WASHINGTON In an attempt to enroll morediverse patient populations in clinical trials andcollect better data on differences in the wayminorities and women respond to diseases anddrugs, the National Institutes of Health (NIH) haspublished broad new guidelines for NIH-fundedresearch.The guidelines, published on March 9 in theFederal Register, include several significantchanges to guidelines published in 1990. Theystate that the NIH must:ensure that women and members of minoritypopulations and their subpopulations areincluded in all human subject research;in Phase III clinical trials, ensure that womenand minorities and their subpopulations beincluded such that valid analyses of differencesin intervention effect can be accomplished;not allow cost as an acceptable reason forexcluding these groups;initiate programs and support for outreachefforts to recruit these groups for clinical studies.Although the guidelines apply only to projectsreceiving NIH financial backing, drug companiescould eventually feel the impact. The NIH, withan $11 billion annual budget, wields enormouspower over the standards and practices ofmedical research."We're moving the whole scientific community inthe direction of looking at whether gender andrace are relevant factors in clinical research,"said Carlos Caban, director of extramuralprograms in the NIH Management Office.Caban said that institutional review boards(IRBs), the committees at universities andhospitals that must approve the protocol of anyclinical trial before it can begin, may wish toadopt uniform standards for all trials. Thus, IRBsmay simplify procedures by extending the newNIH standards for patient diversity to non-NIHtrials as well.The new guidelines state that if early clinical dataindicate a drug has important gender- orrace/ethnicity-based differences in effect, clinicaltrials must be designed to quantify that effect interms of clinical or public health importance. Fordrugs that have no scientific evidence of gender-or race-based differences in effect, requirementsfor including women and minorities would bewaived.Other trials eligible for a waiver of therequirements would include cases in which theresearch was inappropriate with respect to thehealth of the subjects or the purpose of theresearch and special cases determined by thedirector of the NIH.The new guidelines will kick in when a Phase IIIclinical trial is proposed for NIH funding. At thattime, data must be submitted to show whethergender or race differences in the interventioneffect are to be expected. Such data couldinclude animal studies, clinical observations,metabolic, genetic and pharmacology studies,and observational, natural history andepidemiological studies.The new guidelines were effective on March 9,although the NIH will review comments andconsider modifications to the guidelines for oneyear.Experts said that some clinical trials may have toenroll more patients in order to reach thenumbers at which subpopulation differences arevalid. Increased numbers would inevitablytranslate into higher costs and longer timeframes, but some have argued, better science."Capturing male-female differences in responseand differences in minority group responsesallows for more robust study design," saidCaban. "It's going to have a positive impact."While the inclusion of minority subpopulationshas been praised as a worthy goal bypharmaceutical industry representatives, it hasalso been criticized for unfeasibility. Examples ofa subpopulation of a minority group would beCuban-Americans, Puerto Ricans and Mexican-Americans, all component parts of a largerethnic group defined as Hispanics.Lionel Edwards, chairman of the specialpopulations committee of the PharmaceuticalManufacturers Association, said that the FDAdoes not currently require recruitment of minoritysubpopulations. He said he did not believe that itwas feasible for drug companies to capturerelevant information on small minority groupssuch as North American Indians, who compriseless than 1 percent of the U.S. population."That would just be extraordinarily expensive,"Edwards told BioWorld. "These NIH guidelinesare a social document as much as scientificone." He said he worried that clinical trials couldbe "subgrouped to death" by too manyrequirements like the NIH guidelines. He addedthat industry has become much more sensitiveto studying data about gender and minoritydifferences in recent years due to FDAregulations already in place.The NIH guidelines were spurred in part bycriticism from activist groups, Congress andothers who have claimed that a majority of drugsare tested for safety and efficacy primarily inwhite males. Questions have arisen as towhether a drug approved based on data fromwhite males can be used by a more diversepatient population with any real assurance ofefficacy.The FDA, final arbiter of safety and efficacy forall clinical trials, published its own set ofguidelines for the evaluation of genderdifferences in clinical trials in the FederalRegister last July. According to Robert Temple,director of FDA's Office of Drug Evaluation I, noclear evidence exists to suggest that womenhave been systematically underrepresented inclinical trials.However, Temple said that differences betweenthe responses of men and women to drugs anddiseases have not been adequately studied. TheFDA guidelines address that deficiency, he said.Last month, the Washington, D.C.-basedInstitute of Medicine (IOM) published a report onethical and legal issues relating to the inclusionof women in clinical trials. Among other things,that report came to the controversial conclusionthat pregnant women and women of child-bearing age should not be routinely excludedfrom experimental drug trials as has been thecase since the late 1950's (the new NIHguidelines reiterated this point).Shiriki Kumanyika, professor of epidemiology atPennsylvania State College of Medicine and oneof the authors of the IOM report, said that clinicalinvestigators often recruit patients for trials onthe basis of convenience."Investigators design trials to suit their needs.The best patient is someone who has lots of freetime for office visits and who lives nearby," shesaid. "But that doesn't always represent adiverse group of people." Kumanyika said thatefforts to diversify patient populations such asincluding minority groups, people from differentsocioeconomic backgrounds and women arecrucial.

-- Lisa Piercey Washington Editor

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