FDA ruling may increase clinical trials
FDA ruling may increase clinical trials
Manufacturers can charge for drugs now
The Food and Drug Administration's (FDA's) new final rule on expanded access to investigational drugs has the potential to result in increasing clinical trials through its advocacy of intermediate-size patient populations.
Historically, one patient asks for access to an investigational drug, the request is sent to the FDA, and a treatment protocol would be returned if the request is approved. There was no data collection to see if multiple patients were using this unapproved drug, says LaDale K. George, JD, a partner with Neal Gerber & Eisenberg in Chicago, IL.
This changes under the FDA's final rule, published Aug. 13, 2009, in the Federal Register, and titled, "Expanded Access to Investigational Drugs for Treatment Use."1
The final rule, which is effective Oct. 13, 2009, is the result of the Food and Drug Administration Modernization Act of 1997. The FDA proposed the rule in December, 2006.
"I'm encouraged that the FDA in its regulations has permitted the FDA to request sponsors to amend or create new INDs, protocols where the FDA has received numerous individual requests for expanded access," George says.
"So if the FDA starts to see where they're getting individual expanded access requests from 35 people they can go back to the sponsor and say, 'We think you might want to consider a clinical trial for this or expand it to this population,'" he explains.
Calling these small groups intermediate-size patient populations, the FDA defines these as groups that are smaller than the typical cohort of a treatment IND or treatment protocol.
"The FDA will help sponsors recognize they may have a more sizable pool of patients than they first realized," George says. "And given the level of electronic connectivity and communication among our patient community, it could be they encourage meaningful changes in the world of drugs."
For example, people who regularly visit an online patient advocacy chat room might exchange information about a treatment protocol that could help them with their disease, he suggests.
"One patient might say, 'I'd like anyone out there who has not met clinical trial protocol criteria to join me on this,'" George explains. "And then you're changing the direction of medicine, and that's exciting."
This type of change depends on public reaction to the final rule on expanded access.
But at the very least, the final rule provides clarity to patients and physicians about how they may access experimental therapies, George says.
Balancing access, protection
Public comments made to the proposed rule showed a wide range of concerns, including those from people who feel the rule is too liberal and those from people who feel it's too restrictive, says Mark S. Schreiner, MD, associate professor of anesthesia in pediatrics at the University of Pennsylvania in Philadelphia, PA. Schreiner also is the chair of the Committee for the Protection of Human Subjects (IRB) at The Children's Hospital of Philadelphia.
"They tried to balance the needs for greater access with the needs for appropriate patient protection," Schreiner adds.
For example, some comments expressed concern that there might be an inadequate supply of some investigational drug to meet the demand for its use in expanded access, and this would make it impossible to provide it to everyone who seeks it. As such, one comment said that expanded access of an investigational drug should be allowed only when there was adequate supply.
But the FDA disagreed, saying that expanded access programs could proceed even when supplies are limited. There are mechanisms that have previously been used to fairly allocate limited drug supply, and these include lotteries.
The final rule also considers expanded access programs to include studies without scientific goals, Schreiner says.
"A lot of things that were open label trials now are considered expanded access programs," he says. "These expanded access programs are for treatment, not for scientific goals to answer efficacy questions."
Efficacy questions should be answered in the context of clinical trials, Schreiner adds.
"They have provisions in the rule to allow for the treatment of an individual patient, and they also have rules for intermediate-size patient populations," he says.
Also, the FDA discusses instances in which drugs are not being developed because the population that would need the treatment is too small, Schreiner notes.
"Or maybe a drug is being developed, but there might be patients who can't participate in the study because they don't live close enough to the trial site, or maybe they're too sick to meet entry criteria for the study," he explains. "The FDA took these types of situations and explained how an expanded access program could be set up."
Burden of submissions
One major drawback to the final rule is that it will require burdensome administrative responsibilities for submission, and this is likely to limit physicians' willingness to access therapies in this way, says George.
"The submission requires that you have a description of the facility where the drugs are manufactured, the chemistry, and pharmacology information," George explains. "This wasn't previously required of a physician seeking a treatment IND."
"The doctor might simply say, 'I have no way of accessing this information other than going to the sponsor, and the sponsor has chosen for some reason to not grant you access directly,'" George says. "It creates a stalemate, and we might be right back where we are today: we've gone forward, but we haven't moved."
The FDA published a second final rule that might give drug companies enough incentive to make it easy for patients to have expanded access to investigational drugs. This rule, titled, "Charging for Investigational Drugs Under an Investigational New Drug Application," also was published in the Federal Register on Aug. 13, 2009.2
The rule shows how manufacturers can charge for investigational drugs.
"I think the FDA has done a very good job of providing clarity around charging in both clinical trials, as well as for expanded access, and the final rule goes beyond what was previously in the regulations," George says. "I'm hats off and happy with that."
"I think the ability for the sponsor to charge for the direct cost associated with granting expanded access, including the cost for monitoring and complying with IND reporting requirements should increase the willingness of sponsors to allow expanded participation," he adds. "They'll send them the information they need and a bill along with it."
Manufacturers can charge for these investigational drugs, but there are no requirements that third party payers have to cover them.
"People said the FDA should make it clear that insurance companies can pay for these, but it's not the FDA's job to do that," Schreiner says. "We hope insurance companies might cover it, but it's not guaranteed that they will, and it's not the drug company's problem."
Since it can take one to two years for an investigational drug that has shown efficacy and safety to complete its FDA application process and receive approval, expanded access programs can offer patients and clinicians some much needed help during the interim period.
"So this rule makes it possible for companies to charge for these drugs during the interim," Schreiner says.
The final rule also broadens the criteria for being granted expanded access by using the term "serious disease or condition."1
"It broadens the scope of the conditions," Schreiner says.
By referring to a serious disease or condition, as well to an immediately life-threatening disease or condition, the FDA has broadened the rule's reach.
"For example, there was a question about epilepsy and whether that would be included," Schreiner explains. "And the FDA said people who go into status epilepticus have a 6% mortality rate, and this would be considered an immediately life-threatening condition."
By including serious diseases that substantially impact day-to-day functions, the FDA is including chronic illnesses for which there are no strong treatments, George says.
"You may see the granting of expanded access in these cases," he adds. "For those who have a chronic illness for which there is limited or no treatment, they might find investigators out there who are willing to grant expanded access opportunities for them."
This final rule potentially could usher in an exciting time for medical treatment and research, George says.
"The current patient community has become so information savvy they will encourage physicians to look at innovative ways to address their treatment limitations," George says. "And those physicians in turn will put pressure on industry to make medications available through this new expanded access."
References
- Expanded access to investigational drugs for treatment use. Fed Reg. 2009;74(155):40900-40955.
- Charging for investigational drugs under an investigational new drug application. Fed Reg. 2009;74(155):40872-40900.
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