Most large, multiyear comparative studies are funded by NIH and frequently yield results that dismay manufacturers. Probably
the most controversial comparative study in the works is the National Eye Institute's assessment of treatment for age-related
macular degeneration (AMD). The aim of the study is to determine any difference in safety or effectiveness for patients receiving
Lucentis (ranibizumab), which is approved to treat AMD, or Avastin (bevacizumab), a colon-cancer therapy that has been widely
used off-label for AMD. Both drugs are produced by Genentech (South San Francisco, CA) and derived from the same monoclonal
antibody, but using Avastin to treat AMD costs less than one-tenth the price of Lucentis.
Comparative drug trials raise a host of logistical and regulatory issues for obtaining high-quality, uniform, and appropriate
comparator drug products. Sponsors often run into difficulties with comparator availability, cost, expiration dates, storage
requirements, and registration status. All these issues are compounded for global multisite studies that may require comparators
from different sources. And for blinded studies of solid oral dosage forms, comparators often must be reformulated and retested
to ensure uniform stability, dissolution, and bioequivalence. Study sponsors must document that comparators meet good manufacturing
practice guidelines, have appropriate expiration dates, and are registered for use in all study sites.
While the most reliable source for a high-quality comparator usually is the original manufacturer, sponsors often must look
elsewhere because of cost, strategic, and competitive reasons. Many manufacturers agree to supply comparator products for
research at a price, knowing that they will want similar access in the future. Several wholesalers and specialized comparator
suppliers facilitate such arrangements and ensure access to appropriate comparators to meet study needs.
Demand for comparator products may increase along with growing interest in independent drug–drug studies. Although pharmaceutical
companies want CE research to weigh medicines against surgery or other treatments, pharmaceuticals are ready targets because
much more information about drugs is available from clinical trials, outcomes studies, and adverse-event reports. NIH's lengthy
list of possible ARRA-funded research projects includes dozens of CE drug-research topics such as comparisons of new treatments
for fibromyalgia, depression in children, and for autoimmune rheumatic and skin diseases.
But focusing on drugs and devices "misses the point," says Wilensky. "The real explosion in costs is in medical procedures."
A Duke University study published in the New England Journal of Medicine in February 2009, for example, found that in certain situations, clot-busting drugs alone provided as much benefit for many
heart-attack patients as did drug-coated stents—at much less cost. The Pharmaceutical Research and Manufacturers of America
asked the IOM priorities committee to support studies that compare care processes, disease-management services, and benefit
design. In a white paper on CE research, the Biotechnology Industry Organization backs CE research on preventive services,
diagnostic tests, and medical procedures, as well as the interactions among components of the healthcare system.
A related industry concern is that a greater emphasis on broad patient responses to drugs and medical treatments will stymie
advances in personalized medicine and development of targeted therapies. CE research basically seeks to identify therapies
and to establish practice guidelines and treatment standards that are most beneficial for the largest numbers of people. Personalized
medicine, conversely, involves selecting treatment choices for small patient populations and making patient-centered choices
that may not conform to common practice guidelines. And therapies targeting rare or life-threatening diseases may not fit
CE study designs because of the small size and heterogeneity of these populations.
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. The group recently signed up former
Congressman Tony Coelho of California to headline its campaign to ensure that CE studies are well-designed, promote continued
medical innovation, and protect patient access to "advanced treatment options."
The challenge for policymakers and scientists is to develop research methods and systems that support informed standards of
care, along with the flexibility to address special needs. CE research advocates believe that the nation's bloated healthcare
system contains so much excess spending that even modest curbs on unnecessary use of costly products and services will be
beneficial. The CBO white paper notes that though some expensive new technologies and medical services provide enormous clinical
benefits, "some medical services could be used more selectively without a substantial loss in clinical value." Policymakers
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 and lower costs for everyone.
Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634, firstname.lastname@example.org