FDA Targets Acetaminophen Safety Evaluation In Plan To Mine OTC Use Data

An RFP to provide FDA with direct access to data on consumers’ OTC use identifies the public health impact of potential changes in dosing information on acetaminophen product labels as one reason for the planned data evaluation. Access to the data also will increase FDA’s ability to perform regulatory impact studies, particularly to assess the impact of Rx-to-OTC switches.

FDA plans to evaluate data on consumer over-the-counter drug use, provided from surveys conducted by a contractor, to help the agency respond to potential “serious public health or regulatory issues related” to the products.

A July 10 request for proposals from contractors to provide FDA’s Office of Surveillance and Epidemiology with direct access to data on consumers’ OTC use identifies the public health impact of potential changes in dosing information on acetaminophen product labels as one reason for the planned data evaluation.

The information “will help determine whether the changes, once implemented, have been effective in decreasing the adverse outcomes related to acetaminophen overdose,” according to the RFP.

Additionally, the RFP explains that continued direct access to OTC drug utilization data will increase FDA’s ability to perform regulatory impact studies, particularly to assess the impact of Rx-to-OTC switches, and strengthen the utility of the agency’s current adverse event reporting system.

FDA’s Center for Drug Evaluation and Research began addressing concerns about the public health problem of liver injury linked to the use of acetaminophen in OTC and Rx products following a 2009 joint meeting of the Drug Safety and Risk Management, Nonprescription Drugs and Anesthetic and Life Support Drugs advisory committees meeting. The efforts include changes in the dosing along with increased education for prescribers and patients (Also see "Lower Acetaminophen Doses Recommended Despite Cost Impact, Lack Of Data" - Pink Sheet, 6 Jul, 2009.).

OTC Drugs And Demographics

FDA’s RFP identifies OTC drug-specific basic data elements including:

• brand name
• active ingredients
• unit price code and/or national drug code number
• strength of active ingredients
• dosage form
• size of drug product by mL
• number of tablets/capsules and/or total doses available
• manufacturer and/or re-packager
• date of purchase
• indication for use or ailment intended to treat
• source of drug, such as recommendation by health care professional, self-purchase or sample provided.

The contractor also will provide:

• data on the number of households and household panel members in the survey sample
• characterization of households in the sample in terms of individuals in the household, income level, geographic region and U.S. Census region, compared to national figures where possible
• household demographic data including the number and percent of patient populations of special interest to the FDA – children under 2 years, children 17 and younger, women of childbearing age, adults and people 65 and older
• number and percent of patients missing age as well as the demographic distribution of patients, with age and gender required and race, if available.

The patient-specific basic data elements in the household include:

• patient demographics of the intended user such as age
• gender, and specify if other data elements are available, such as race/ethnicity; income level
• occupation
• height and weight
• clinical measures, i.e., blood pressure, cholesterol, smoking status
• alcohol use
• availability of health insurance
• geographic region.

The contractor will provide treatment-specific basic data elements that describe:

• a consumer’s ailment treatment category
• concomitant use with other Rx or OTC drug products
• duration of use
• diagnosis code
• patient demographics of the intended user.

The joint advisory panel recommended FDA make a "top priority" of lowering the maximum adult single dose of acetaminophen to 650 mg from 1,000 mg– two 500-mg tablets – and lowering the daily maximum dose from 4 g.

FDA in January said it will address OTC acetaminophen product dosing in a regulatory action separate from its since-conducted withdrawal of approval for Rx drugs with more than 325 mg per dose. The agency did not say how it would implement a change in maximum allowed OTC acetaminophen dose (Also see "In Brief: FDA responds to Nasacort suit, acts on acetaminophen and continues medical food enforcement" - Pink Sheet, 20 Jan, 2014.).

The Consumer Healthcare Products Association disagreed with the advisory committees' recommendation, noting studies show acetaminophen is safe at the current maximum daily dose of 4 g and may be safe up to 6 g. CHPA argues most unintentional overdoses are not from consumers taking too much of an OTC acetaminophen-containing product, but from taking prescription combination products that they are unaware also include acetaminophen.

Determining National Patterns

According to the RFP, FDA will award a contract for up to $1.5 million for a service that provides continuous automated access to data, compiled from a survey of household purchasing patterns or other electronic sources, on OTC drug product usage including household demographics, drug treatment patterns and indications or ailments intended for treatment in an outpatient setting.

FDA expects to award a contract with one base year and two option years. The RFP states that any questions on the project are due by July 18 and proposals are due by Aug. 11.

The service will provide data for an acetaminophen evaluation plan developed by a working group within CDER’s acetaminophen steering committee.

The RFP states FDA requires access to the data to obtain national patterns of OTC drug product use. The data resource must be capable of providing both current and historical national-level OTC drug product use with a maximum of a six-month lag between the date of a product purchase and when corresponding data are available to FDA.

FDA asks the contractor to provide agency staff with direct access to a currently existing, commercially available data resource through an existing interface tool for OTC drug use.

The user interface tool of the data resource will allow FDA staff to select OTC market categories with the ability to drill down to active ingredient, generic and brand name, and any other data elements that may be available.

The interface tool will include the ability to perform data reports with or without minimal intervention by the contractor and download the data in a timely manner, according to the RFP.

The interface will “be user-friendly, transparent, and flexible enough to meet the FDA’s needs,” and at minimum will “provide both predefined (e.g., canned) and custom reports.”

Direct access to the data resource will ability to download, or obtain in a timely manner through other means, and analyze patient level data, if available. The agency’s preference is that unrestricted direct access to datasets will be available on demand and without intervention by the contractor.

The data also will have the capability of providing national patterns of OTC drug use patterns in the outpatient setting through projection or other appropriate methodologies scientifically sound and transparent to FDA personnel, according to the RFP.

The contractor must “de-identify” the data – removing consumer information such as name, address, social security number and date of birth – to prevent any user from purposefully or inadvertently discovering a patient’s identity. Methods to de-identify data are required in proposals and must be complaint with the Health Insurance Portability and Accountability Act.

The data resource also will include a coding system of drug and ailment coding levels for FDA data analyses; and if available, quantify the amount, frequency and duration of OTC drug products used as well as the ailment intended to treat in the outpatient setting and the percentage of missing or incomplete information for each data element.

FDA’s authority “to obtain and expand database resources that will enhance FDA’s post-market surveillance capabilities” comes from provisions of the FDA Safety and Innovation Act of 2012, also known as Prescription Drug User Fee Act V.

[Editor’s note: Each week, “The Pink Sheet” DAILY features a story from “The Tan Sheet,” highlighting a current topic in the consumer medicines or nutritional supplements sectors.]