Human experiments

Human participation in clinical trials requires consent. Although there are documents that protect the participants, it turns out that there are cases where the pharmaceutical companies took advantage of the residents in an unethical manner

Rafael Shalhav Galileo

Clinical trials of drugs and new medical developments are a fundamental and important part of the process of approving them for widespread use. Every new drug and every development may save lives or improve their quality, but they may also cause harm.

Therefore, naturally, before the Ministry of Health and similar bodies around the world approve pharmaceutical companies (companies engaged in drug development) to market new products, they are almost always required to conduct clinical trials - human trials - that will prove the effectiveness of the marketed products and their safety.

These trials are designed to minimize the risk of using a new drug and to expose to it only people who have agreed to participate in the trial, and to do so under the close control of doctors who follow every step of it.

Reducing risks: the Helsinki Committees and tort law

In order to reduce the risk involved in a medical experiment, there is a wide set of rules and instructions that severely limit the steps of researchers and companies wishing to conduct an experiment. The main legal tool at the center of this system is the Helsinki Committees - committees composed of doctors and public representatives, whose role is to approve or reject requests to conduct clinical trials on humans.

The committees were established in accordance with the "Declaration of Helsinki" - a document drawn up in 1964 by the World Medical Association and which centers the basic principles for conducting clinical trials. At its core is the obligation to conduct experiments in accordance with accepted scientific standards, based on an assessment of the risk versus the benefit of the experiment, and the need to obtain the consent of the participants in the experiment, except in exceptional cases.
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The Helsinki committees that exist in the hospitals, and the higher committee that gives approvals in cases of special experiments, are administrative tools that make sure that every human experiment is done under supervision and protects the interests of the participants. Among other things, the Declaration of Helsinki makes sure that in any medical research every patient participating in the experiment, even if he is in a control group, will be guaranteed the best method of diagnosis and treatment at the same time or in addition to the experimental procedure. The degree of effectiveness of the committees often depends on the degree of political power, the level of involvement, the principled positions, and the qualifications of the committee members.

Another important tool in minimizing the risks arising from clinical trials are tort laws: the right of a person who participated in a medical trial to claim compensation from the person who performed the trial, if it did not comply with the rules established by law and rulings. In the past, patients injured in various medical procedures were only entitled to compensation for physical damage caused to them because of the procedure they underwent (for example if they were disabled or their condition worsened), but starting in the nineties of the last century, the Israeli courts recognized the patient's right to receive compensation for physical damage as well The violation of his autonomy if medical treatment was performed on him without his full consent.

According to this right, a doctor who offers a patient a medical procedure, except in emergency cases, must inform the patient of the nature of the medical procedure, the risks involved, the expected benefit and the chances of its success. In addition, the doctor must inform the patient if the procedure he is undergoing is still considered innovative.

These rules, which developed in various rulings, were anchored in 1996 in the Patient's Rights Law, they are also mentioned in the "Public Health Regulations (Medical Experiments on Humans)", which oblige doctors to act in accordance with the Declaration of Helsinki. It should be noted that for several years the Knesset has been working on enacting a law that will replace the somewhat outdated regulations, and will extensively regulate the subject of clinical trials and the rights of the participants in them.

The pharmaceutical company must maintain the rules of ethics. Photo: A.S.A.P. Creative | Gina Sanders, Shutterstock
Different countries, different rights

The protection of the rights of participants in medical experiments is a relatively new matter. The first time such rules were widely formulated was in the "Nuremberg Code" formulated in 1947 in response to human experiments conducted in Germany during the Nazi regime. The rules established in the Code found their way into the Declaration of Helsinki, but the Declaration itself is not a legal document that countries and pharmaceutical companies are obliged to comply with.

Therefore, the actual protection of participants in experiments depends on the degree of protection each country chooses to grant to its citizens in the laws and regulations it enacts. Accordingly, there is a huge gap in the degree of protection granted to the citizens of different countries, since many countries have not properly regulated the system of protection for participants in experiments, and they are not on par with developed countries.

