Contract Research Organizations Help Guide Compounds To Approval

These days, many biotechnology and pharmaceutical firms facing the daunting road to market with a new drug are opting to get help from contract research organizations, or CROs. These service companies specialize in providing all or part of the necessary clinical trials; they also manage regulatory reviews. And their participation in the drug- development process is growing dramatically as the number of candidate compounds coming through the so-called research pipeline climbs. "Many biotech companies don't have the capabilities to do this kind of drug development," says Sara Creagh, an executive vice president with Quintiles Transnational Corp., the parent company of Quintiles Inc., a fast-growing CRO. Both are headquartered in Research Triangle Park, N.C. "Many times, even pharmaceutical companies don't have those capabilities, but little biotech companies--the new ones, the emerging ones--certainly don't." As the growing use of CROs enhances the commercial prospects for organizations, it is improving the career outlook for many individuals, as well, since--for scientists with Ph.D.'s in fields such as immunology, pharmacology, biochemistry, and physiology who also have clinical experience--the expansion of these companies represents a burgeoning area of new job opportunities. Fueling growth in the CRO sector is the enormous productivity of basic researchers at biotechnology and pharmaceutical companies, which has led to a steadily growing number of candidate drugs. It is the hoped-for result--a fully developed, profitable product--that is crucial to keeping the company afloat and its discovery- oriented scientists at their benches in the future. "That's key," says David Stump, senior director of clinical research at Genentech Inc., based in South San Francisco, Calif. "It's the business weUre in. If you're not developing drugs, all the elegant research in the world won't take you anywhere." He adds: "We're using biotechnology to produce breakthrough products. In order to clearly show that we have a breakthrough product, we have to show that it does something important in patients with disease. And the whole process has to work, from discovery to development to marketing." While recognizing the need to develop their innovative compounds in order to survive, many biotechs, especially smaller companies, may be reluctant to hire the staff necessary to plan and manage the full-scale safety and efficacy trials regulators demand. "They don't want to throw their money into building the infrastructure to develop their drugs," says CRO executive Creagh. "They want to create the drug, and then let the clinical development happen somewhere else. [CROs] let them put their resources into what they do best. A simple way to look at it is that they focus on the R in R&D, and we do the D." Among the leading CROs, in addition to Quintiles, are G.H. Besselaar Associates, Princeton, N.J.; IBAH Inc., Blue Bell, Pa.; PAREXEL International Corp., Waltham, Mass.; and Pharmaco LSR in Austin, Texas. Besselaar, the oldest and best established of the CROs, moved from small-scale consultancy status to being a full-fledged CRO in the mid- 1970s, according to CRO executives. The others grew substantially in the mid- to late 1980s and the beginning of this decade. In 1993, pharmaceutical and biotechnology firms spent about $25.6 billion on R&D, according to one industry estimate, of which approximately $17 billion went to clinical drug development. Of this amount, CROs claimed about $3.5 billion. Current annual growth rates at several leading CROs are estimated at between 20 and 30 percent by company officials. In addition to sparing the sponsoring company much of the work of drug development, CROs bring other advantages. Through specialization, they often possess clinical expertise the sponsor may not, which they are able to translate into streamlined protocol designs, efficient data collection and analysis, and complete regulatory-submissions packages, thereby shortening the overall time needed for development. With the average time needed to bring a new drug through the development process to market in the United States currently estimated at more than eight years--and with a drug's patent protection at a mere 17 years--this time saving can be critical. Moreover, industry observers point out, the pharmaceutical market today is international, requiring that sophisticated trials be designed that will be able to satisfy regulators in, say, Japan, Australia, North America, and Europe simultaneously. "There was a time five years ago when you'd do one development in Europe and you'd do one in the U.S.," notes Helen Davies, an M.D. who heads the clinical operations group at Quintiles. "Now, you do one drug development for a regulatory-submission package across the world." The larger CROs can conduct full-scale clinical trials from start to finish if asked to do so--designing the trials, recruiting investigators, managing data collection and analysis, and dealing with regulators--but this is not the only working model. The sponsoring company may want to plan and direct the entire campaign, using the CRO only for logistical hiring support. Or the company may need help with only one aspect of the process, perhaps the regulatory review phase or the more complex Phase IV trials. "The client doesn't say, `Here's a vial of white powder; call us when the drug's approved,' " says Jeffrey Lazar, an M.D. with a Ph.D. in pharmacology who is executive vice president at Pharmaco LSR. "It virtually never works like that now, although things are changing. A company may have a very rich pipeline, with more compounds than it can deal with. Its senior scientists are managing the development, but what they need are field extensions. So, they come to us for trial monitors or project managers." Genentech, for example, uses CROs in this way, seeking outside help with development while retaining ultimate control of the process. RWe use CROs for the tactical side of this much more than for the strategic side," says Genentech's Stump. "We believe strongly that our clinical scientists and our internal regulatory staff should take the lead in designing the trials, plotting out the developmental strategy for which trials will be done, when they'll be done, and where they'll be done. We'll then use a CRO as a tactical extension of us, for doing the work. "We have to have ownership of the strategy behind the process," he adds. "We've invested a lot into every product by the time it ever comes to clinical trial, so, we take a very active role." "We use [CROs] because we don't have the resources at a given moment to carry out our functions," says Richard Devlin, an immunologist and director of clinical research operations at Genetics Institute, based in Cambridge, Mass., "either because we have so many other projects--that's typically the case--or because we don't want to staff up for a project only to then have personnel on board that we might not need for some other project." The need in the biotechnology and pharmaceutical industries for clinical researchers to design and manage trials and to shepherd regulatory submissions is expected to grow vigorously in the coming decade and beyond. At the same time, many of these companies have gone through recent cycles of downsizing, mergers, and layoffs, trimming their clinical personnel sharply in some cases. CROs are growing sharply in response to these moves, as is their own need to add new scientific and medical staff. "It's certainly a growing area," Quintiles' Davies says. "The Ph.D.'s tend to go into our medical and regulatory groups where they work on strategic-development plans and writing of final reports. And then we have a large statistical-analysis group." Biological scientists with statistical training are especially in demand at the CROs, because of these researchers' crucial role in interpreting clinical data. "Biostatisticians have a very important role in drug development, and we have a large biostatistics department," says Pharmaco LSR's Lazar. "Although all of us would like to think that a drug either works or it doesn't--it lowers blood pressure or it doesn't--life is, unfortunately, not that black-and-white." Typically, after the discovery of a new compound and preclinical laboratory and animal studies to show its safety and biological activity, a company will file what is called an investigational new drug (IND) application with the Food and Drug Administration (FDA). Unless FDA raises objections, Phase I human clinical trials can begin 30 days later. In these trials, small numbers of healthy volunteers, usually fewer than 100, help to assess basic safety and dosage levels. In Phase II trials, groups of 100 to 300 volunteers- -often with different illnesses or conditions--are given the new drug to determine target diseases and generate early data on effectiveness, safety, and dose-response curves. Phase III trials may involve thousands of volunteers, some healthy and some with the target disease or condition, in double-blind and placebo-controlled studies to establish clinical evidence of efficacy and safety. If all goes well, a new drug application (NDA) to FDA follows. Even if the drug is approved for use at this stage, Phase IV trials may yet be required to assess the drug's ongoing performance in actual patient populations. --Franklin Hoke

Contract Research Organizations Help Guide Compounds To Approval

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