Expedited reviews call for same due diligence

OHRP official offers guidance on process

IRB members and others in the research community sometimes have misconceptions about the use of the expedited review process, including the idea that an expedited review is different from a review by the full IRB.

"The standards of review are unchanged," says Glen Drew, MS, JD, health policy analyst with the Office for Human Research Protections (OHRP) in Rockville, MD.

The expedited review process is not intended to be seen as IRB-light, he says.

"The study needs to have risks minimized and risks balanced with potential benefits and informed consent," Drew explains. "The only difference is that the review can be conducted by one or more members of the IRB without the requirement for there to be a convened meeting of the IRB."

An expedited review only can occur with a study that presents with no more than minimum risk to subjects and which involves only the procedures included in the list of categories that are qualified for the expedited review, he states.

Studies do not qualify for expedited review if the study could result in the identification of subjects whose participation would place that at risk for criminal or civil liability. Likewise, studies cannot be stigmatizing or damaging to the reputation, and the expedited review process may not be used for classified research involving human subjects. Such research would require a full board review, Drew says.

The first seven expedited review categories apply to both initial reviews and continuing reviews. Then there are two more categories that apply only for continuing review of research previously approved.

The nine categories are as follows:

• Category 1 - Clinical studies of drugs and medical devices only when two conditions are met. Condition A pertains to research on drugs for which an investigational new drug (IND) application is not required, Drew says.

"Research on marketed drugs that increases risk or decreases the acceptability of risk is not eligible for expedited review," he explains.

For example, if a study involves a drug that does not require an IND, but which will be investigated with a different route of administration, such as being administered orally instead of intravenously, would not be eligible for Category 1 because it would alter the risks or change the balance of risks, Drew says.

Condition B is for medical devices for which an investigational device exemption is not required or for medical devices that have been approved for marketing and are used in accordance with their approved labeling.

• Category 2 - Blood samples, heel stick, venipuncture, hand stick of health adults. With this expedited review category, subjects can have up to 550 mL drawn in an eight-week period, but they cannot have blood collected more than twice a week, even if these are small amounts. For other adults, as well as for pregnant women and children, investigators have to work in consideration of their age, height, health, and weight. The method of blood collecting and frequency will have an upper limit of not exceeding the lesser of 50 mL or 3 mL/kg in an eight-week period and not have these collected more than twice a week, Drew says.

"So if you’re doing a study that includes collecting blood from an infant three times a week, the study can be done, but it has to be reviewed by the convened IRB," he explains. "There is a 110-pound minimum for healthy, nonpregnant adults."

Also, if a study includes one of the categories of collection of blood samples, but also includes an X-ray of some part of the body, it would not qualify for exemption because it would include procedures that quality and some that do not qualify, Drew says.

• Category 3 - Prospective collection of biological specimens for research purposes by noninvasive means. These specimens may include hair, nail clippings, deciduous teeth at the time of exfoliation and if patient care indicates need for extraction, and external secretions including sweat, he says.

Amniotic fluid could be obtained at the time of the rupture of the membrane, during labor, but at any other time it would require full board review, Drew adds.

The collection of hair and nail clippings must be done in a nondisfiguring manner. For example, if the study included the cut of a fingernail past the section that has grown out, then it would not be eligible for Category 3, he says.

• Category 4 - Collection of data through noninvasive procedures, not including anesthesia. This category specifically excludes X-rays and microwaves, as well as excluding medical devices that have not been approved for marketing and studies that involve studying safety and efficacy of devices, Drew says.

The category does apply to physical sensors applied to the surface of the body or at a distance, and it does not involve the input of energy into the body or invading a person’s privacy, he says.

"Weighing a subject or testing for sensory acuity, doing a vision examination, and looking down the room at a classic eye chart would qualify for expedited review," Drew says.

Other tests that would qualify include electrocardiography and electroencephalography, ultrasound, diagnostic infrared imaging, thermography, detection of naturally occurring radioactivity, and electroretinography, he notes.

Also included are moderate exercise and muscular strength testing, body composition assessment, and flexibility testing.

"I would think that moderate exercise in patients with congestive heart failure would require a full review if they’re done for research purposes and not to assess the individual’s need for medical care," Drew says.

• Category 5 - Research involving materials, data, records, documents, or specimens that will or have been collected for nonresearch purposes, such as medical treatment or diagnosis. "This refers only to research that is not exempt," he says.

An example for this category would be if patients were given X-rays for diagnostic purposes and a research proposal would look at those X-rays, Drew says.

"You can do an expedited review procedure on a study of X-rays taken for treatment or diagnostic purposes," he adds.

• Category 6 - A collection of data from voice, video, or imaging recordings made for research purposes. "In essence, if these are made for nonresearch purposes, you could do an expedited review under Category 5 or have it considered exempt," Drew explains. "If it’s just for research, like a study on accents in the United States or some stress analysis of voices of people in mock job interviews, then it’s a Category 6."

• Category 7 - Research on individual or group characteristics or behavior. This includes, but is not limited to, research on perception, motivation, identity, language, communication, cultural beliefs or practices, and social behavior.

This also could include research employing survey interviews, oral history, focus groups, human factors, or quality assurance methodologies, Drew says.

"Some of this research may be exempt from Health and Human Services regulations, and this research list only applies to research that is not exempt," he says.

An example of a Category 7 expedited review study would be death rituals of a subculture, Drew says.

Category 7 might not be used as much as it should be, he notes.

"Certainly there are institutions that don’t utilize expedited review procedures at all for any research, whether it would qualify or not," Drew says. "They made an institutional decision."

• Category 8 - Research previously approved by a convened IRB. This category applies to research that was not reviewed by expedited procedures at initial or continuing reviews, he says.

The first part is for research that is permanently closed to enrollment of new subjects and all subjects have completed research interventions, Drew says.

"Research remains active only for long-term follow-up of subjects," he says. "That’s one type that would qualify for expedited continuing review, even if reviewed by a convened IRB previously."

Category 8 is the only expedited review category where research that is of greater than minimal risk can be reviewed under expedited review procedures, Drew says.

And the second part applies to studies in which no subjects have been enrolled and no additional risks have been identified, he says.

"These are studies in which you have a study open, but no subject presents for over a year, and there is no one exposed to risk and no new risk has been identified," Drew says.

The third part applies to research activities that are limited to data analysis, he adds.

• Category 9 - Research of relevance to the Food and Drug Administration. This category applies to the continuing review of research that is not the investigation of a new drug or device, but which does not apply to the other categories, Drew says.

"This is a study where for some reason it did not fall within the prior categories and had been required to be reviewed by the convened IRB, but in that review the IRB found that the research was of no greater than minimal risk, and there’s been no change in risk profile," he explains. "This can occur only after there has been a convened meeting at a previous review."