such influencing factors exists, however, and it is impossible to state precisely where justifiable persuasion
ends and undue influence begins. But undue influence would include actions such as manipulating a
person's choice through the controlling influence of a close relative and threatening to withdraw health
services to which an individual would otherwise be entitled.
2. Assessment of Risks and Benefits. — The assessment of risks and benefits requires a
careful arrayal of relevant data, including, in some cases, alternative ways of obtaining the benefits sought in
the research. Thus, the assessment presents both an opportunity and a responsibility to gather systematic
and comprehensive information about proposed research. For the investigator, it is a means to examine
whether the proposed research is properly designed. For a review committee, it is a method for determining
whether the risks that will be presented to subjects are justified. For prospective subjects, the assessment
will assist the determination whether or not to participate.
The Nature and Scope of Risks and Benefits. The requirement that research be justified on the basis of a
favorable risk/benefit assessment bears a close relation to the principle of beneficence, just as the moral
requirement that informed consent be obtained is derived primarily from the principle of respect for persons.
The term "risk" refers to a possibility that harm may occur. However, when expressions such as "small risk"
or "high risk" are used, they usually refer (often ambiguously) both to the chance (probability) of
experiencing a harm and the severity (magnitude) of the envisioned harm.
The term "benefit" is used in the research context to refer to something of positive value related to health or
welfare. Unlike, "risk," "benefit" is not a term that expresses probabilities. Risk is properly contrasted to
probability of benefits, and benefits are properly contrasted with harms rather than risks of harm.
Accordingly, so-called risk/benefit assessments are concerned with the probabilities and magnitudes of
possible harm and anticipated benefits. Many kinds of possible harms and benefits need to be taken into
account. There are, for example, risks of psychological harm, physical harm, legal harm, social harm and
economic harm and the corresponding benefits. While the most likely types of harms to research subjects
are those of psychological or physical pain or injury, other possible kinds should not be overlooked.
Risks and benefits of research may affect the individual subjects, the families of the individual subjects, and
society at large (or special groups of subjects in society). Previous codes and Federal regulations have
required that risks to subjects be outweighed by the sum of both the anticipated benefit to the subject, if any,
and the anticipated benefit to society in the form of knowledge to be gained from the research. In balancing
these different elements, the risks and benefits affecting the immediate research subject will normally carry
special weight. On the other hand, interests other than those of the subject may on some occasions be
sufficient by themselves to justify the risks involved in the research, so long as the subjects' rights have been
protected. Beneficence thus requires that we protect against risk of harm to subjects and also that we be
concerned about the loss of the substantial benefits that might be gained from research.
The Systematic Assessment of Risks and Benefits. It is commonly said that benefits and risks must be
"balanced" and shown to be "in a favorable ratio." The metaphorical character of these terms draws
attention to the difficulty of making precise judgments. Only on rare occasions will quantitative techniques be
available for the scrutiny of research protocols. However, the idea of systematic, nonarbitrary analysis of
risks and benefits should be emulated insofar as possible. This ideal requires those making decisions about
the justifiability of research to be thorough in the accumulation and assessment of information about all
aspects of the research, and to consider alternatives systematically. This procedure renders the assessment
of research more rigorous and precise, while making communication between review board members and
investigators less subject to misinterpretation, misinformation and conflicting judgments. Thus, there should
first be a determination of the validity of the presuppositions of the research; then the nature, probability and
magnitude of risk should be distinguished with as much clarity as possible. The method of ascertaining risks
should be explicit, especially where there is no alternative to the use of such vague categories as small or
slight risk. It should also be determined whether an investigator's estimates of the probability of harm or
benefits are reasonable, as judged by known facts or other available studies.