Behind the scenes: How a drug becomes a drug

Scientific studies are just one element of the long process that gets a new drug ready for market. Everything factors into a drug's debut, from the medicine's name to an awareness of the disease it treats.

By Victoria Stagg Elliott, AMNews staff. Jan. 6, 2003. Additional information

Advertisements for "Talk IBS," a campaign to inform women about a specific type of irritable bowel syndrome, appeared last month in major newspapers. The advertisements featured a celebrity -- Lynda Carter, television's Wonder Woman -- whose mother had the condition. The ads listed the condition's symptoms, with the tagline: Talk to your doctor.

In the marketing biz, this type of effort is known as "an unbranded educational campaign." "Talk IBS" is funded by Novartis Pharmaceuticals, in the hope that raised awareness of the disease will trigger an increased demand for their new drug, Zelnorm (tegaserod maleate). The medication, approved by the Food and Drug Administration this past summer, is the only treatment for the particular IBS variant targeted. Marketing geared to physicians started in September 2002. But name-specific advertising directed to consumers still won't start for months.

"We're the first product in a new category, so the market has to be educated," said Kurt Graves, senior vice president and general manager for U.S. commercial operations at Novartis. "Your first priority has to be to get physicians comfortable with the product. The second phase is raise awareness and educate consumers about the condition and ask them to go in to see their doctor to get diagnosed. If they are diagnosed with it, the doctor will see if there are any treatments that can help them."

Such efforts are a common practice within the pharmaceutical industry. The plan is usually put into action years before the drug is even approved. And it comes with a price tag in the millions, on top of the investment necessary to research and develop the drug scientifically. But doing it right can make an enormous difference in how the pharmaceutical is received.

Estimates of the cost of drug development including both research and marketing range from $110 million to $900 million per drug. Industrywide, according to IMS Health, a pharmaceutical market research and consulting firm, drug companies spent $19.1 billion in 2001 on promotional activities, including $2.7 billion on direct-to-consumer advertising. This amount is above and beyond the $30.3 billion invested in research.

Ultimately, though, every drug has its own path to market. Some will be blockbusters. Others will fade. Each drug is marketed by a varying combination of targeting physicians and consumers. A need is defined in the phase I trials, and scientists usually begin to have a pretty good idea of what the drug can do. The marketing people, meanwhile, also start trying to figure out if it will sell. Sometimes it's a drug that will do exactly what something else on the market is already doing, but the niche is big enough for a "me-too" drug. Others offer easier-to-swallow therapies or have slightly different actions. Still others treat diseases that never had treatments before.

Research and marketing costs $110 million to $900 million per drug.

"It's possible that very early on the marketing people will say it isn't going to sell," said Mickey Smith, PhD, professor of management and marketing and pharmacy administration, at the University of Mississippi in Oxford. "The marketplace is not ready or it's too crowded. Some drugs are killed that way, and if it's just another 'me too' and they can kill it then, they save everybody money."

In Zelnorm's case, though, the medication is helped by the fact that IBS is a well-established disease. Additionally, Novartis surveyed patients with the disease extensively about their needs and decided Zelnorm could fill a void. But, since no treatment previously existed for this particular form of the disorder, the strategy was developed to address the fact that patients may not know to ask for it.

Other drugs follow a less straightforward route. The blockbuster Viagra started out as a failed angina drug, but turned out to address a very different health problem. Its manufacturer, Pfizer Inc., was left with a drug to treat a disorder that, at the time, no one would talk about that and that occurred in patients who don't generally have regular contact with a physician.

But regardless of the path, one of the early and very important steps is finding a name.

X's, Y's, and Z's

The hunt for a name involves lots of people scouring computer-generated lists of a seemingly endless number of possible choices. Sometimes none get through the rigorous examination.

"That's a painful moment," said George Didomizio, president of Gemini Trademark Services, a Philadelphia drug naming company credited with the names Zocor and Pepcid.

80% of a drug's marketing budget targets physicians.

An ideal name will clear trademark offices in numerous countries without sounding rude or inappropriate in any language. The moniker also won't be confused with others, and the FDA will approve it. Generally, the goal is to pinpoint a branding that will resonate with doctors without scaring patients.

Some handles relate to the disease or to what the medicine might accomplish. Others are linked to the generic name. And sometimes, names have almost no meaning at all.

