Ethics of translational medical research.

Translational research is the science of application of basic research knowledge to develop novel methods of improving public health outcome. This review briefly discusses the various phases involved and the hurdles faced in the translational pathway, how translational science originated, and the infrastructures consigned for translational research. Translational research also faces numerous diverse ethical issues similar to those observed in biomedical research. The various types of ethical issues faced whereas conducting translational research are discussed briefly in this review to help researchers identify and prevent unethical practices while conducting or regulating translational research.

“I have been impressed with the urgency of doing. Knowing is not enough, we must apply. Being willing is not enough, we must do.”

Translational research has been widely described as “knowledge transition,” i.e., the transfer of knowledge from bench research to clinical practice, public health and policies, and vice versa, thereby leading to improved methods of diagnosis, treatment, and prevention. The issue faced in translational research is the wide pace between the discovery and its development and implementation. Broadly, translational research can be classified as two-phase research: T1 research (Bench-to-approval, preapproval or phase 0-III research) and T2 research (Approval-to-community, postapproval or phase IV).[1] Recently, the transitional pathway has been described as 4-phase, 5-phase, or 6-phase research: T0-T5; T0 – bedside to bench transition, T1 – basic research, T2 – preclinical research, T3 – clinical research, T4 – clinical implementation, and T5 – public health implementation. Operational research is an allied discipline where mathematical analytical methods are utilized for designing better public health policies and decisions.[2] Although the steps and route of translational pathway seem effortless theoretically, numerous skills such as designing a good clinical trial, accomplishing a multidisciplinary workforce, raising funds, compliant interactions with the regulatory agency, securing a patent etc., need to be mastered to narrow the pace between the discovery and implementation.

Numerous infrastructures have been developed globally to facilitate translational research. It began in 2003 when National Institute of Health (NIH, Bethesda, USA) began drafting the roadmap to reengineer translational health sciences. In 2008, private foundation – “Bill and Melinda Gates Foundation” started collaborating with various countries to create “deliverable technologies” against common diseases affecting the developing countries.[3] In 2012, NIH established a dedicated center – National Center for Advancing Translational Sciences to execute the translational science process. Similarly, in the year 2006, the European Strategy Forum on Research Infrastructure to facilitate translational medical research introduced the European Advanced Translational Research Infrastructure in Medicine, a pan-European infrastructure. Similar infrastructures that have been introduced globally to promote translational medical research include the Center for Drug Research and Development in Canada, Office of Translational Research in the UK, Therapeutic Innovations Australia in Australia, and Translational Health Science and Technology Institute in India.[45]

Translational research poses ethical issues similar to the ones observed in basic clinical research. Yet, many authors opine that the ethical issues faced by translational research science are diverse and complex. The translational process has been described to compose three basic elements: phases (as described above), gaps, and data transfer. These phases of translational research are separated by translational gaps, i.e., obstacle/delay encountered in transition to the next phase (e.g., lack of scientific or intellectual content and financial/regulatory support). Data transfer is the transfer of scientific content during transition to next phase. The ethical challenges faced by translational research depend on the element of the translational process. The various phases of translational research face ethical issues similar to the biomedical research ethics such as informed consent, animal bioethics, conflicts of interest, social injustice, and risk analysis ethics. The translational gaps confront ethical issues of resource/fund allocation whereas data/information transfer suffer ethical issues with confidentiality of data.[2]

Prior starting a translational process, extensive risk-benefit analysis needs to be undertaken to minimize potential harm at the research subject and population level against the benefit of researcher's curiosity, bearing in mind the consequentialist approach. The importance of a clear informed consent in translational research is to avoid therapeutic misconception, i.e., erroneously attributing therapeutic intention to research procedures or unreasonably judges' medical benefit from participation in the research.[6]

Financial conflicts of interest are a critical ethical issue likely to be faced commonly during the preapproval phase of translational research. Profound financial interconnection between the fund sponsors and research scientists can act as confounders due to issues such as patenting. Such conflicts can lead to nondisclosure of (1) risk information to participants and (2) negative results in publications. In this era of translational research, social injustice is one of the crucial ethical concerns. Resource-rich countries conducting translational medical research in resource-poor countries are common and if the results of the research are not expected to be beneficial/less beneficial to the resource-poor country, then arises the issue of social injustice and disparity. Examples include research undertaken on diseases that are rare or the resulting intervention/product is too expensive to implement, in developing countries. The gaps/obstacles between the phases of translational research also encounter ethical issues with regard to the allocation of funds/resources. These depend on the nature of the research, their chances of success, and impact on public health. Fund allocations occasionally tend to favor research processes which have a higher chance of success and commercialization than those with higher impact on public health but difficult to conduct and/or has less chance of success. The data generated at the end of each phase particularly in the early translational research phase suffer ethical issues of data protection/confidentiality. Sharing of research data at inappropriate stages of research could lead to risks of early unauthorized implementation leading to dangerous consequences such as untoward adverse effects or bioterrorism. Research data/information management needs to be extensively analyzed during the risk-benefit analysis in the early phase of translational research.[124]

Translational research ethics, although not completely new, is a revolutionary, diverse, and distinct field of biomedical ethics. Since the translational research framework is relatively new, insights on the various ethical issues are necessary to identify and prevent unethical practices while such research process is undertaken. The consequentialist approach should be the prime concern in translational science, i.e., well-being of the research participants and the society should be the priority than the advancement of knowledge.

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Conflicts of interest

There are no conflicts of interest.