Study Risk Level Definitions

The OUHSC GCRC defines study risk as minimal, low, moderate, or high. Criteria and examples for each are given below. The examples cited for each level of risk category can be used as a general guide. Any concerns or questions not addressed on this page should be referred to the GCRC Research Safety Advisor, Dr. Steven Chernausek.

Minimal Risk - The probability and magnitude of harm or discomfort anticipated in the research are not greater than those ordinarily encountered in daily life or during routine physical and psychological examinations or tests. Examples include studies involving ECGs, DEXA scans, anthropometrics, exercise testing in healthy volunteers, physical exams, oral or intravenous glucose tolerance tests, indirect calorimetry, MRI scans, venipuncture, or routine psychological testing; non-interventional studies (e.g., surveys/questionnaires of a non-sensitive nature or observations of behavior or nutrition); or Category I radiation risk (HE (mrem) < 500 mrem and organ limit of HT < 150/WT).

Low Risk - Involves a minor increase over minimal risk. The study involves risks reasonably commensurate with those inherent in actual or expected physiological, psychological, social, or educational situations. Examples include healthy volunteers performing well-described low-risk research procedures such as an intravenous infusion, or euglycemic clamp; Category I radiation risk (HE (mrem) < 500 mrem and organ limit of HT < 150/WT); studies that otherwise meet criteria for minimal risk but involve special populations (e.g. mentally incapacitated); studies that involve invasive procedures or sensitive information; or post-marketing studies (phase IV drug/device studies as defined by the FDA).

Moderate Risk - Risks are recognized as being greater than low, but are not considered as serious as high risk, and their surveillance and protections are adequate to identify adverse events promptly and keep their effects minimal. Risks are considered reasonable in relation to anticipated benefits to research participants and the importance of the knowledge that may reasonably be expected to result from the study. Examples include placebo-controlled studies involving study participants with a recognized disease; studies involving HIV/AIDS, hepatitis, or cancer non-critical patients on investigational treatments, studies where there is substantial risk (greater than 5% of participants experiencing SAEs) related to the underlying condition of the research participants; studies involving seriously ill patients; phase I or II studies where safety is already documented with human data; industry-sponsored phase III clinical trials; Category II radiation risk (HE (mrem) 500 < HE < 5000 mrem or organ limit of 150/ WT < HT < 750/WT) or PET scanning; or low risk studies involving vulnerable populations (e.g. subjects with impaired capacity to give informed consent).

High Risk - Involves greater-than-low risk without prospect of direct benefit to research participants, but the study is likely to yield generalizable knowledge about the disorder or condition studied. In situations where the prospect of direct benefit to the study participant exists, the risks associated with study procedures are considered substantial. Examples include interventions or invasive procedures that involve substantial risk (may result in permanent physical and/or mental changes, hospitalization, and/or death); blinded Phase I and II trials; investigator-initiated IND trials or implantation of a device with an IDE; studies involving the manufacturing of agents on campus or use of a chemical/drug/device for which there are little or no human toxicology data; gene transfer studies or research involving recombinant DNA; Category III radiation risk (HE (mrem) > 5000 mrem or organ limit of HT > 750/WT); investigator-initiated phase III or multi-center clinical trials; or studies where consent is waived such as in emergency circumstances or in populations unable to give informed consent (e.g., mentally incapacitated).

Other factors can influence the risk assignment and must be taken into consideration. These include ethnic considerations, psychological impact, or social implications of a protocol, experience of the research team, potential for conflicts of interest, and the potential for invasion of privacy or breach of confidentiality. The involvement of vulnerable populations such as children, pregnant women, the elderly, psychologically or neurologically impaired individuals, or prisoners will be assessed for participation by the level of risk and not solely on their specific vulnerability category.

It is also important to note that according to the November 18, 2002 memorandum from NCRR, any “protocol that places participants at significant risk” requires a formally constituted Data and Safety Monitoring Board (DSMB). Complying with this directive, the OUHSC GCRC requires a DSMB for those protocols that are phase III, double blind, randomized multi-center trials or are deemed by the GCRC Advisory Committee (GAC) to involve moderate or greater risk.

Minimal, low and moderate risk protocols will be reviewed annually by the GAC unless there are specific factors that suggest the need for more frequent review.High risk protocols may be reviewed more frequently as designated by the GAC.