FDA will look at which should come first – benefits or risks – when it studies patients' response to three one-page prototypes of patient medication information.

Two versions of each prototype – one in which the Uses section occurs first, and the other with a Warnings box first – will be assessed in a study FDA says is designed to test the materials for "utility to the patient and comprehension of material in the broadest audience possible."

A Dec. 14 Federal Register notice seeking comments on the implications of the PMI study does not say how FDA will determine which information should be placed first. The agency does note that research indicates that clear signaling of the most important information can help readers prioritize the importance of that information and increase the probability that it will be subject to more complete mental processing.

The study will ask about a fictitious drug, Rheutopia (arixalate), for the treatment of rheumatoid arthritis, ankylosing spondylitis and plaque psoriasis.

Irrespective of placement, FDA already has made the benefits more apparent by expanding the Uses, or "What Does Rheutopia Treat?" section to describe improvements that are possible with the drug. Participants at a September 2009 meeting complained that without specifics on benefits, consumers cannot make a tradeoff as to whether the risks of a drug are worth taking (Also see "Single Patient Drug Leaflet Logical, Complicated To Achieve - Woodcock" - Pink Sheet, 5 October, 2009.).

For the Rheutopia prototypes, the Uses section, for example, points out the drug "reduces painful and swollen joints, slows joint damage, and improves mobility and the ability to do physical activities," as well as treats rheumatoid arthritis in adults.

MedGuide Added To Study

FDA is looking to the one-page PMI document to be a simpler alternative to the multiple pieces of paper that patients may now receive – potentially a consumer medication information packet, a patient package insert and a Medication Guide.

The final study plan includes an assessment of patients' response to a MedGuide as a control condition for the three one-page prototypes.

FDA decided to assess patients' view of a MedGuide after receiving comments on its original study plan that pointed out: "comparing variations of a short, one-page document limits the findings because there will be no comparison to a longer document, which may perform better."

Current plans call for a subset of study participants to be randomly assigned to read and answer questions about the MedGuide format.

The one-page prototypes are: a Drug Facts format following the conventions of over-the-counter labeling, a "minimal column" format in which information is presented in two columns, and a Column Plus format that duplicates the minimal column prototype but adds contextual information to the section on what information patients should tell their doctors.

Those documents are subject to different laws and regulations, complicating the conversion to a single piece of paper. Trying to eliminate the MedGuide is further complicated by its entanglement in the Risk Evaluation and Mitigation Strategy process. Both industry and Office of New Drugs Director John Jenkins favor separating MedGuides from REMS, at least to some extent (Also see "PhRMA Wants MedGuides Developed The Pre-FDAAA Way, Not Through REMS" - Pink Sheet, 26 July, 2010.).

Regulations To Follow

To make the transition to a simpler PMI system, FDA plans to draft new regulations that "may require revoking/replacing existing regulations, e.g., Medication Guides and PPIs (patient package inserts)," Olivia Lau, special assistant in the Office of Planning and Informatics, told "The Pink Sheet."

There is no timeline for instituting the new PMI approach, Lau said, noting that external stakeholders have expressed a preference for "a staged, phased approach for implementing the new single document solution for PMI."

Pilot programs to determine the best way to develop content, evaluation/testing and distribution standards may serve double duty in this area. "Efforts achieved in the pilots may be useful as incremental, interim solutions until the new regulation is final," Lau said.

Pharmacy and patient groups want FDA to review and approve PMI documents before they are distributed, but at a meeting this fall, agency officials indicated they do not have the resources to look at all such materials (Also see "FDA Must Maintain Oversight Role In PMI Development, Groups Urge" - Pink Sheet, 27 September, 2010.).

FDA Favors Public/Private Collaboration

For the agency the best path forward is through public-private partnerships involving all stakeholders.

"Once a system is in place that assures high quality PMI, development and consumer testing of PMI by drug manufacturers will be the most efficient way to fulfill the needs of patients," Lau pointed out.

"Such an approach will provide manufacturers and pharmacies with a quality framework for developing, testing, distributing and updating PMI, and will facilitate continual improvement of the information."

FDA hopes to have OMB sign-off on the study by June, at which point data collection will begin, and take four to five months to complete. RTI International, which assisted FDA in designing the study, will recruit participants, collect the data and assist in the analysis.

The study is designed to help with defining PMI content and format standards, but FDA is leaving open the possibility that consumers may not favor one particular format, order or set of information. In that case, PMI developers may have options, rather than one set of standards, Lau said.

The agency feels Rheutopia is a very close amalgam of an existing class of drugs because it has a complicated set of risks, is given by injection and has multiple indications. FDA elected to write the prototypes for a complex drug on the theory that if it could simplify patient medication information for such a medication, it could do so for drugs with simpler profiles.

However, FDA says, it may conduct future studies to assess the applicability of the results to other drug classes.

A Multi-Phase, Online Study

The study is designed to assess whether information in the prototypes is optimal. The first phase will consist of qualitative interviews in which participants say what they want and need to know. The second phase will involve quantitative assessment of participants' comprehension of important information in the documents.

Data will be collected via computer at training and testing facilities, with orientation and debriefing conducted by interviewers. Questions will be both open- and closed-ended.

The study will have two independent variables in a 3 x 2 design: the format (the three prototypes) and the order (the placement of either the warning or the indication first).

Participants will include adults diagnosed with one of the three conditions treated by the fictitious drug.

To ensure the study produces results applicable to all patients, participants will be prescreened to determine their health literacy and selected to obtain a reasonable representation of the general population; at least 30% will fall in the lower end of the scale.

The information will be presented at a fifth grade reading level and participants will be assessed for literacy level using a validated instrument to ensure there is a low literate cohort involved.

An additional study will be conduced on the Internet with 200 individuals with the same characteristics as the larger sample to complete the same questionnaire. This will evaluate whether presenting the prototype electronically alters patients' processing of the information.

By Cathy Dombrowski

FDA's Chicken Or Egg Question For Pharmacy Leaflets: Should Benefit Or Risk Come First?

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