COVID-19 Clinical Trials: Are Physicians Violating the Helsinki Ethical Principles?
As early as 1964, the World Medical Association developed the Helsinki Declaration as a statement of ethical principles applicable to medical research involving humans.
This was a time not that remote from when Nazy Germany’s Angel of Death, Joseph Mengele, carried out numerous deadly experiments on prisoners in concentration camps.
Several updates of the “Ethical Principles for Medical Research Involving Human Subjects” have since been made, the last one dating 2013.
The declaration recognizes the need for research for medical progress, yet emphasizes:
“It is the duty of the physician to promote and safeguard the health, well-being and rights of patients, including those who are involved in medical research. The physician’s knowledge and conscience are dedicated to the fulfilment of this duty.”
Use of Placebo Should Not Permitted as Effective Treatments Exist
The use of placebo is covered in the Helsinki Declaration, which states that the benefits, risks, harms, and effectiveness of a new intervention should be tested and compared to those of the best existing proven interventions / treatments.
In other words, if there is an existing proven treatment, there should not be any usage of placebos, except in very particular cases.
The official position of WHO is that there is no proven treatment for COVID-19 and that, to date, no specific medication is recommended to prevent or treat infections with the new coronavirus.
WHO seems however to pay no attention, or to pay a blind eye, to research that has already been completed and reports that conclude that there is an effective treatment for COVID-19.
WHO’s stance is particularly worrisome considering the landmark study by Professor Didier Raoult and his Marseille team, covering 1,061 patients, which has shown remarkable success with early treatment of COVID-19 patients.
The Raoult study shows minimal needs for long hospitalizations, intensive care and ventilators. Yes there were a few deaths, but their number was particularly low when compared to usually reported case-fatality rates.
The patients who died in the context of that study were also pretty old: within the 1061 treated patients, there were 5 deaths, all in the 75 to 91 age bracket.
The results of this study were confirmed in a smaller recent study in Brazil, where there was a sharp reduction in the need for hospitalization, thanks to early treatment via telemedicine.
In the case of this Brazilian study, the treatment combined hydroxychloroquine, azithromycin and zinc, in a similar way as with the protocol developed by Dr Vladimir Zelenko in New York.
With more than 1,000 studies worldwide conducted under the “SOLIDARITY” WHO umbrella, including a multitude of randomized clinical trials using placebos, and with thousands of volunteer patients involved and recruitment still ongoing, one has to ask if WHO is not flouting the ethical principles governing the Helsinki Declaration.
Strong Ethical Principles Should Govern COVID-19 Clinical Trials
While not legally binding, the Helsinki Declaration has strong ethical principles and is usually considered as critical to respect for the design of any clinical trials.
The declaration clearly states that the use of placebos is only acceptable when there is no proven intervention, no proven treatment.
If there is a proven intervention, a proven treatment, the use of placebos is no longer permitted, except for a few limited exceptions.
These exceptions are situations where patients receiving placebo “will not be subject to additional risks of serious or irreversible harm as a result of not receiving the best proven intervention.”
Today, we know that in the case of COVID-19, there is a considerable additional risk of serious or irreversible harm when hydroxychloroquine-based treatment is not given.
Indeed, if COVID-19 is not treated early, with the Raoult or a comparable protocol, the risk of worsening the patient’s condition increases substantially, and this can lead to death.
The Raoult protocol combines hydroxychloroquine and azithromycin at safe dosage, during 10 days, with medical supervision and with 2 electrocardiograms. See details here.
There are variations of this protocol, for example recommended by Dr Vladimir Zelenko in New York, which combine hydroxychloroquine and azithromycin with zinc sulfate, for 5 days. See details here.
The Helsinki Declaration also stresses that “extreme care must be taken to avoid abuse of this option” of using placebos, when effective treatment is available.
Obligation to Thoroughly Inform Volunteer Patients
The Helsinki Declaration emphasizes the importance of free and informed consent, including about the expected benefits and potential risks of the research.
“No individual capable of giving informed consent may be enrolled in a research study unless he or she freely agrees.”
“In medical research involving human subjects capable of giving informed consent, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail, post-study provisions and any other relevant aspects of the study.”
According to this principle, patients voluntarily participating in clinical trials should receive full information, including about the existence of effective hydroxychloroquine-based treatments, before agreeing to participate, through written consent.
Not providing full information about the existence of effective therapies contravenes the Helsinki ethical principles. It allows researchers to ignore, or minimize the scope of, these therapies, when they seek the signed consent of volunteer patients.
Uninformed patients can be misled to accept the unacceptable, i.e. a choice between a placebo and a lower quality treatment, which both can be fatal or lead to long-lasting pulmonary or other health issues in the case of COVID-19.
It should be noted here that the WHO and a number of research institutes have made calls in the past weeks for volunteers, through the media, because they typically have difficulties to enrol enough volunteers to participate in the clinical trials for COVID-19 treatment.
It’s also known that, in countries such as the US, where there is information circulating among front line medical workers, there is lots of reluctance to participate in clinical trials, as medical workers usually know very well that they will receive placebo or treatment by random allocation, instead of through an informed assessment of what is most likely to be in their best interest.
Responsibility to Protect Vulnerable Groups and Individuals
The Helsinki Declaration emphasizes the obligation to protect vulnerable groups and individuals.
“Some groups and individuals are particularly vulnerable and may have an increased likelihood of being wronged or of incurring additional harm.”
“All vulnerable groups and individuals should receive specifically considered protection.”
Again, when we see that certain studies conducted under the WHO umbrella relate mainly to elderly people, sometimes 75 years or more, who are sick and highly vulnerable, It’s is therefore valid to challenge how such studies can ethically be conducted in the first place.
An example of a mega clinical trial involving highly vulnerable patients can be found in Angers, France, with 1300 patients, half of them under placebo, and the other half under a sub-optimal hydroxychloroquine medication, without azithromycin or zinc.
Researchers, Physicians Bear Huge Responsibilities
The Helsinki Declaration requires researchers to assess the risks, constraints and benefits.
“All measures to reduce the risks must be implemented. Risks must be constantly monitored, assessed and documented by the researcher. ”
“All medical research involving human subjects must be preceded by careful assessment of predictable risks and burdens to the individuals and groups involved in the research …”
“Measures to minimise the risks must be implemented. The risks must be continuously monitored, assessed and documented by the researcher.”
“It is the duty of physicians who are involved in medical research to protect the life, health, dignity, integrity, right to self-determination, privacy, and confidentiality of personal information of research subjects.”
“The responsibility for the protection of research subjects must always rest with the physician or other health care professionals and never with the research subjects, even though they have given consent.”
“Physicians may not be involved in a research study involving human subjects unless they are confident that the risks have been adequately assessed and can be satisfactorily managed.”
“When the risks are found to outweigh the potential benefits or when there is conclusive proof of definitive outcomes, physicians must assess whether to continue, modify or immediately stop the study.”
Maybe it’s time for physicians and researchers all around the world to take a deep breath and to assess whether to continue, modify or immediately stop their ongoing COVID-19 research, in light of the ethical principles of the Helsinki Declaration and the existence of effective early treatment.
This is especially true when the clinical trials rely on placebos,
About the history of the declaration: https://en.wikipedia.org/wiki/Declaration_of_Helsinki