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View IRB process as a help, not an obstacle to research
Informed consent is a process — not a form
Investigators and research staff often take a sour view of the IRB process, thinking of it as a burdensome hurdle to starting a clinical trial.
It would be more productive to view the IRB review process as a way to clarify the risks and benefits of a study and to improve the informed consent process, experts note.
Ideally, IRB staff will be trained to triage protocol applications and work with investigators and clinical trial staff when an application needs improvement, says Dawn Dowling, BS, CIP, compliance administrator at Carnegie Mellon University in Pittsburgh, PA.
"They can make sure the investigators give them all of the necessary information and have it written clearly so there won't be any questions," Dowling says. "They can be an advocate for the IRB and understand what a study is about."
This ideal world scenario isn't always possible because of the often understaffed IRB office environment and the increasing paper burden placed on IRB office employees, says John Chinn, MBA, compliance director at Carnegie Melton University. Both Chinn and Dowling spoke about the IRB application process at the Northeast Section of the Society of Research Administrators International Conference in Newport, RI, held April 21-25, 2007.
"Some institutions have six IRBs, and each may review three or four new protocols a month, plus dozens of modifications and renewals," Chinn says. "And if you have a staff of four IRB administrators, it's really tough for the administrators to read entire protocols and try to figure out what the investigator is missing in it."
IRB administrators should do their best to help investigators and clinical trial staff complete the application, and the form should not be so burdensome that it discourages investigators from going to the IRB, making it difficult to get through the process, Chinn adds.
"So, if each institution could balance the risks that it takes when determining what information is absolutely necessary for an IRB to make an informed or good review of the clinical trial protocol or IRB protocol, and then balance that with the burden of the documents to the investigator, that would be helpful," Chinn says.
Clinical trial administrators and investigators can improve their own IRB applications by following these tips:
• Understand what IRB wants from informed consent: "When you put together an IRB application, what you need to do first of all is come up with a lay abstract that everybody understands," Chinn advises.
"It doesn't have to be written at sixth or eighth grade level, but it should be in a format that someone with that level of education could understand," Chinn says.
Pharmaceutical companies often give investigators a sample consent form with its own language, explaining what the study is about and what the risks and benefits are, Chinn notes.
"Many investigators are short-staffed, and they don't have a whole lot of time to reinvent the wheel, so they cut and paste examples from the pharmaceutical company's form and submit that to the IRB," Chinn says.
"But the IRB reviews it and looks at the informed consent form from their own institutional culture," he says. "And there may be language they find unacceptable to that particular culture or institution."
For example, some institutions require stricter language about the disclosure of pregnancy results in a study in which participants cannot be pregnant and are tested regularly, Chinn explains.
"If the investigator is working with minors, the IRB might require that the parents be informed about the results of the pregnancy test," he adds
It's also crucial that informed consent forms include clear language on who will pay for the various procedures included in the clinical trial, Chinn says.
"Because of the current health care environment and the insurance company paying for extra procedures, it's important the subject realize he or she may not be responsible for any of the additional costs of research tests," he says.
For instance, if the study was about asthma, and three chest x-rays were required while a subject was taking an asthma drug, it might be that the patient's insurer will only pay for the one X-ray which is the standard care, Chinn explains.
"So, someone has to be responsible for the other two X-rays, and it's important that the consent form tells the subject who the person is that will pay for the additional chest X-rays," Chinn adds.
"For clinical trial research, I believe the risks and benefits usually are adequately disclosed, but there's often confusion about clinical standard of care versus research," he says.
Depending on the subject population, clinical trial administrators and investigators need to make certain the risks and benefits of a trial are equally distributed, Dowling says.
"You need to know that informed consent starts at the start of the study, during subject recruitment," Dowling adds. "You need to know everything a participant would see and do, including recruitment materials and debriefing."
Make certain that the person who is signing the informed consent is legally able to sign it and is able to understand what they are going to do, Dowling says.
These institutional and cultural considerations challenge the investigator to understand the protocol more fully so they can rewrite the informed consent form in a way that will satisfy the IRB's concerns, Chinn adds.
Also, investigators should keep in mind that the informed consent process doesn't stop when the patient signs the form and leaves, Dowling says.
"Informed consent is a process that continues throughout the entire study, maybe for years and years," Dowling says. "Informed consent can be taken away at any time."
Participants need to be informed that they can withdraw from a study at any time, for any reason, she adds.
When Dowling audits a clinical trial, she'll ask the investigator to walk her through the informed consent process.
"I say, 'Treat me like a participant,'" Dowling says. "The informed consent process starts with either a flier or email or phone call."
Investigators need to be careful to not make promises they can't keep and to let subjects know if they can't answer a question, she notes.
"Don't give them a false answer," Dowling says.
"I think the people who are going to be talking to subjects, the nurses, researchers, and doctors, need to understand the study and make sure they address all of the patient's concerns appropriately and accurately," Dowling says.
• Thoroughly plan statistical sampling: Part of the Belmont Principle involves the benefits to society and respect for the people participating in research, Chinn notes.
"You don't want to use more subjects than you really need, but if you don't get enough subjects to result in significant power in the study, then you've wasted all of the subjects and these resources," Chinn explains. "So that's why the IRB looks at the number of subjects you plan to enroll."
It's important for investigators to show clinical significance in their protocols, and this work should be done right before the protocol is submitted for IRB review, he adds.
If there is a problem with the protocol's enrollment projection, then the IRB might say, "We don't believe you have significant power to find your answer," Chinn says.
"And they'll have the investigator go back and recalculate and suggest a different number," he says.
IRBs have different resources and offer different services, but at least one institution Chinn knows there is a statistician who works with the IRB, and this person helps investigators determine the correct sample size for their research, he adds.
With pharmaceutical company-sponsored trials, a statistician typically has helped the proposed study determine the optimal number of participants, Chinn says.
Typically, there will be no change in the number of participants during the course of a trial, unless the trial is going very well at one particular site and the sponsor organization asks that site to enroll more participants, Chinn notes.
"Where you find an increase in numbers is when the site has been so successful that they've reached their limit of their initial request for recruitment," Chinn says. "And the pharmaceutical company says, 'You're doing so great, will you please continue recruiting, and so the investigator will submit an IRB application to recruit additional subjects."
• Provide IRB and ethics training to staff: Training for principal investigators and clinical trial staff is very important, Dowling says.
"You need to make sure researchers and anyone who is going to interact with human subjects or human subject data is trained," Dowling says. "This can be on-line or through internal education courses."
Even the people who do nothing more personal than analyze the data need to understand that it's human subjects data, and they need to know how to treat it, Dowling adds.
Clinical trial staff need information about why the IRB asks for particular documents, she explains.
It's not enough to know what's required by the IRB, the staff should understand why it's important to the IRB, Dowling adds.
For example, investigators need to know why the IRB pays detailed attention to the language in the informed consent form, Chinn says.
"We tell investigators that this is a teaching opportunity," he explains. "They're teaching participants about what kind of research they're doing."