By Denny Smith, Contributing Writer
Interviewing Charles Allison, MD, Elise Levine, and Carla J. Siegfried, MD EyeNet
For many health care providers, institutional review boards (IRBs) may seem like ubiquitous wallpaper in the bureaucracy of medicine. But beneath all the paperwork are purposes both powerful and profound—and the reach of IRBs may extend further than you realize. Here is a quick primer on when you may need IRB approval and what that might involve.
The Role and Reach of IRBs
“The job of an IRB is twofold: to protect the patient and protect the integrity of the information gathered in research,” said Carla J. Siegfried, MD, of Washington University in St. Louis. In the United States, IRBs are regulated by the FDA, an agency that has been accused of both laxity and overzealousness. Generally, however, its record of oversight has made the United States arguably the safest country in the world for drug testing and approval. IRBs then extend that FDA oversight to the smallest community-based practice as well as the world’s most powerful research institutions.
When Is IRB Approval Required?
“In any context that can plausibly be regarded as research, there really is not a lot of wiggle room in what is and what is not subject to IRB approval,” said Elise Levine, who serves as both practice administrator and director of clinical research at a practice in Mission Hills, Calif. Pharmaceutical manufacturers who approach physicians to function as investigators for an investigational new drug (IND) protocol will already have secured the FDA’s approval to move forward with clinical trials. But all actions related to physician- investigator recruitment of patients require IRB approval, said Ms. Levine.
Are you performing research? “The whole concept of research is to test a hypothesis, so it can add to a body of knowledge,” said Dr. Siegfried. “It doesn’t have to be [about] a drug or procedure to qualify as research. And it doesn’t matter whether the research is retrospective or prospective. Even observation of a patient is research that needs prior approval if it is explicitly intended to influence medical practice and is intended to be entered into the public record and applied prospectively. Always question whether you are performing ‘research.’” Don’t try to skip the IRB process or do it after the fact. Journals require IRB approval before a study is started as qualification for publication.
When don’t you need IRB approval? Dr. Siegfried described commonsense situations in which IRB oversight is not warranted. “If you are simply going to present a case at a private presentation, and you honor the patient’s privacy and do not plan for the case to become generalizable knowledge, then the task of seeking IRB attention is not necessary.”
Three types of review status. Dr. Siegfried outlined the three types of IRB review status:
- Full review, intended for any research that will exceed minimal risk to the patient, such as offering a new drug or device for treatment.
- Expedited review, for research considered to pose little risk, such as noninvasive studies, or chart reviews and observational studies.
- Exempt status, for studies that pose no risk and offer no identifying data on patients; examples are instructional assessments or reviews of data.
The level of risk for the patient is the key factor, said Dr. Siegfried. “Any prospective study regarded as posing some risk is going to command careful IRB scrutiny. Where there is minimal risk, you may earn an expedited review. And if there is really no risk to the patient, such as in a retrospective review, you may be exempt
from an IRB review.”
What You Can Expect
A sponsor’s study. Most new drug protocols are initiated by a pharmaceutical manufacturer and approved by the FDA; these will automatically come with all the necessary documentation templates for the study site.
“Usually, if you are participating in a sponsor-initiated study, the sponsor, such as a pharmaceutical or device company, does all of the legwork for the IRB submission process. The only thing you are doing is filling out a boilerplate information sheet that gives background about your practice, shows your competency to complete the study, and your ability to follow the rules of both the protocol and good clinical practice. In this case, the IRB application is a very straightforward process, if the clinician is prepared with basic information, said Ms. Levine. “One should have ready the doctor’s license, the CVs of all staff who will be working on the study, a history of previous studies with enrollment goals and measurements, and general information about the office.”
Your own study. If you are creating your own study, “you must write the protocol, and the IRB then makes sure that it is up to snuff,” she said. There also are many rules to follow when you create the consent form, which must be accompanied by a copy of the patient’s bill of rights, said Charles Allison, MD.
What are the staffing requirements? As with everything in medical practice, staffing requirements become relevant sooner rather than later, Ms. Levine said. “For handling an IRB submission, the practice manager should be well aware of the requirements on the IRB application. Knowing those requirements and how to meet them can be a delegated task, but usually there are questions that are best left for the practice coordinator or manager who has decision-making authority.”
In cases involving large studies, Ms. Levine said it might require one person just to manage the paperwork, and that person will need at least some familiarity with the principles of research. “You have to make sure everyone involved in human trials comprehends general concepts in research. One easy way to do that is to enroll the staff in an online class on research.” Such training should include protecting patients’ rights, added Dr. Allison. “This is usually required by the IRB.”
Take care with your recruitment. “The most common mistake is after the submission process, when you are beginning to recruit participants,” said Ms. Levine. “Advertising and solicitation for study patients is highly regulated to ensure safety for patients and no undue coercion. Any and all recruitment tactics must be approved by the sponsor and also the IRB. Some practices post advertisements on Craigslist, on their website, and on their Facebook page, or go out in the community to recruit—all without having the materials approved. These are no-no’s.”
Ongoing reporting to the IRB. The relationship of an ophthalmic practice to an IRB does not end with approval to recruit patients to participate in a study, both Dr. Siegfried and Ms. Levine said. Periodic reports by the physician-investigator must be sent to the IRB, usually quarterly, to update enrollment figures and to present both therapeutic and adverse events, as well as any changes to the protocol. In this way, patients get ongoing protection, and the investigator is safeguarded from proceeding in a dangerous direction. This information is also used to look at overall enrollment and progress for a study. Those who enroll too few patients, as well as those who enroll much higher than the norm, are scrutinized to ensure they are following all of the guidelines for the study.
Be quick to report adverse events and departures from the protocol. Any deviation from the protocol must be reported within a specified period of time. “In addition, any serious adverse event must be reported immediately to both the IRB and the sponsor,” said Ms. Levine. “You must have some mechanism for capturing patients who are not responding to the treatment or who are being adversely affected by the treatment,” added Dr. Siegfried.
Inside an IRB
An IRB member’s perspective. The work of IRB members can be quite taxing, according to Charles Allison, MD, who is the longtime chairman of the IRB at St. Mary’s Medical Center in San Francisco and who maintains a private practice nearby.
A rewarding endeavor. Dr. Allison is an internal medicine physician, not an ophthalmologist, but in considering new study proposals month after month as chairman of the IRB, he keeps abreast of important developments in ophthalmic medicine. “I have benefited tremendously from learning about research outside my own practice. The IRB can be an important vehicle for learning and not just for regulation.”
An increasingly time-consuming enterprise.Due to the format required by the FDA, the protocols for trials have become extremely verbose over the years, with lots of repetition, said Dr. Allison. “The actual material in them might not be that complicated, but they run to a lot of pages and are time-consuming to read.”
Another activity that takes a lot of time, at least for some IRB members, is reviewing adverse events, especially for protocols that include complex treatments like cancer chemotherapy drugs, he said.
Charles Allison, MD, practices internal medicine at Mercy Doctors Medical Group and chairs the IRB at St. Mary’s Medical Center; both are in San Francisco. Financial disclosure: None.
Elise Levine is a practice administrator and director of clinical research at the North Valley Eye Medical Group in Mission Hills, Calif. She was 2012 chairwoman of the AAOE. Financial disclosure: None.
Carla J. Siegfried, MD, is professor of ophthalmology and visual sciences at Washington University in St. Louis, as well as a member of the Academy Ethics Committee. Financial disclosure: Is an equity owner in HDI and receives grant support from Alcon and the NEI.