Merck Mines Mevacor Switch Data To Press FDA On Self-Selection Stance

Purchase decisions in OTC switch self-selection studies offer insight into subjects’ thinking “and how they might act in a real-world pharmacy setting,” Merck tells FDA in response to a draft guidance that says such decisions are driven by cost and are “an unreliable surrogate” for self-selection.

Merck & Co. Inc. joins the chorus of industry stakeholders asserting that purchase decision data reflect more than product cost and are germane to self-selection studies designed for Rx-to-OTC switches.

The comments respond to an FDA draft guidance, published Sept. 16, that says purchase decisions are “an unreliable surrogate for a self-selection decision” because they are mainly affected by cost rather than product label information (Also see "Self-Selection Studies Need Room To Evaluate Purchase Decisions – Expert" - Pink Sheet, 26 Sep, 2011.).

Using a post-hoc analysis of data generated in support of its unsuccessful 2007 attempt to switch Mevacor Daily (lovastatin), the Merck Research Laboratories division says it found many consumers at the purchase decision stage change their choice for reasons other than product cost.

The firm says some consumers reversed previous decisions that the product was right for them, while others overrode their earlier decisions that it would not be appropriate for them based on label indications. According to Merck, the Mevacor data suggest decisions made at the purchase stage contribute valuable information to a study and often are not a factor of cost.

“Both withdrawal and override decisions can give us insight into how the subject is thinking and how they might act in a real-world pharmacy setting,” says Merck in a Nov. 18 comment, which FDA posted online in late December.

While purchase decision questions can be asked following completion of a self-selection assessment, ultimately those data should not weigh on the interpretation of self-selection data, FDA says in the guidance.

SELECT Study Offers Insights

Merck’s Self-Evaluation of Lovastatin to Enhance Cholesterol Treatment study, conducted in 2006, differed from its previous studies on OTC versions of the cholesterol drug by allowing researchers to question subjects on their self-selection decisions and collect open-ended responses (Also see "FDA Advisors Say Greater Insight Needed On Self-Selection Of OTC Statins" - Pink Sheet, 17 Dec, 2007.).

Merck found that only 20% to 25% of subjects who opted to withdraw from self-selection during the purchase decision stage mentioned cost as a factor.

“Data that can clearly help us better understand the way consumers would use a product in the marketplace should not be discounted based on the assumption that cost is usually a major factor in the subject’s decision-making process.”

–Merck & Co.

For many of the 1,499 SELECT subjects, the purchase decision stage offered another opportunity to evaluate whether Mevacor actually was appropriate for their use, according to Merck.

Merck reports that 25% to 30% of subjects initially said the drug was right for them, but then declined to purchase it because they wanted to consult with a physician first. Throughout SELECT, the rate of such withdrawal decisions was much higher than the rate of override decisions – whereby subjects selected against use but subsequently opted to purchase it anyway – the company says.

In reality, the purchase decision may be more tangible to consumers than the self-selection question, and thus can yield contrasting and insightful data, Merck says.

“Data that can clearly help us better understand the way consumers would use a product in the marketplace should not be discounted based on the assumption that cost is usually a major factor in the subject’s decision-making process,” Merck adds.

Selection Decision Needs Context

Eric Brass, a former chairman of FDA’s Nonprescription Drugs Advisory Committee and consultant on Rx-to-OTC switches, describes a hierarchy of consumer decisions in selecting an OTC drug: the “right for me” decision, the purchase, and finally the product use.

Additionally, FDA’s suggested self-selection question – “Is it okay for you to use this medication?” – could confuse a subject without additional context, says Brass, a professor at UCLA’s David Geffen School of Medicine, in a comment posted Nov. 14.

FDA’s position “that the purchase decision has ‘no bearing’ is an oversimplification,” he adds. “There should be flexibility based on the relevant clinical issues to use the endpoint suggested in the draft [guidance], or a purchase decision or a use decision (or more proximal surrogate).”

Other stakeholders voiced similar opinions on the purchase decision language; comments were due to FDA Nov. 18.

Contract research organization PEGUS Research, like Merck, supports the flexibility of using purchase decisions or other question formats to better understand how consumers think in an OTC setting.

“Asking about selection in more than one way helps subjects move from purely hypothetical reasoning to more meaningful, concrete responses based on their own personal health situations,” the Salt Lake City firm says in a Nov. 17 comment.

The Consumer Healthcare Products Association says purchase decision data provide insight into how consumers read drug product labels . The trade group also hopes FDA illustrates the “general and vague” guidance with real-world examples.