adverse effects of Ivermectin identified during treatment of approved conditions, such as river blindness, and documented in peer-reviewed journals prior to the pandemic, include death, serious neurological and non-neurological adverse effects such as coma, motor deficit, severe headaches, muscle pain, joint pains.
If the drug Ivermectin is to become available and used off-label for the treatment of COVID-19 in Jamaica, prescribers, dispensers, and patients should carefully consider the implications of off-label drug use, firstly, in relation to the patients, then their individual practice. It is easy to speak of the benefits of a product, especially when death is the alternative, but it is also essential to ensure that the competent patient is the one making these decisions and not just the clinicians.
Medical research and practice have come a long way since the publication of the Nuremberg Code of ethics and subsequently the Declaration of Helsinki on how medical doctors ought to conduct themselves. Clinicians should carefully apply themselves to ethical practice and not allow the stress and uncertainty of the current pandemic to cause us to abandon these established principles.
The WHO published guidelines for the use of off-label interventions in the absence of a controlled clinical trial setting: It can be ethically appropriate to offer individual patients experimental interventions on an emergency basis outside clinical trials, provided that no proven effective treatment exists; it is not possible to initiate clinical studies immediately; the patient or his or her legal representative has given informed consent, and the emergency use of the intervention is monitored, and the results are documented and shared in a timely manner with the wider medical and scientific community.
Clinicians who are lobbying for the off label use of Ivermectin or any other intervention may consider the following conditions to ensure that, in the absence of a clinical trial, the rights of patients are protected:
1) specify which physicians may be permitted to prescribe the drug/intervention, for example pulmonologist, internists, infectious medicine specialists;
2) the patients receive and understand all the necessary information regarding benefits, risks, and be made aware that the drug is an unapproved drug for the condition;
3) the patient or surrogate decision-maker signs a consent form;
4) the condition for which the drug is prescribed is stated on the prescription;
5) pharmacies that stock and dispense the drug will maintain records for the patients who receive the drug;
6) the pharmacists inform the patient or surrogate decision-maker that the drug is off-label (unapproved) for the condition and once again explain the possible side effects;
7) the patient or surrogate decision-maker signs a pharmacy consent form that he/she has been counselled regarding the drug;
8) the patient or surrogate decision-maker is made aware of the emergency contacts in case of adverse effects;
9) information is collated by the physician/pharmacy and sent to the Ministry of Health; and
10) the collated information could inform future policy decision by the Ministry of Health.
The lobbying of Jamaica's Ministry of Health for approval of Ivermectin for the treatment of COVID-19 is far-reaching, especially since two of the most influential global drug regulatory agencies in the US and Europe have yet to approve the drug. At this stage, the MAJ and other lobbyists are best positioned to comply with the law that Ivermectin is an unapproved drug in Jamaica for the treatment of COVID-19, and focus more so on how best to approach the situation in an ethically appropriate way.
The WHO has published guidelines on the use of experimental drugs in the document 'Monitored emergency use of unregistered and experimental interventions' that states: The decision to offer a patient an unproven or experimental treatment is between the doctor and the patient but must comply with national law. Where it is possible and feasible for the treatment to be given as part of a clinical trial this should be done, unless the patient declines to participate in the trial. If it is not possible to give the treatment as part of a clinical trial, appropriate records of the use of the medicine must be kept, in compliance with national law, and outcomes for patients should be monitored and recorded. If early results from an unproven or experimental treatment are promising, the treatment should be studied in the context of a formal clinical trial to establish its safety, efficacy, risks, and benefits.
The MAJ and other groups should consider placing their efforts on a more sustainable and practical petitioning for the Government to develop or adopt a policy for an ethical approach to using experimental interventions as an alternative to lobbying for individual drugs.
Shereen Dawkins Cox is a pharmacist and ethicist who is currently a doctoral research fellow at the University of Oslo, Norway, and president of the Bioethics Society of the English-speaking Caribbean. The opinions expressed here are not those of the organisations mentioned. Send comments to the Jamaica Observer or email@example.com.
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