Biomedical research on human subjects. Safety and efficiency

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We are constantly hoping for new information about drugs and procedures that will enable us to fight cancer, cardiovascular diseases, or AIDS more efficiently. Who wouldn't like to live longer and in good health?

Biomedical tests improve the quality and length of our lives. We would still be suffering from numerous diseases if new drugs were not tested and introduced on the market.

The tests of a new drug or medical procedure must first be done on models. Some of these are computer models, but animals can also be used in scientific research. If tests on models confirm the efficacy of new pharmaceutical substances (or medical products and procedures), then clinical tests on human subjects are initiated.

Safety first

Previously, medical experiments on humans usually took the form of auto-experimenting: doctors or scientists tested the new substance on themselves and sometimes also on their family members. An important figure in the history of medicine is Lady Mary Wortley Montagu, who, based on existing knowledge, decided to experimentally vaccinate her children against smallpox. The success of this test resulted in a series of vaccinations for members of aristocratic families. This is considered an important milestone in the development of vaccinology, the area of medicine related to vaccines.

The development and impressive progress of biomedicine has also been accompanied by abuse and scandal. An example of such abuse is the Tuskegee syphilis study, whose victims were several hundred African American farmers infected with syphilis. A similar incident occurred when mentally disabled patients of the American Jewish Chronic Disease Hospital were injected with live cancer cells. Most commonly accepted legal and ethical mechanisms protecting the participants of biomedical experiments were developed as late as the second half of the 20th century. These mechanisms take the form of recommendations on ethically performing tests on human subjects. For example, a part of the verdict in the trials of doctors who conducted cruel experiments was the so-called Nuremberg Code, which lists ten principles for human experimentation. It states, for example, that the human subject should be at liberty to bring the experiment to an end at any time (point 9). Currently, the most influential international document on the subject is the Declaration of Helsinki, which is discussed and updated every few years. These updates enable the document to take into account new aspects in the development of biomedicine and subsequent arguments developed by bioethicists.

"The task of our research team," Marcin Waligóra, PhD, says, "is to develop new and improve existing tools that facilitate the ethical assessment of biomedical experiments on human subjects. Together with Jan Piasecki, PhD (Jagiellonian University), and Vilius Dranseika, MA (Vilnius University), we focus on the methods of risk assessment in biomedical research on human participants, the conditions of participation in clinical trials of vulnerable groups (e.g., children), and the principles of ethical random selection of test participants. We are also planning to elaborate on the ethical postulates that accompany the conducting of epidemiological studies," he adds.

"The results of our work were presented, among others, in an article analyzing the structural causes of inconsistencies in the organization and supervision of clinical trials in Poland, which were revealed by the inspections carried out by the National Supreme Audit Office. In spite of a quite satisfactory legal status, we are still facing problems characteristic for societies in the transitional period, as modern legal solutions are confronted with outdated categories, definitions, and habits. Most of them are simply considered as another administrative burden. General principles are not always followed by specific procedures, either. Polish regulations on bioethical committees (organizations evaluating proposals of biomedical experiments on humans) are rather enigmatic. There is also no such authority that would effectively coordinate their work. This is why the British "Journal of Medical Ethics" published our commentary, in which we propose the uniformization of functioning of such ethical committees within the European Union. We believe that this would improve the safety of future test participants, but it would also make the life of scientists easier," Waligóra concludes.

Photo: © Elisanth |

How to regulate research on children?

Can children participate in biomedical research? An individual's participation in tests carries the risk of damaged health, and in extreme cases, even loss of life. On the other hand, the participation of children in tests is the only way to obtain common access to safe drugs for young patients. How can we solve this dilemma?

The task of bioethicists is to develop a mechanism that would protect the participant to a maximum extent, but would work in a way that would also enable the obtainment of key results in the course of conducted research. An example of such a mechanism in the case of children is the minimum risk standard, which permits their participation in the experiment if the threat of dangerous consequences is slight. Obviously, it is also necessary to respect the objections of the young patient. However, many scientists claim that current standards limit the development of new pediatric drugs too strongly. The form and quality of future regulations also depends on the results of the work of bioethicists. "As far as the issue of children's right to co-decide about their own participation in a biomedical research is concerned, international regulations remain inconsistent. We have developed arguments for increasing the rights of children to object with regard to their participation in so-called non-therapeutic experiments. The article on this subject was published recently on BMC Medical Ethics," a scientist from the Faculty of Health Sciences informs.

Randomization dilemmas

In the case of a double-blind random selection of patients, i.e., randomization, neither the patient nor the scientist (physician) knows which group of patients receives the tested drug and which one receives a placebo or comparator, i.e., an efficient drug authorized on the market. This is a way to eliminate prejudice and initial assumptions concerning the efficiency of the pharmaceutical product or procedure being tested.

However, the practice of conducting randomized tests has raised some ethical doubts from the beginning. Immediately after World War II in Britain, tests were conducted on the effectiveness of streptomycin in the treatment of tuberculosis. Previous tests on animals suggested that this antibiotic was highly effective. The need to obtain credible results from a methodological point of view forced the scientists to conduct randomized tests. This meant that instead of being subjected to experimental therapy, some of the patients underwent standard therapy, which was quite inefficient in those days. This story makes us realize that in randomized tests, one group of patients loses rather than gains.

A correctly conducted randomized test may, for example, reveal medical superstitions. In 2002, results were published with the aim of confirming the efficiency of arthroscopic knee surgery in fighting osteoarthritis. The belief in the efficiency of the procedure was common, and annually approximately 250,000 Americans underwent the surgery. During the experiment, patients were divided into two groups—one was subjected to arthroscopies, which were the standard treatment in such cases, while the other was subjected to sham surgeries (including, among other things, incision of the skin). The study did not confirm the efficiency of arthroscopic surgery in osteoarthritis, as no differences were noted between the efficiency of a placebo and actual arthroscopy.

Waligóra says: "I often hear questions about the practical applications of the results of our studies. In our project, we deal with so-called fundamental research. The results may have a form of recommendation concerning the improvement of existing procedural standards. Recommendations can be both local, e.g., concerning the binding principles of conduct in a given institution, and international. Our aim is to develop tools which will have an actual application."

The project is a continuation of the cooperation of team members initiated within the international program financed by the National Institutes of Health (USA). The results of the cooperation include, among others, the publication "Biomedical research with human subjects. International regulations," edited by Joanna Różyńska and Marcin Waligóra.

Research team from the Jagiellonian University: Marcin Waligóra, PhD — Principal Investigator; Jan Piasecki, PhD; Vilius Dranseika, MSc

In the years 2012-2013, Joanna Różyńska, PhD, from the University of Warsaw, participated in the work of the team.