Pragmatic research is often deemed to be minimal risk, and for no more than minimal risk research, IRBs can approve a waiver or an alteration of consent. A waiver means no consent is required. An alteration is consent in which some of the elements of full regulatory consent (described previously in this chapter) are altered. We describe alteration of consent in more detail later in this chapter.

According to the Common Rule an IRB may approve a consent procedure which does not include, or which alters, some or all of the basic elements of informed consent, or it may waive the requirement to obtain informed consent, provided the IRB finds and documents that:

• The research involves no more than minimal risk to the subjects (described in more detail below);
• The research could not practicably be carried out without the requested waiver or alteration (described in more detail below);
• If the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format;
• The waiver or alteration will not adversely affect the rights and welfare of the subjects; and
• Whenever appropriate, the subjects or legally authorized representatives will be provided with additional pertinent information after participation.

Minimal Risk Research

A study’s IRB makes the determination as to whether the research is minimal risk. The Common Rule defines minimal risk research as follows:

“Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.” §46.102

Note that this definition of minimal risk only applies to the additional risk of the research, as opposed to the underlying risk of the clinical disease or disorder. For example, consider a study that requires values from a cardiac catheterization. If the cardiac catheterization was performed solely for the research (additional risk), the research would be greater than minimal risk, but if the catheterization was done as a part of the routine care, the research could be considered minimal risk because using the data for research does not add any additional risk. In some research, the additional risks are largely informational—the risk of harm is not physical at all—but comes from the potential for inappropriate disclosure of private information.

In 1998, the Office for Human Research Protections (OHRP) generated a list of categories of research that may be reviewed through an expedited review procedure. The list provides useful examples of minimal risk research.

In pragmatic trials that compare different types of usual care, additional risk would likely be limited to informational risk. But in pragmatic studies that compare usual care to usual care with an additional procedure (A versus A+), there may be additional risks to consider.

Practicability

The Secretary’s Advisory Committee on Human Research Protections (SACHRP) drafted a letter that can be used as guidance to aid IRBs in determining whether research could not practicably be carried out without a waiver or alteration of consent (OHRP 2008). The key considerations include:

• Whether the scientific validity would be compromised if consent was required. For example, if the sample size required is extremely large or if the subjects to be included are no longer followed or may be lost to follow-up.
• Whether consent raises ethical concerns, such as creating additional threats to privacy or a threat of psychological, social, or other harm by contacting individuals or families.

Note that SACHRP states that there must be “a scientifically and ethically justifiable rationale why the research could not be conducted with a population from whom consent can be obtained” and the “practicability should not be determined solely by considerations of convenience, cost, or speed.” (OHRP 2008)

Case Example for Waiver of Consent: Lumbar Imaging with Reporting of Epidemiology (LIRE)

Lumbar Imaging with Reporting of Epidemiology (LIRE), an NIH Collaboratory Trial, was designed to test whether inserting epidemiological evidence (essentially representing the prevalence data for common imaging findings in individuals without back pain) in lumbar spine imaging reports will reduce subsequent diagnostic and therapeutic interventions, including cross-sectional imaging (MR/CT), opioid prescriptions, spinal injections, and surgery (Jarvik et al. 2020). As part of their justification for a waiver of patient consent (Ethics and Regulatory Documentation), the investigators cited that the project was minimal risk and would not adversely affect the rights and welfare of the subjects, and that the research could not practicably carried out without a waiver (because there was a large study population of ~250,000 and there was no easily implementable means of obtaining consent as neither the researchers nor the radiologists who read the images had contact with the patients).

Furthermore, the investigators explain:

“By informing primary care providers and patients of the study, we risk invalidating the results. If providers and patients are aware of the intervention but are allocated to the control group, they may nevertheless change their behavior.

The risk of contacting subjects is greater than the risk of the study procedures. The risk for breach of patient confidentiality increases when subject contact information is maintained for the purposes of contacting patients for their consent. It is our opinion that this increased risk far exceeds the risk to subjects associated with the insertion of epidemiologic data into the radiology report interpreted by their provider.”

Opt In

Opt in refers to when prospective participants are asked (either in writing or orally) if they would like to participate in a research trial, and are included if they say “yes.” When opt in includes all the regulatory elements of consent, it does not require a waiver or alteration. However, opt in is sometimes used in studies with a consent form that does not provide all the required elements. In these cases, it is approvable only when it meets the conditions for waiver/alteration.

Case Example: PPACT Opt In

The goal of the Collaborative Care for Chronic Pain in Primary Care/Pain Program for Active Coping and Training (PPACT) trial was to coordinate and integrate services for helping patients adopt self-management skills for managing chronic pain, limit use of opioid medications, and identify exacerbating factors amenable to treatment that are feasible and sustainable within the primary care setting (Debar et al. 2012; DeBar et al. 2022). Prospective participants were sent a letter explaining the program and indicating that someone from the PPACT team may call to explain more about the program. The letter provided a phone number to call if the individual would prefer no further contact with the investigative team—to opt out. When the PPACT team member discussed the program with a potential participant, the individual was given the opportunity to opt in, which was recorded in EHR.