Comparative Effectiveness Research: Challenges for Pharma

Switching Rx drugs to OTC and adding comparative data could broaden access to treatment, writes Jill Wechsler.

Great enthusiasm for personalized and patient-centered medicine is driving a host of innovative regulatory and research proposals. The Food and Drug Administration is seeking to promote informed self-treatment by switching some current Rx drugs to OTC status with additional “conditions for safe use.” Government support for Comparative Effectiveness Research (CER) offers new opportunities for researchers, payers, and pharma companies to identify optimal treatments for a broad range of medical conditions. The clamor for more information on drug use and effects in such “real world” situations is shaping clinical research and coverage decisions.

Promoting OTCs

As part of this overall effort to encourage Rx to OTC switches — thus increasing patient access to treatments for chronic conditions such as high blood pressure and cholesterol — the plan aims for strategies that can help consumers select and use medicines appropriately without going to a doctor. Under this “new paradigm” to improve public health, as described by agency officials at a two-day public hearing in March, manufacturers would ensure “safe use” of a newly turned- OTC medicine by utilizing information technology to enhance and document appropriate treatment. Information kiosks in pharmacies could direct consumers through self-diagnosis programs that check for risk factors contraindicating treatment and monitor testing to ensure appropriate care; pharmacists could supply personal counseling and additional oversight.

The expectation is that reducing the cost and inconvenience of visiting a doctor to obtain a prescription will encourage broader self-treatment — and promote adherence to recommended therapy after treatment begins. There’s strong evidence that such Rx-to-OTC switches for common conditions, including vaginal infections, allergies, and heartburn, have promoted effective care. At a minimum, “rescue medicines,” such as asthma inhalers would be candidates for enhanced pharmacy access.

Pharmacists are enthusiastic that this more flexible regulatory approach would expand their role in improving public health — and generate added fees for counseling and services. Vocal opposition comes from the American Medical Association (AMA), which insists that physician involvement in patient treatment is vital, especially for chronic diseases. Health plans and payers stand to save money because most insurers and health plans do not cover nonprescription medicines. This translates into higher out-of-pocket costs for individuals who have drug benefits, a shift that the AMA predicts will undermine adherence.

Pharma companies could benefit from increased sales of nonprescription products, but are fairly quiet about such prospects, particularly about how OTC switches often aim to retain market share for a brand facing generic competition. And drug distributors are uneasy about special programs that require wholesalers to determine which pharmacies and customers may receive a particular nonprescription product.

A policy that permits FDA to approve OTC products with added safe-use requirements would require a lengthy FDA rulemaking process and most likely authorizing legislation. It also would involve further development of label comprehension studies and actual use trials able to document that the medicine can be used safely and appropriately based on the approved “drugs facts box” label, plus supporting information and services. IT and research firms are ready with a range of strategies to support these efforts, including new ways to evaluate and ensure compliance with self-diagnostic tools, to devise collaborative programs that enhance care management, and to coordinate follow-up and oversight in collaboration with physicians, payers and patients. Despite regulatory, scientific, and political challenges, FDA leaders appear optimistic that innovative studies and IT systems not only can enhance medication use, but also identify drug interactions and improve pharmacovigilance tracking.

CER challenges

Another way to help patients and providers make informed decisions — and to save money by curbing inappropriate care — is by evaluating effective treatment strategies and comparative study methods. The Patient Centered Outcomes Research Institute (PCORI) is poised to distribute some $120 million in the coming months — and nearly $400 million in 2013 — to launch a federal CER initiative, as authorized by the Affordable Care Act. Pharma companies already are providing more comparative and outcomes analysis to formulary committees, insurers, and payers to bolster claims of product value, and the new program should further document real-world effectiveness for certain medical treatments.

PCORI has spent the last year getting organized, hammering out definitions for PCOR and CER, and seeking advice from all corners of the healthcare and research community. Last month it finalized priorities for its research agenda with an eye to awarding initial grants this fall. About $35 million will support studies to identify medical products and practices likely to improve patient outcomes for prevention, diagnosis, and treatment. Additional funds will support efforts to improve healthcare systems and to set standards for CER research methods, including less traditional approaches involving patient registries and meta-analyses.

The growing demand for real-world CER data has generated considerable discussion about the design of studies to demonstrate comparability and added value of pharmaceuticals. At a PCORI stakeholder “dialogue” in February, employers said it’s important to assess common chronic conditions that account for much of healthcare spending, while patient advocates urged analysis of treatment effects on individuals with less common critical diseases to avoid one-sizefits- all coverage decisions that often reject new technology.

These developments are prompting sponsors to address CER earlier in the drug development process, to engage stakeholders in clinical trial design activities, and to explore innovative approaches for generating evidence, said Eleanor Perfetto, senior director for reimbursement and regulatory affairs at Pfizer, at an April CER summit sponsored by ExLPharma. Similarly, experts at another CER conference organized by the Drug Information Association (DIA) and the National Pharmaceutical Council (NPC) in March discussed the need to assess co-morbidities, patient biology, and other characteristics likely to affect response. Peter Neumann, professor of medicine at Tufts Medical Center, advised sponsors to carefully choose comparators, outcomes, and subgroups to study.

A serious concern, though, is that too large and costly CER studies will stymie innovation. Clinical trials with multiple subgroups, active comparators, and long-term endpoints can make drug development more expensive, pointed out NPC research director Jennifer Graff at the ExLPharma conference. Such investment could pay off by supporting broader indications and higher prices for medicines found effective with certain patients, along with a higher probability of success for a clinical trial, faster FDA approval of a new product, and providing a basis for additional indications in the future.

Yet, Naomi Aronson, executive director of the BlueCross BlueShield Technology Evaluation Center, voiced skepticism that CER will greatly improve the evidence base for health plan decision making. And even if a pharma company can document that some patients do better on a new drug, if that therapy is too expensive, she said, the health care system still won’t be able to afford it.

To reduce costs and risks, pharma companies are forming partnerships with health plans and pharmacy benefit managers to assess treatment effects. A Pfizer-Medco partnership, Perfetto noted, aims to utilize genomic and phenotypic data in studies that match patients to treatments most likely to provide benefit. Similar collaborations are evaluating a range of real-world treatment strategies on patient subgroups and specific diseases.

These and other research initiatives highlight PCORI’s important role in setting standards for CER analysis and in coordinating CER activities to avoid redundancies. Dissemination of CER results also is critical to ensure that clinicians incorporate research findings into practice. PCORI will support communications activities by the Agency for Healthcare Research and Quality (AHRQ), which is holding a symposium in June to further discuss how research methods can shape the results of randomized trials and observational studies.

A hot issue for marketers is that FDA regulations constrain them from commenting on CER findings that invariably touch on unapproved uses of a medical product, even though the government, academics, payers, and insurers are free to disseminate and discuss all aspects of outcomes and comparative studies. At an NPC conference in February, Robert Temple, deputy director for clinical science of FDA’s Center for Drug Evaluation and Research, emphasized that industry is free to rebut clinical findings that they find objectionable, so long as they present factual and objective information — and avoid promoting off-label uses. Pharma companies want a more level playing field as CER plays an increasingly important role in shaping coverage decisions, but insurers and payers are leery that industry will use CER for promotional purposes. CER studies will be under ever-sharper scrutiny to ensure they avoid bias and encourage better care.