Author: webguru2

Mobile Health Apps Could Support Novel Rx-to-OTC Switches Suggests New Research from PinneyAssociates

Americans concerned about blood pressure may be more likely to try an OTC blood pressure medicine that had a companion mobile health app, and over 50% of participants in an online survey indicated they would be willing to pay more for the OTC product when it had a companion mHealth app.

“Results of our survey suggest that consumers are eager for mobile apps that will help them manage common diseases, which can help to enable Rx-to-OTC switches of products by supporting appropriate self-selection and actual use,” commented Michael Hufford, PhD.

Dr. Hufford presented the results of this PinneyAssociates survey at the 2017 Consumer Healthcare Products Association (CHPA) Annual Executive Committee (AEC). Using Amazon’s Mechanical Turk, an online crowdsourcing marketplace, PinneyAssociates was able to quickly recruit hundreds of people who were concerned about their high blood pressure and have them complete a brief survey about their interest in, and willingness to pay for, an OTC blood pressure medication with or without a companion health app.

“For Rx-to-OTC switch, the easy switches are behind us,” commented Saul Shiffman, PhD, at the 2017 CHPA Regulatory, Scientific & Quality Conference (RSQ). “Apps are more suitable in the context of complex Rx-to-OTC switches, for managing ongoing use and for products that treat chronic asymptomatic conditions.”

If an app is to be used as part of a switch, testing of the app needs to encompass if the app works as intended relative to the Drug Facts Label (DFL), usability by the intended population, and demonstration of an evidence-based approach. Recently, the FDA has been encouraging sponsors to embrace digital health innovations. (see here and here) As Dr. Gottlieb recently noted in “Fostering Medical Innovation: A plan for Digital Health Devices (June 15, 2017), “To encourage innovation, FDA should carry out its mission to protect and promote the public health through policies that are clear enough for developers to apply them on their own, without having to seek out, on a case-by-case basis, FDA’s position on every individual technological change or iterative software development.”

PinneyAssociates’ presentations at CHPA AEC and RSQ can be found here and here, respectively.

To learn more about our Rx-to-OTC Switch Services, click here.

Rx-to-OTC Switch: Developing a Compelling Science-Based Submission for the FDA

An Rx-to-OTC switch submission depends on well-designed consumer studies that show consumers can follow the Drug Facts label and use a drug safely and effectively in the nonprescription setting.

Our experts can help you:

  • Draft and evaluate OTC Drug Facts Labels, Consumer Information Leaflets, and behavioral support materials
  • Plan and help design the overall development program, including label comprehension studies, self-selection studies, actual use trials and tailored consumer studies

Drs. Janine Pillitteri and Christine Sweeney are two of our behavioral scientists who can help make your Rx-to-OTC switch submission a reality.

Assessment of Abuse Potential in Clinical Trials: The Finalized FDA Guidance

What does the future hold for abuse potential now that FDA has finalized the Guidance on Assessment of Abuse Potential of Drugs? Jack Henningfield, PhD, chaired a workshop at the College on Problems of Drug Dependence (CPDD) to address this topic.

“The science of abuse potential has evolved enormously in recent decades. The FDA’s 2017 Guidance captures this as applied to medicines and other substances. It provides the basis for an orderly and more predictable process for drug development and regulatory decision making.” said Dr. Henningfield. “We urge sponsors to reference the FDA guidance when planning and designing studies and to discuss alternative approaches with the Agency. Phase 3 studies, in particular, often require working within practical constraints and reliance on indirect measures such as spontaneous AE reports that might, but do not necessarily, reflect abuse, dependence or withdrawal.”

Workshop topics included:

  • The process of documenting abuse-related signals from clinical trials, Silvia Calderon, Pharmacologist, Controlled Substances Staff, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
  • Development of a standardized classification system for assessing abuse potential in clinical trials: ACTTION recommended considerations, Shannon Smith, Assistant Professor of Anesthesiology, University of Rochester School of Medicine and Dentistry
  • Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®), Nathaniel Katz, CEO, Analgesic Solutions
  • Assessing abuse potential from soup to nuts: Nonclinical and clinical study data that inform label claims and CSA scheduling recommendations, Katherine Bonson, Pharmacologist, Controlled Substances Staff, Center for Drug Evaluation and Research, U.S. Food and Drug Administration

Dr. Henningfield’s presentation can be found here.

