BETHESDA, Md. _ In a move both feared and expected by drugmanufacturers, the Division of Drug Marketing, Advertising andCommunications (DDMAC) at the FDA's Center for DrugEvaluation and Research (CDER) has drafted a rigorous set of"principles" for the regulation of cost-effectiveness claims inpromotional materials.

Although the principles came showered with caveats _ theyrepresent "only the views of DDMAC and have not been reviewed byothers at the FDA" and do not represent "CDER or FDA policy orguidance" _ it's clear that the agency intends to regulate thedissemination of pharmacoeconomic data and to serve as an arbiter ofits credibility.

A DDMAC draft paper dated March 20, 1995 was circulated here atan FDA conference on the methodological morass surroundingcomparative and cost-effectiveness studies last Thursday and Friday.More than 500 representatives from the pharmaceutical,biotechnology, health care provider and insurance industries, as wellas government regulators, consultants and academics attended twodays of standing-room only sessions on the thorny topic.

"Among all the practitioners and evaluators of this relatively new andevolving discipline, only the FDA must come to grips immediatelywith what is permissible and what are the standards," CDER DirectorJanet Woodcock told conference attendees.

Though the prospect of the FDA extending its regulatory reachbeyond safety and efficacy into cost-effectiveness may rank as one of the drug industry's worstnightmares, some believe it is inevitable. The agency has statutoryauthority over labeling, advertising and promotion, the three majorarenas in which cost-effectiveness data will be used.

As Woodcock pointed out, the alternative to FDA regulation could bechaos. "Few firms will wish to see their product fail in themarketplace due to dubious claims of cost-effectiveness that havebeen intensively promoted by a competitor," she noted.

Skyrocketing health care costs in the U.S. have led once-decentralized and weak providers to coalesce into large, powerfulbuyers. Those buyers are demanding that drugs clear higher andhigher hurdles of efficacy and economy before they are allowed ontohospital formularies. Inclusion on a formulary, the list of drugsapproved for use at any given medical institution, is a matter of life ordeath for individual drugs and, in some cases, for the companies thatmake them.

Customers Demand Cost-Effectiveness Data

As a result, pharmaceutical executives can barely stop to congratulatethemselves on winning FDA approval before they must face an eventougher challenge _ that of winning over increasingly sophisticatedand skeptical pharmacy and technology (P&T) committees at thenation's largest health care product purchasing organizations. Simplyput, P&T committees want cost-effectiveness data and they want itnow.

"Customers want cost-effectiveness data prior to the launch of aproduct," lamented Raymond Townsend, vice president ofinternational applied health care research at U.K.-based GlaxoHoldings plc and a conference speaker. Yet the type of data neededfor FDA approval, a randomized, controlled clinical trial testingsafety and efficacy under strictly defined, or "ideal," circumstances isregarded by most P&T committees as useless. They want to knowhow a drug performs, both clinically and financially, "in the realworld."

Enter the fledgling and hotly debated "science" of designing,conducting and analyzing cost-effectiveness studies. Properlydesigned, such studies might demonstrate how a drug performs whenadministered to a broad range of patients, not those carefully selectedby entry criteria, and when administered by average physicians,rather than highly trained clinical investigators.

In addition, these studies could show how one drug performs betterthan its competitors or how it saves money. Thus by definition, cost-effectiveness studies are comparative. There's only one problem. Thefield of comparative research is a theoretical, statistical andmethodological minefield, according to the FDA.

Bias Potential Means HMOs Disregard Studies

One major problem is that these expensive studies are almost alwaysconducted by drug companies, leaving them vulnerable to charges ofbias in design and/or interpretation. Indeed, P&T committees at largehospitals or health maintenance organizations (HMOs) oftendisregard industry-sponsored research in favor of studying their ownpatient data bases.

Almost everyone in the health care industry agrees on the need forstrong scientific standards in the field of cost-effectiveness researchbut the burning question remains, who should set the standards?

Industry has argued that it could voluntarily adopt principlesdeveloped by experts, such as Alan Hillman at the University ofPennsylvania's Leonard Davis Institute of Health Economics.Hillman and his colleagues have formed a task force to develop justsuch a set of standards. The Pharmaceutical Research andManufacturers of America recently published (January 1995) a set ofmethodological and conduct principles for pharmacoeconomicresearch.

Theoretically, if industry agreed to a standard set of principles, theremight be no need for government regulation. Another idea offered byindustry: allow for unbridled dissemination of pharmacoeconomicdata to "highly trained" Pharmacy Benefit Managers (PBM) andP&T committees and let them decide for themselves how validindustry studies are.

However, as last week's conference and working document onprinciples make clear, the FDA _ at least for now _ feels it isuniquely qualified to judge the validity of cost-effectiveness research.The FDA's draft "Principles for the review of pharmacoeconomicpromotion" is an attempt to clarify the agency's present views on theevolving science of comparative and cost-effectiveness studies. Itoutlines general principles for pharmacoeconomic promotion, claimsubstantiation, analytical considerations, disclosure to preventmisleading or false claims, and "quality of life" (QOL) claims.

According to the document, the FDA believes thatpharmacoeconomic claims, including cost-effectiveness and QOLclaims, should be substantiated by "adequate and well-controlledstudies," including placebo, active and historical control studies. TheFDA plans to review substantiating data, just as it does for new drugapplications and product license applications, in order to evaluate thevalidity of the conclusions reached.

`Substantial Evidence' A Must In Drug Comparisons

When direct comparisons between medications are made, the FDAbelieves that "substantial evidence," usually demonstrated by "twoadequate and well-controlled studies," should be offered in support ofthe claims. In addition, studies used to support pharmacoeconomicclaims should be scientifically rigorous and devoid of major sourcesof bias.

Although the seven-page draft principles document appears to setsome daunting _ and costly _ standards for cost-effectivenessresearch, FDA officials said repeatedly that it is not a "regulatorypronouncement." Industry's view was perhaps best embodied byTownsend, who said, "Is it possible or practical to meet FDArequirements for `proof' to substantiate the pharmacoeconomicinformation that we are being asked to provide to our customers? Ihave no answer." n

-- Lisa Piercey Washington Editor

(c) 1997 American Health Consultants. All rights reserved.