2023-11-27 03:03:19
In response to the need for precision medicinesome scientists have moved from evaluating which interventions are safe and effective for most patients to more precise approaches designed to find the right treatment for a given person at the right time.
Scientific advances, initially in the oncological field, demonstrated that clinical categories might be subdivided into molecular endophenotypes, with different trajectories and therapeutic responses. Tissue atlases were created to describe different cell types and characterize individual pathological entities.
To promote research on kidney disease, in 2017 the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) held a workshop in which the scientific value and ethical acceptability of performing kidney biopsies were discussed, which raise a small but measurable risk of death, in people who do not need to undergo a biopsy for clinical care. The tissue might be examined using “omics” techniques (molecular research approaches such as genomics, epigenomics, proteomics and metabolomics) to elucidate previously unknown disease pathways and identify potential drug targets.
On this basis, in that same year, the NIDDK-funded Kidney Precision Medicine Project (KPMP) established six recruitment sites to obtain tissue from patients with kidney disease, in whom biopsies were not clinically indicated. During the first five years of the study, 156 biopsies were performed, 42 in patients with acute kidney injury and 114 in chronic kidney disease. There were no deaths, and complications, including symptomatic and asymptomatic bleeding, were consistent with those described in the literature and in the informed consent form.
Obtaining healthy reference tissue has the potential to boost research for a variety of conditions. But the risks posed by this vary depending on the accessibility of the tissue. The acquisition of “normal” brain tissue, given its relative inaccessibility and the importance of organ integrity and function, poses potentially substantial risks. Brain tissue obtained following a craniotomy was subjected to anesthesia, which may affect -omics analyses. The results of the first -omic studies single-celled specimens suggest that adjacent tissues can be used as nonpathological standards for histological analysis.
For several reasons, harvesting tissue from patients is more common and accepted than harvesting it from healthy volunteers. Patients may be more motivated than unaffected people to improve the treatment of their diseases. At the same time, patients run the risk of having therapeutic misconceptions, that is, assuming that research is the indicated care.
There is also concern regarding the additional burden this places on patients already living with the disease, and the risks associated with treatment. Given the importance of informed consent, voluntary decisions, and fair burden sharing, one might argue that obtaining tissue from healthy volunteers for research is not so bad ethically, and may be preferable, and in some cases safer, than obtaining it from patients. . This conclusion is supported by the fact that phase 1 research, which often poses a low but measurable risk of serious harm or death, is permitted in healthy people. Furthermore, in other contexts, consenting adults may accept high risks in their efforts to achieve valuable outcomes, as is the case with bone marrow and kidney donation.
Ethical discussions agree that there are limits to the level of risk to which participants in research are permitted to be exposed, which depend on the circumstances (social value of the study). Therefore, the approval of the studies should consider four important points.
First, when the risks are very low, one does not need to spend much time evaluating the social value of a study. On the other hand, those that present high risks to healthy volunteers should be approved only when they are certain that they have substantial social value.
Secondly, when research poses high risks, it should be carefully assessed whether these can be reduced. To minimize added risks, it might be valuable to develop a national system to track the tissue that has been collected and the studies that have been performed, so that researchers can determine whether a new trial actually requires additional biopsies to be performed.
Third, the standard consent process is typically assumed to result in adult participants understanding the research and giving valid consent. However, in the context of high-risk studies, it is particularly important to ensure that participants truly understand the implications of their participation.
As a fourth point, when the risks are high, it is essential to provide treatment and compensation for research-associated injuries, to address both short- and long-term harms. For example, in the case of kidney biopsies, blood transfusions or radiological interventions may be necessary.
Finally, research that poses greater than minimal risk to healthy volunteers requires different ethical analyses. The study may be ethically appropriate, but needs careful evaluation. Researchers and control bodies must guarantee that there is no less risky way to achieve the objectives set. They should also carefully evaluate the risk-benefit balance, including the social value of the information to be obtained. To ensure that risks are justified, -omics analyzes must be of the highest possible quality and reproducibility. Additionally, obtaining input from potential participants and healthy volunteers can help ensure the ethical appropriateness of the research.
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