In some countries there is no protection at all for the citizens, but usually the security situation of these countries is so bad that the pharmaceutical companies cannot enter them. Even in Israel, the protection given to patients with limited decision-making capacity (e.g. Alzheimer's patients) and people in custody (e.g. prisoners) is limited only to the question of who will approve the experiment with their participation - the director of the hospital where the experiment is conducted or a higher level. The protection of soldiers who participated in medical experiments also made headlines several years ago, due to an experiment with an anthrax vaccine called "Omer 2".

In the experiment, which was carried out on regular soldiers, proper standards of supervision were not met, and some of its participants petitioned the Supreme Court. Following the petition, the standards for experiments in the IDF were regulated in an internal procedure, but the overall regulation of the rights of patients at risk, prisoners and soldiers is also awaiting the approval of the bill that is in the legislative process.

This issue takes on a threatening meaning when one examines the array of relations and powers between the various countries. Although most of the clinical trials in the world are carried out in Western Europe and North America, there is currently a clear trend among pharmaceutical companies to move to conducting clinical trials in the countries of Eastern Europe, Asia, South America and Africa. The presumed reasons for this trend are the low cost of conducting the experiment in a foreign hospital, the large number of patients compared to industrialized countries, and unfortunately, also the low degree of protection for the participants in the experiment and the relative ease of recruiting them.

In contrast to advanced countries, many of the countries where the number of clinical trials has increased are not able to effectively monitor this type of trials, and therefore the administrative protection for trial participants is low. Moreover, in some countries the experimenters are able to offer patients a payment for their participation in the experiment in an amount that exceeds their annual salary. On top of that, the lack of a proper medical system means that apart from participating in the experiment, there is no other treatment that might improve the condition of the patients.
In no choice

A chilling example was revealed due to the cholera and meningitis epidemics that attacked Nigeria in 1996. To fight the epidemics, many human rights organizations began emergency operations to vaccinate and treat the local population, and next to them, the American company Pfizer started a clinical trial of an antibiotic that was new at the time: trovafloxacin. According to what is alleged in a lawsuit filed later in the United States, many patients did not know the difference between the aid stations of the human rights organizations and the Pfizer research station and approached it as well to receive treatment for themselves and their children.

One hundred children received the experimental antibiotic developed by Pfizer and five of them died. Another 100 children received ceftriaxone, an antibiotic whose effectiveness is proven, but at a lower dose than usual. Six of them died. Although it was not proven that the children died due to the medical treatment given by Pfizer, the parents of the children who received the experimental drug claimed that at no point was it explained to them that their children were participating in the experiment, and that they were not given a choice regarding this matter. The claims were backed up by senior officials of the "Doctors Without Borders" organization. In August 2011, after 15 years of legal battle, the Pfizer company agreed to pay compensation as part of a settlement with the parents of the children who died.

The lack of balance in the allocation of resources between the countries of the world does not disappear from the world of drug development either, and in the absence of public medical services, most of the life-saving drugs are beyond the reach of the citizens of the developing countries. Copyright laws protect the patents that pharmaceutical companies registered regarding original drugs they developed, and prohibit competing companies from "copying" the active ingredient and selling it as a competing drug (generic drug) for several years after the original development was registered.

The laws are designed to encourage companies to invest in research and development, but they also prevent competition in the new drug market, and raise the price of life-saving drugs. Thus, a situation is emerging where citizens of developing countries take on more of the risk of developing new medicines, but do not enjoy the profit on the side of development.

Although, in the western countries, the drug administration of each country requires evidence regarding the ethical conditions in which human experiments were carried out, but the ability of the drug administration to supervise experiments conducted outside the country's borders is very low. In recent years, human rights organizations and the World Health Organization have also been involved in developing rules for managing clinical trials in developing countries and assisting those countries in enforcing international rules. However, it seems that the situation is still far from satisfactory.

The writer is a lawyer and a doctoral student at the Faculty of Law at Tel Aviv University.

for further reading

Glickman et al, Ethical and Scientific Implications of the Globalization of Clinical Research, The New England Journal of Medicine 360;8 (2009).

Maiga et al, Regulatory oversight of clinical trials in Africa: progress over the past 5 years, Vaccine. 2009 Dec 9;27(52):7249-52

The full article was published in Galileo magazine, January 2012