Accurate extrapolation of actual-use data into broader consumer settings will be a defining measure of success for switching chronic disease drugs in the future, according to FDA Office of Nonprescription Products Director Charles Ganley, MD.

"Information selection is critical, and understanding why someone makes an incorrect decision is essential," Ganley said during the CHPA Regulatory & Scientific Conference in Washington, D.C. May 6.

Ganley pointed to the recent statin switch meeting as an example of determining the "real world" impact if a cholesterol-lowering drug such as Merck's Mevacor (20 mg lovastatin) were switched OTC.

The Nonprescription Drugs and Endocrinologic & Metabolic Drugs Advisory Committees rejected the switch in January (¹ Also see "Mevacor Daily Regimen Compliance Questioned By FDA Committees" - Pink Sheet, 17 January, 2005., p. 5).

Mevacor OTC Actual-Use Study Lessons

Even though three-quarters of actual-use study participants correctly self-selected, two-thirds required help from a physician, Ganley noted. Moreover, of the participants who self-selected on their own, only half made the correct choice.

"I think that one of the things that we're grappling with is how do you carry this data over into the real world, so we [should] focus on the consumer who did not use a physician because there is a significant portion of the population who do not have access to a physician," he said.

"Even if a drug is deemed safe," Ganley continued, "failure to self-select correctly by a significant portion of users may be unacceptable. That's the essence of what the committee was saying."

Drugs vs. Categories: What's The Difference?

Ganley put challenges for future chronic condition switches into two categories: drug-related hurdles and drug category-related hurdles.

"For the most part, and in the January meeting, the drug made it over a lot of those [drug-related] hurdles. But it didn't make it over the category hurdles, which gets back to the consumer behavior and the self-selection process."

Ganley said FDA would have to evaluate more carefully incorrect self-selectors, who read and understood the label, yet still made the wrong choice.

"In FDA, there are going to be folks that would have a problem with that," he noted, adding, "I personally don't, but I sort of looked at it that people make a lot of choices."

At the same time, consumers that self-selected incorrectly for OTC Mevacor would be at low risk for serious adverse events, according to Ganley.

"Those people are going to have a lowering of their cholesterol. Their risks for an event may have been low to begin with and the absolute benefit they're going to be getting is fairly low, but if they understand that and they understand the risks, that was a decision they made."

Ganley suggested more open-ended questions as an improvement over study questionnaires that use yes-and-no questions and lead to routine answers.

He cited, for example, consumers carrying a less than 1% risk for a cardiovascular event over 10 years that choose to take a cholesterol-lowering drug. "They may have had a logic there that you would have heard and said, 'I can understand that, I can live with that.' And it may be fine, but you have to collect that information."

Topical Corticosteroids

Ganley highlighted the recent NDAC/Dermatologic Drugs advisory committee meeting on topical corticosteroids as another case where the panel needed more consumer-use data for an Rx-to-OTC switch (² Also see "NDAC Approach To OTC Switches Highlighted At Corticosteroid Meeting" - Pink Sheet, 28 March, 2005., p. 5).

The number of subjects requested by the joint committee to participate in an OTC safety study (1,000) far exceeded the number used for Rx approval (30 to 50), Ganley noted, suggesting the conservative stance could be the result of COX-2 inhibitor safety woes.

"These are products that have been marketed for more than five years, and you would think we would know some of the side effects associated with it," he said.

"I think one of the issues [at the topical steroid meeting] is that the physicians did not have confidence that consumers would behave like they should, and that they needed someone to hold their hand through the process here," Ganley suggested.

He questioned whether FDA was unsuccessful in communicating what it was looking for from the joint panel or the agency did not have the appropriate mechanisms in place to accurately analyze consumer use.

"I don't know if it's a failure on our part that we did not emphasize that more at the meeting, or that...it just reflects that we don't have the tools to understand why people don't use [topical steroids] correctly, and how do we make someone use it correctly."

Ganley indicated the OTC unit's transition from a division to an office will allow the opportunity to improve understanding of consumer behavior.

"I think we all recognize that is critically important. We have to build that expertise," he stated. FDA is "committed to expend[ing] resources on it because...we have to understand the data, be comfortable with the data and endorse the data internally before we present it to advisory committees."

Switches: Approach With Caution

Ganley cited long-held views by advisory experts on consumer decision-making as a possible long-term challenge to switches.

"There's some failure on our part to not recognize that these biases that [the Dermatologic committee members] may have had about consumer behavior, consumers using the products as directed, was so ingrained in there. And we have nothing to offer them for how we can overcome that."

Former NDAC chair Eric Brass, MD/PhD, UCLA School of Medicine, agreed that Rx switch advisory panels approach potential OTC candidates with extra caution.

"The assumption is that there are more axes for communication and intervention than there would be without the management paradigm. At a minimum, the Rx almost always guarantees that the individual has access to a healthcare professional if they needed to."

By comparison, the OTC "self-management paradigm is modeled under the worst-case scenario."

FDA’s Ganley Puts Rx Switch Studies In “Real World” Context

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