Biopharmaceutical companies also have been underwriting more comparative studies to meet regulatory and reimbursement requirements.
Payers and formulary committees weighing drug coverage options want data on superior efficacy and safety compared to available
treatments. More postapproval safety studies are comparing new drugs to existing therapies. Premarket clinical trials in Europe
and other nations routinely compare investigative products to comparators. Even the FDA, which generally prefers placebo-controlled
studies, finds comparative clinical information useful in documenting the advantages for new drugs in crowded therapeutic
classes or when serious safety issues emerge.
Johnson & Johnson's Centocor, for example, sponsored a large Phase 3 comparator trial to demonstrate that its new biologic,
ustekinumab, is more effective than Amgen's TNF inhibitor Enbrel (etanercept) for treating patients with psoriasis. Eli Lilly
has compared its anticlotting drug, prasugrel, to field leader Plavix (clopidogrel) to better assess efficacy and reports
of internal bleeding. GlaxoSmithKline is testing its new type 2 diabetes treatment, Syncria (albiglutide), against multiple
active comparators, such as metformin, insulin, and others. The multi-arm, 4,000-patient study aims to show clear benefits
over existing treatments for a therapy that may require less frequent dosing.
Such large comparative studies are usually funded by the NIH, which has the resources to carry out long, multisite assessments.
These can be controversial, as with the National Eye Institute's assessment of treatments for age-related macular degeneration.
The aim is to determine any difference in safety or effectiveness for two similar Genentech therapies, Lucentis (ranibizumab)
or Avastin (bevacizumab).
Comparator drug trials require manufacturers to address a host of logistical and quality issues to obtain appropriate comparative
products. Sponsors routinely run into difficulties dealing with product availability, expiration dates, storage requirements,
registration status, and costs. Comparators often have to be reformulated and retested for studies that require patient blinding.
And all these issues are compounded for global multisite studies using comparators from different sources.
Manufacturers would like federal CE research initiatives to focus less on drug–drug comparisons and more on the effectiveness
of various care processes. A white paper on CE research from the Biotechnology Industry Organization (BIO) urges more analysis
of preventative services, diagnostic tests, and medical procedures, and how components of the healthcare system interact.
Focusing on drugs and devices "misses the point," says health policy expert Gail Wilensky. "The real explosion in costs is
in medical procedures."
The industry is also concerned that CE research could stymie the development of more targeted therapies that are integral
to advancing personalized medicine. Comparative studies basically aim to identify drugs and establish treatment standards
that are most beneficial for the largest numbers of people. Personalized medicine, conversely, involves treating small patient
populations in ways that often differ from practice guidelines. CE studies frequently are not appropriate for therapies that
target rare or life-threatening diseases affecting small patient subgroups. Drug and device makers have formed the Partnership
to Improve Patient Care and enlisted support from patient and medical groups to press for CE research on clinical value and
outcomes, as opposed to cost effectiveness.
Policy makers insist that CE research will not lead to coverage denials, but will steer doctors and providers to treatments
that offer greater benefits for particular patients. The important questions, Wilensky notes, are whether CE data has credibility,
whether research practices are open and transparent, and whether studies are objective and not politically motivated.
Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, firstname.lastname@example.org