To learn more about our abuse potential assessment services, click here.

FDA Workshop on Abuse Deterrent Opioids: Distinguishing Products in Postmarketing Surveillance to Support Category 4 Labeling

Understanding the real-world effectiveness and value of abuse-deterrent opioids depends on surveillance designed to evaluate how these formulations work in the real world, product by product, and distinguishing prescription opioids from illicitly produced street products, such as counterfeit synthetics.

Drs. Sid Schnoll and Jack Henningfield both reinforced this message in a public workshop organized by the FDA in July on “Data and Methods for Evaluating the Impact of Opioid Formulations with Properties Designed to Deter Abuse in the Postmarket Setting: A Scientific Discussion of Present and Future Capabilities”. Dr. Schnoll participated as an invited member of the workshop panel, and Dr. Henningfield presented during the public comment period.

Prescribing and market share of abuse deterrent opioids is very small compared to non-abuse deterrent opioids, largely because of pricing. That makes tracking their impact particularly challenging for surveillance. Abuse-deterrent formulation of opioids constitute one piece of the puzzle to addressing the overall public health goals of preventing and reducing opioid abuse, addiction, and overdose in America. Their effectiveness and value to comprehensive opioid control efforts must be evaluated by measures that are appropriate to what these formulations are designed to do.

“Going forward we need to be careful to distinguish surveillance designed to evaluate how well AD opioids are working to achieve the goals that they are designed to do, product by product, such as reduction of insufflation and injection, rather than stopping the overall abuse of opioids,” said Dr. Schnoll.

Part of the challenge for surveillance is actually relating specific products and substances with abuse and overdose. Most overdose deaths involve the ingestion of several substances yet the headlines often refer to whatever drug happens to be in the media spotlight at the time or confuse illicitly made and distributed synthetics such as fentanyl and analogs with prescription drugs. Similarly, most prescription drug abuse and overdose occurs in people who did not have prescriptions yet are discussed as though they were prescribed pain patients – a population that overall shows very low rates of abuse and overdose.

FDA has yet to describe the requirements for Category 4 labeling, meaning that sponsors have the opportunity to propose study designs. PA experts design and execute postmarketing surveillance for a range of controlled substances, including abuse-deterrent formulations of opioids. Our experts can design prospective or retrospective cohort studies and integrate epidemiology and other data with the cohort study results.

Opana ER: What other questions could have been asked?

PA experts observing the recent marketing withdrawal of Opana ER (oxymorphone hydrochloride) considered other data that could be examined to determine if there is something inherent to the formulation that encourages more dangerous avenues of abuse, and the impact of other external factors on real-world safety.

On July 6, Endo Pharmaceuticals announced it would withdraw Opana ER from the market. This followed a March meeting of FDA’s Drug Safety Risk Management and Anesthetic and Analgesic Drug Products Advisory Committees in which committee members voted 18 to eight that the benefits of the formulation no longer outweigh the risks. Opana ER has been implicated in outbreaks of a Thrombotic Thrombocytopenic Purpura (TTP)-like illness in northeastern Tennessee and an HIV outbreak in southern Indiana. While Opana ER was not approved for labeling as abuse deterrent, Endo’s marketing of the product referenced the product’s formulation with Grunenthal’s INTAC® Technology which was intended to create a crush resistant product.

In the case of Opana ER, we note that other external factors potentially impacting the severity of the TTP and HIV outbreaks may have included how the drug was prepared for injection, other drugs injected with it, a shortage of syringes, criminal penalties (Indiana only) for possession of syringes, and lack of access to methadone/buprenorphine treatment.

Based on the publicly available information on Opana ER, companies may want to consider the following:

  • Completing all abuse potential studies requested by the FDA
  • Conducting heat pretreatment studies, with appropriate comparators
  • Collecting and analyzing geographic-specific post-marketing surveillance data, including the collection of baseline data
  • Conducting thorough surveillance, including field research, in the localities affected, to determine external factors potentially impacting these public health issues

PA scientists and experts prepare preliminary abuse potential assessments to determine gaps in the abuse potential assessment program, develop protocols for laboratory assessment of the abuse characteristics of product formulations, and develop and execute postmarketing surveillance, including field research.

Note: PA did not provide support to Endo on Opana ER development, abuse potential assessment, or regulatory strategy.