Clinical Research and Clinical Care

Clinical Research and Clinical Care

Although much clinical research takes place in clinical settings with people who have or are at risk of illness, there are important and ethically relevant differences between clinical research and clinical care that all clinical investigators should be aware of. Differences include goals, methods, justification of risk, and level of uncertainty.

Goals: As described above, the goal of clinical research is to generate knowledge that will help us understand and optimize human health. The goal of clinical care, in contrast, is to diagnose, prevent, treat and care for an individual patient or group of patients with the goal of meeting their needs and providing benefit. These goals can sometimes coincide, but they also can and do come into conflict. Recognizing the differences and tensions can help clinical researchers to negotiate the conflicts.

Methods: The methods of clinical research and clinical care are also different. Clinical trials use methods such as randomization, dose escalation, blinding, use of placebo, procedures scheduled according to study design, and other methods that would be unusual or unacceptable in clinical practice, and which often restrict treatment flexibility for the individuals who are enrolled.

Justification of risks: In clinical practice, the risks of diagnostic procedures and treatments are justified by potential medical benefit to patients, whereas in clinical research, participants are asked to undergo procedures that carry some risk of harm or discomfort for scientific reasons, justified by the anticipated value of the knowledge.

Level of uncertainty: In clinical practice, decisions about treatment interventions and disease management are based on what is known through evidence and/or experience. In contrast, in clinical research, uncertainty is the starting point. An investigator asks a research question to decrease uncertainty, to gather knowledge about what is safe and what works.

If clinical investigators recognize these important differences and the ethical underpinnings of each activity; it can help clarify where clinical research and clinical care coincide and where they conflict. This understanding can help investigators make clearer decisions about study design, methods, potential risks and include protections for the enrolled human subjects.

The Eight Ethical Principles

1. Collaborative Partnership
2. Social Value
3. Scientific Validity
4. Fair subject selection
5. Favorable risk-benefit ratio
6. Independent review
7. Informed Consent
8. Respect for human subjects

1. Collaborative Partnership

To be ethical, clinical research should be planned and conducted in collaboration with the community in which it occurs.

This requires:

• Community participation in planning, conducting and overseeing research, and integrating research results into the local health system
• Demonstrating respect for values, circumstances, social practices, and existing health care services
• Sharing responsibilities and rewards of research with community partners

Collaborative partnership can be achieved by:

• Partnerships that promote integration of research findings into health care
• Community advisory boards
• Patient advocates on scientific advisory boards
• Advocates for research
• Other forms of community engagement

2. Social Value

To be valuable, clinical research should answer a research question that advances generalizable knowledge that can lead to improvements in health.

To have social value, research should answer a question that is useful for improving our understanding of human health and disease, or investigating methods of more safe and effective prevention, diagnosis, or treatment of humans. Social value entails consideration of who the beneficiaries of research will be and how they will benefit from the knowledge. To be valuable, research results do not have to be positive, negative findings can also be very scientifically or clinically valuable. Research does not satisfy the requirement of social value if it answers a question that is already known, overlaps already proven results, asks a question that is not generalizable, or if it involves a trifling hypothesis; results that are unlikely to be disseminated; or testing an intervention that cannot be practically implemented.

Research without social value diverts resources, such as funds or personnel, from more worthy pursuits, but more importantly exposes subjects to potential harm for no good reason.

IV. Elements of Ethical Research continued

3. Scientific Validity

To be ethical, research should be designed and conducted in a way that will result in reliable and interpretable data and be feasible. In this sense, good ethics depends on good science. The study should be designed in a way to realize the scientific objectives without unnecessarily exposing subjects to harm, denying them services they are entitled to, or requiring services that are not feasible. If research is not designed and conducted in a way that results in useful and interpretable data, it places people at risk for no reason. Scientifically valid research should:

• Be conducted in a methodologically rigorous manner
• Have a clear scientific objective(s)
• Be designed using accepted principles and methods that will achieve the scientific objectives
• Have sufficient power to test the objective
• Offer a plausible analysis plan

Examples of research that does not satisfy the requirement for scientific validity might include:

• Studies with a design unlikely to achieve the objectives
• Studies that do not include or cannot enroll sufficient numbers of participants to meet the objectives
• Studies with biased end points or statistical tests
• Studies in which the data are not carefully managed

It is the policy of the NIH that each protocol must undergo Scientific Review by the laboratory or branch prior to ethical review by an Institutional Review Board (IRB) to ensure scientific validity.

4. Fair Subject Selection

Subject selection should take into account the goal of fair distribution of the benefits and burdens of research, both to participants and to beneficiaries of the knowledge generated. Although individuals do not have a ‘right’ to participate in research, they have a right to be treated fairly and not discriminated against. In order to fairly select human subjects for research, the following should be considered: