Special Section: Clinical Research in Ukraine
Ethical Considerations: Clinical Research in Wartime Ukraine and Beyond
Chieko Kurihara
Kanagawa Dental University, Japan
Victoriia Dobrova
National University of Pharmacy, Ukraine
Francis P. Crawley
Good Clinical Practice Alliance – Europe (GCPA)

Strategic Initiative for Developing Capacity in Ethical Review (SIDCER)


ivilized society has constructed rules and protective measures to prevent repeating grievous human mistakes and to protect human health, safety, and rights. These include the CIOMS (Council for International Organizations of Medical Sciences) health research guidance on ethics, medical product development, and safety, the Declaration of Helsinki, and other guidelines which declare protection of life, human rights, and diversity of cultures.

The war in Ukraine delivered an unprecedented impact on the regional and global clinical research infrastructure and on the lives of current and future patients. Careful consideration for the ethics of research continuity during the current war may help to inform guidance for future responses in similar situations.

Many current guiding codes of ethics were established after detailed analysis and wide discussion of research that was clearly unethical and unacceptable. However, medical research in countries where military conflicts are taking place requires additional ethical attention and careful consideration. Previous human experience has shown that there is a high probability of developing negative tendencies and even unethical abuses in such situations. However, the research situation in Ukraine during this war is unlike previous ones. No one would say that the research itself is unethical. Nonetheless, these research studies are now taking place in a new challenging situation. We must reevaluate these projects taking into consideration the ongoing war.

General Ethical Considerations in Clinical Research

Clinical trials are an essential part of the Ukrainian healthcare system, and not only for clinical trial participants who need these often life-saving therapies. The ethical continuation of clinical trials is critical to protecting a critical component of the global medical research system.

Informed consent is the primary building block of ethical clinical trial conduct. It codifies the concept that it is acceptable to experiment on someone if that person agrees to the experimentation. This practice was later refined: Informed consent in and of itself is not sufficient; there must also be an independent review to confirm that the research and the participation of those patients, even with their consent, would be ethical. This introduced the concept and process of ethics review by institutional review boards or research ethics committees.

The international medical and ethics communities came together as the World Medical Association to refine this concept. The WMA Declaration of Helsinki clearly states that the reason we do research is to continually improve our knowledge and tools for responding to disease, suffering, and the healthcare needs of individuals and populations (Article 6). This is one of the justifications, if not the most important one: that the results of the research will be used to improve the medical community’s response to disease, suffering, and healthcare. Medical research on other people cannot be carried out simply for scientific curiosity or because there’s something we want to know. The justification for experimenting on another human being is that it will help future patients in that similar situation.

The Ukraine Clinical Research Support Initiative (UCRSI)

The Ukraine Clinical Research Support Initiative (UCRSI)

Research Ethics Committees (RECs) in Ukraine

The clinical research system in Ukraine can generally be described as decentralized. Each trial site must report to their local research ethics committee (REC). All RECs in Ukraine are independently managed and operated. Regulatory and ethical review and approval of clinical studies is a parallel operation: The State Expert Center of the Ministry of Health of Ukraine is the regulatory authority, and RECs execute review of clinical trials documents and all research materials and make independent approval decisions in parallel. National regulation of clinical trials is harmonized with international standards that ensure the high quality of clinical research.

The war in Ukraine brings unprecedented operational challenges to clinical research ethics. Electronic communications tools have not been completely implemented, so there is no strong interaction between RECs. RECs in Ukraine must conduct ethical monitoring applying mostly remote methods. Organizing REC meetings and communications is difficult. Procedures must not only ensure the safety of committee members (who are all unpaid volunteers). They must also consider the need to ensure clinical trial data integrity and confidentiality as well as that review deadlines are met, in conditions lacking electronic data flow.

Other challenges for local RECs in ethics review and monitoring in Ukraine are related to the committee members’ lack of experience in working under bomb and missile attacks and energy lockdowns. Regardless, RECs have to constantly evaluate risks to their committee members, study participants, site personnel, clinical data quality, and confidentiality, and generally ensure proper human subject protection remotely in difficult circumstances.


Ethical Uncertainty Presents Complex Dilemmas

Assessment of benefit and risk for each research subject should come first. However, what strategic ethical consequences and long-term ethical impacts should these benefit-risk assessments consider? RECs do not have criteria for assessment of risk to patients during active war or of the clinical trial site’s physical ability to continue clinical studies in wartime conditions such as in Ukraine. Are there consequences we can predict and perhaps even prevent?

The most acute issues for RECs: What is the best way to monitor and protect research subject rights in trial sites in Ukraine that are particularly challenged, inaccessible, or impaired? How should interactions between RECs and clinical sites hosting patients from trials in other locations in Ukraine or even abroad be managed? These hosting sites give these subjects help. But should Ukrainian RECs continue to manage and protect their rights?

Rules of Research, Rules of War

What is the price of the war regarding research? Patients suffer from disease because they can’t continue to participate in clinical trials, making patients more vulnerable. Scientists cannot participate in world networks, cannot continue to participate in global science projects, and cannot publish their results in global publications. In the current circumstances, many Ukrainian researchers have lost more than publication opportunities—they have lost their lives.

We must establish a relationship between the rules of war and the rules of research. Informed consent is really about the relationship between the research participant, the researcher, and the sponsor. We must figure out how to care for that relationship and bring it forward through the disruptive, destructive environment of war.
It’s important to have research for health in a peaceful situation. But it’s also important to have research for health in a conflict situation.

Mapping the Ethical Terrain of Research during Armed Conflict

Mapping the Ethical Terrain of Research during Armed Conflict

What Happens After the War?

The global clinical trials and research enterprise contributes significantly to worldwide wealth and prosperity. It contributes to the practice of medicine and to the development of new medicines and approaches to treatment. It contributes to science in society, and to education and public health. The clinical research enterprise, as part of modern, global interconnected research, is part of the self-identity and reality of Ukraine.

The current conflict demonstrates an ethical responsibility for our international community to support this research enterprise during and after the war. How do we respond to this responsibility to research patients and to this enterprise? Can we create national and regional REC and IRB networks in times of peace so these networks can buttress and support RECs and IRBs conducting research during a conflict? Can we refine the informed consent framework that protects research participants in peacetime to provide similar information and protection during war?

To ensure ethical research continuity during times of disruption, all stakeholders in the global clinical trials and research enterprise must lead the way in revising guidance and other documents and providing direction to clearly allow and encourage continuity, which will preserve progress for future generations.