Clinical Endpoints Could Help Chronic Condition Drugs Switch

Companies attempting to switch a drug OTC for a chronic condition might have a stronger case if supported by data focusing on clinical endpoints rather than just markers, a workshop group surmised at the Consumer Healthcare Products Association Research & Scientific Development Conference in Washington, D.C. Oct. 28-29.

The topic arose during a brainstorming session in which various industry representatives discussed, from a regulatory point-of-view, what would convince them to allow an antihypertensive agent to be sold over-the-counter.

The group was one of four in the workshop, meant to consider the benefits of providing such a drug in both the Rx and OTC domains. The other groups assumed the positions of industry, healthcare practitioners and consumers.

The theoretical drug, a diuretic called "TensioStat-BP," came with an OTC label carrying the indication: "To treat elevated blood pressure that has been diagnosed previously by a physician. For use only in individuals with blood pressure readings in the range of 130-139/85-89 mm Hg."

Discussing what would most likely convince FDA the drug is appropriate for OTC use, the mock government group said data measuring a reduction in clinical endpoints such as stroke, myocardial infarction or progression of hypertension would be powerful.

Such data would show the drug's long-term effectiveness in the retail marketplace as well as consumers' ability to comply with its instructions for use over an extended period of time - both critical issues when deciding whether a drug for a chronic condition should be allowed for OTC sale.

The nine-member group believed these endpoints might provide a stronger argument for OTC use than studies simply measuring how much blood pressure decreased in people taking the medication in an OTC setting. An FDAer in another working group noted the agency does consider hypertension to be linked to an increased risk of MI and stroke.

Other data the government group speculated would be helpful to regulators consisted of evidence showing the quality of care available to patients with hypertension had "maxed out." If the treatment of hypertension with Rx drugs could not be improved upon and a drug had a good safety profile, then placing it the OTC arena would make sense as another treatment option, the group members hypothesized.

However, the group recognized that measuring the quality of care in the Rx setting is extremely difficult, and comparing these findings to OTC actual use study data only raises more questions. A SmithKline Beecham rep noted the firm accumulated roughly 10 years of data showing people's reluctance to visit their doctor for help in quitting smoking before finally receiving OTC approval for the smoking cessation products Nicoderm CQ and Nicorette.

The workshop participants also noted a clinical endpoint study poses serious problems, both in terms of funding and the length of time it would take to collect meaningful results.

These difficulties show the numerous challenges facing future switches; Rx-to-OTC medications have become increasingly uncommon as the drug categories attempting to switch have become more complex, tending to deal with chronic conditions such as hypertension and hypercholesterolemia.

Although it did not appear to be a central issue, the question of how OTC availability would compare to the standard of care in the Rx environment did arise during FDA advisory committee reviews of Bristol-Myers Squibb's hypercholesterolemia drug Questran.

In Bristol's second attempt to switch the drug in 1997, committee member Jose Francisco Cara, MD, noted without "any information that tells me that [OTC] treatment actually increases compliance [or] efficacy," he would vote against switching any cholesterol-reducing drug (¹ (Also see "Questran second advisory committee divided on OTC switch recommendation." - Pink Sheet, 19 May, 1997.)).

However, the CHPA workshop participants weighed the possibility that an OTC antihypertensive would contribute to an overall public health benefit. They agreed consumer advertising could raise awareness of the problem of high blood pressure, which could then lead to more people seeking treatment, better compliance and improved health outcomes.

Options such as package inserts, video/audio guides, 800 numbers and co-branding a blood pressure cuff with another firm were seen as possible ways to raise awareness of hypertension and boost OTC compliance.

In 1995, when BMS first attempted to switch Questran, it cited the public health benefit that would arise, noting in the Rx setting patients typically receive only 5-7 minutes with their doctor.