Intangible Benefits Are Influential In OTC Switch Decisions – CDER’s Ganley

Non-measurable benefits can tip the scales in the benefit/risk consideration of an OTC switch NDA, suggests Charles Ganley, director of CDER's Office of Drug Evaluation IV. One way to look at non-measurable benefits is how OTC ingredients "lower the threshold” for patient “misery” prior to seeking relief, he says.

OTC switch application sponsors should identify “non-measurable” aspects in a candidate ingredient’s benefit/risk profile, says FDA Center for Drug Evaluation and Research official Charles Ganley.

“We know how to measure benefit for a lot of diseases, but what is difficult in many cases is the non-measurable benefit of a drug going OTC,” he said May 20 in a presentation on benefit/risk assessments at the Consumer Healthcare Product Association’s 2016 Regulatory, Scientific, & Quality Conference in Rockville, Md.

“We don’t generally think about this, when we think about benefits, but we’d suffer a lot more if these drugs weren’t available,” said Ganley, director of CDER's Office of Drug Evaluation IV, which includes in the Division of Nonprescription Products.

Discussing multiple ways to think about defining benefits from a candidate in an Rx-to-OTC switch new drug application, Ganley explained that non-measurable benefits consider the impact of a drug’s absence from the market and, in many cases, related increases in doctor appointments.

One way to look at intangible benefits from ingredients being available nonprescription is “they lower the threshold” for patient “misery” prior to seeking relief, he said.

“Envision there are no pain relievers available over the counter” and “if you have a headache … you’d probably allow yourself to suffer and be in misery for a while before going to the doctor,” he said. “But because pain relievers are available OTC, patients may be inclined to take them before they reach the threshold that would cause them to see a doctor."

“We don’t generally think about this, when we think about benefits, but we’d suffer a lot more if these drugs weren’t available.” – Charles Ganley, director of CDER's Office of Drug Evaluation IV

Non-measurable benefits also could be applied to a benefit/risk assessment for antihistamines as well as many other types of OTC products as part of a sponsor’s overall methods to measure social and behavioral science as part of their switch NDAs.

CHPA frequently notes research it commissioned showed that every $1 spent on OTC drugs saves the US health care system $6 to $7. The trade group and other consumer advocates make the point in lobbying to amend the Patient Protection and Affordable Care Act to again allow direct purchases of OTC drugs using health savings accounts (Also see "CHPA Quantifies OTCs’ Overall Value To Promote Expanded Access" - Pink Sheet, 6 Feb, 2012.).

A Factor In FDA Reviews

Ganley stopped short of recommending tools to demonstrate non-measurable benefits while saying he considers intangible benefits when he reviews an application. “I generally try to factor those things in, understanding that that’s something that we really underappreciate,” he said.

In 2013, FDA released a new approach on benefit/risk assessments under its Prescription Drug User Fee Act V Implementation Plan for fiscal 2013-2017. In the plan, to facilitate and balance the benefits and risks of OTC switches, FDA delineates a “qualitative descriptive approach,” that involves filling in a benefit/risk framework grid with quantitative evidence, leading to a series of conclusions and a summary assessment (Also see "CDER Benefit/Risk Assessment Tool Has Room For OTC Considerations" - Pink Sheet, 28 May, 2012.).

Some companies have used that approach effectively. In 2013, Merck & Co. Inc. achieved a first-in-class OTC switch for Oxytrol for Women (oxybutynin), a transdermal patch for overactive bladder. The firm demonstrated the benefit of the product partly by showing that 80% of women were not seeking care for overactive bladder (Also see "CDER Benefit/Risk Assessment Tool Has Room For OTC Considerations" - Pink Sheet, 28 May, 2012.).

Also during the benefit/risk session, Eric Brass, a former chairman of FDA’s Nonprescription Drugs Advisory Committee and a professor of medicine at the David Geffen School of Medicine at the University of California-Los Angeles, agreed with Ganley that sponsors should consider more ways to measure the benefits of drugs that lower the threshold for patient suffering.

“I think there is potential to begin measuring things like that, and to develop tools to better understand how consumers view the impact of symptoms and then translate that concept into more measurable [patient-reported outcome] type of assessments that would give real insight into what the real clinical benefit is,” Brass said.

“To be able to have that access, lower that threshold, to access effective medication, really does have an impact for consumers that is well recognized.”

Opinions Differ About Science

Ganley spoke to the frustration sponsors have expressed regarding inconsistency between opinions by FDA officials and advisory committee members on OTC switch applications.

“Scientific judgments can lead to different individual opinions and conclusions for risk assessment,” he said.

“So there may be two experts who agree on a set of facts regarding benefits and risks. But experts could not agree. I know this is industry’s greatest concern.”

Ganley pointed out the agency's decisions on drug applications are limited by regulatory constraints. “Sometimes we agree with you and sometimes we can’t. Sometimes we can’t agree on science, and science can dictate policy. This can be as frustrating for us as it is for you.”

On its website, FDA notes that no risk/benefit assessment is “easy” and the agency decides each OTC switch on a “case-by-case basis.”

Still, Ganley said switch NDA sponsors should broaden their approach to consumer study data and their benchmarks for study success, which are “not always defined by reaching some threshold of correct self-selection and use. Understanding how decisions are made or not made are of equal importance.”

As an example, he noted FDA’s 2003 approval of AstraZeneca PLC's Prilosec OTC (omeprazole), marketed by Procter & Gamble Co.as the first proton pump inhibitor switched OTC (Also see "P&G Asks FDA To Make Prilosec The Standard For OTC PPI Claims" - Pink Sheet, 27 Apr, 2009.).

“Their last actual use study didn’t meet some thresholds, but they had done a very good job with information showing consumers were using the products correctly,” Ganley said.

He briefly discussed possibilities for the Non-Prescription Safe Use Regulatory Expansion initiative for facilitating novel technologies to promote OTC switches.

“The NSURE program is something that I hope comes to fruition while I’m still at FDA, because I believe if it’s done correctly, it could revolutionize what products you see on the market in ten, fifteen, twenty years,” he said.

The previous day at the conference, in response to frustration expressed over a lull in activity for NSURE, Dominic Cirincione, FDA’s regulatory counsel in CDER’s Office of Medical Policy, said the center is “working towards finalizing the framework” for implementing changes in the drug application process that will help sponsors propose novel switches (Also see "CDER Talks Switches, Monograph 'More Than Ever,' But Mum On Changes" - Pink Sheet, 23 May, 2016.).