Ethical issues in precision medicine

In precision medicine, the treatment and prevention of diseases are based on individual variability in genes, environment and lifestyle. It is a logical extension of current research using multiomics-based laboratory studies to profile and identify clinically actionable markers. In essence, the goal is to obtain genotypic and phenotypic information to direct accurate and effective treatment of the patient. Practical clinical applications to patients would typically require extensive and complex testing. Clinical laboratories will play a crucial role in the implementation of precision medicine in health care. Laboratory work will often require reflex testing based on algorithms or individual case decisions. Interpretation will be based on integrating laboratory results and clinical information. Indirect and direct reporting of laboratory results to patients also brings increased demands on the clinical laboratory to be a more interactive partner in clinical care.

Clinical laboratorians will need to rely more on ethics skills to meet these exciting changes. From a global perspective, formal education in ethics has been variable and often limited or absent from many training programmes. ¹ Many clinical laboratorians, therefore, feel poorly prepared to incorporate ethics into their skill set. One way to improve this situation is through more exposure to ethics. In this editorial, we describe ethical issues in precision medicine. Our perspectives are that of a medical geneticist/clinical laboratorian and a genetic counsellor.

Research and the sprouting clinical practice of precision medicine are based on big data-sets of research and clinical information and various multiomics-based laboratory studies. This setting can generate ethical dilemmas concerning issues like consent, additional findings, autonomy, privacy and justice. Balancing the needs of precision medicine and the principle that patients’ interests come first can create tensions that often remain unsolved.

In precision medicine, collection and analysis of data are more comprehensive than needed to investigate individual clinical situations. The data collected and research aims often change over time. This makes obtaining informed consent based on adequate counselling challenging. Dynamic consent that can change with time may solve some of the problems. In other situations, presumed consent will be considered adequate.

Although precision medicine is based on various data-sets, genomics remains central. Ethical issues in precision medicine, therefore, overlap with those in genetics and similar solutions are appropriate. In clinical genetics, recommendations have been made on how to do deal with incidental results, which are now preferably called additional or secondary findings. ² Additional findings are defined as findings concerning an individual, having potential health or reproductive importance and discovered during testing for an unrelated problem. To communicate medically actionable additional findings in genetic testing is generally accepted today, although there have been controversies about what findings to communicate and whether this practice should be mandatory or optional.

A second related issue is what to do if new information related to a patient’s diagnosis is found. The European Society of Human Genetics (ESHG) has recently published recommendations for this setting. ³ In clinical practice, re-contacting for updating patients with new, clinically significant information related to their diagnosis, or previous genetic testing may be justifiable. Each case should be evaluated for clinical and personal utility. Re-contacting is considered a shared responsibility between health-care providers, laboratories, patients and other stakeholders. In April 2019, the American College of Medical Genetics and Genomics published a statement on points to consider in re-contacting patients after revision of genomic results. ⁴ Similar to ESHG, they point out that there is no legal duty and that re-contacting is considered a shared responsibility of the clinician and clinical laboratory. The patient initiating the process of revaluation is understandably the most straightforward approach, but a plan needs to be in place if they do not.

Laws and policies on the return of genetic results in research vary. ⁵ The American Society of Human Genetics (ASHG), in collaboration with various stakeholders, recently published a policy statement on re-contacting research participants regarding new genetic findings. ⁶ ASHG strongly recommends that researchers make reasonable attempts to contact research subjects during the period of research funding. There is, however, no responsibility for researchers to hunt or scan the genomic literature for changes in variant interpretation. This statement is endorsed or supported by several organizations, including ESHG. It is essential that the policy of an organization and the consent form are clear on the return of results. The return of research results are in many ways similar to the return of results in clinical genetics, but magnified by the additional complexity and potential uncertainty of the results. A particularly thorny issue regards what to do if research participants have been told that no results will be returned to them. Facilitating participant access to results is often the best solution in this setting.

Privacy in databanks used in precision medicine is of significant concern, and there are examples of data profiles being used to identify persons in anonymous databanks. Under what circumstances should this be permissible, and how can data access be controlled to ensure privacy without compromising support for precision medicine? Working out the right criteria and balance of stakeholders in this area is in the early stages. An essential, invariant requirement will be that individuals have minimal information risk, i.e. no significant extra risk by having their data processed in the databanks.

Justice is based on fairness for all without discrimination. The focus is on how to deliver the gains and progress of precision medicine consistent with equal rights to health care. Research and clinical practice in precision medicine are expensive. Research data are mainly generated from wealthy populations, and results may not apply to other less privileged populations given differences in genetic makeup, environments and lifestyle. In practice, clinical testing on individuals will also be expensive, although increased efficacy of precision medicine could be cost-saving in certain situations. One thorny ethical dilemma in this area involves individual rights. If the state commits to equal access to precision medicine, can the state also require that people adopt precision healthy lifestyles in return?

Precision medicine is a buzzword carrying high expectations among professionals and patients alike. The field should avoid hubris, but rather carefully manage expectations and not promise more than the field can reasonably deliver.