"Zantac and Prozac are examples of names that have no meaning but they're particularly effective," said Didomizio. "They're easy to pronounce and spell and very protectable by the trademark attorney because they're so distinctive."

Zelnorm was chosen in part because "norm" relates to what the drug is supposed to do -- make a patient feel normal. The 'z' is part of a longstanding fashion trend in drug naming that favors z's, x's and y's.

The entire process takes years and usually starts during the phase II trials. But when the company opts to use this label publicly is a delicate calculation. Use it too soon and face the risk that the drug may fail to get FDA approval. The company then will be wasting a perfectly good name and the hard labor that went into picking it. Wait too long, and the drug will arrive on the market without an audience or a context.

"There's no general consensus in terms of when the brand name should be used," said Jennifer Coe, strategy director for Datamonitor Healthcare, an international market analysis company. "Ideally, it should be as early as possible because, as soon as you start communicating to your audience about your product, you want to be communicating something coherent."

Pens, Post-it notes and freebies

Physicians are no strangers to marketing messages. Drug reps show up regularly at their offices, keeping them supplied in pens and Post-it notes. And, advertisements appear in publications they read, such as this one.

But sometimes the messages are more subtle. Physicians are invited to educational sessions sponsored by drug companies that, even if they do not mention a specific drug -- much like the "Talk IBS" campaign, are designed to increase sales. According to the Society for Academic Continuing Medical Education, more than 40% of funding for continuing education at medical schools is funded by commercial sponsors -- an increase from just 17% in 1994. Drug companies may also fund the development of treatment guidelines. But while many physicians have concerns about these practices, there are few other options. "I have concerns, yes, but alternatives, no," said Dr. Smith. "There's no place else a physician can go. Someone's got to go out there and tell them about this stuff, but no one else is doing it."

More than 40% of CME funding at medical schools is from commercial sponsors.

Increasingly, drug companies also fund much of the research into their products, either by making grants to universities or by owning their own labs. And it is this last bit that is generating controversy. There is concern that these studies may be designed to show drugs in their best light.

According to a paper presented at the American Geriatrics Society in May 2002, drug studies presented at scientific meetings are uniformly positive if research is funded by a drug company. Of those funded independently, one-third were negative.

"It doesn't mean it's invalid," said Chad Boult, MD, MPH, lead author and a professor at Johns Hopkins Bloomberg School of Public Health. "But it should be put in a different context. ... It should be taken with a little more skepticism."

And, although medical meetings and peer-reviewed journals insist that authors make clear their funding sources, this is not always simple. When Dr. Boult was researching his paper, he ran across posters funded by organizations of which he had never heard, only to have the money trail lead to a large drug company. "They were either owned by a drug company or established to serve the needs of a drug company. But you can't really tell right off," he said.

Although 80% of a drug's marketing budget targets physicians, consumers are also targeted with unbranded awareness campaigns as well as direct-to-consumer advertising and money-saving coupons. Drug companies also underwrite disease-management programs and patient advocacy groups.

Novartis, for example, is one of the funders of the Irritable Bowel Syndrome Self Help and Support Group, although a spokesperson from the drug company said it does not try to influence statements from the group. "We never ask them to say anything about a drug because the minute a pharma company asks an independent society like that to talk about their drug, you take away their credibility," said Novartis' Graves.

A changing market

Drug marketing is a reality, and many maintain that it serves an important purpose. But there are also ongoing efforts to ensure it doesn't go too far. The FDA, for instance, regulates direct-to-consumer advertising. However, a General Accounting Office report released in December 2002 found this oversight insufficient. And doctors often become frustrated.

In September 2002, the Dept. of Health and Human Services Office of the Inspector General issued a document outlining exactly what would make a drug company subject to a fraud or abuse investigation. Even the Pharmaceutical Research and Manufacturers of America, weighed in with guidelines on gifts to physicians.

Still, change will likely be dictated by the forces that combine both advances of science and the market. Many believe that what we see now -- blockbuster drugs with multimillion dollar marketing campaigns -- may soon be out of vogue. Over the past months, several consultant firms have advanced the opinion that this strategy is not economically sustainable, and few believe that new blockbuster drugs are on the horizon.

The expected coming of age of pharmacogenomics may also shatter the one-drug-for-many ideal. Instead, the future may be individualized, offering one drug for one person.

"At the moment, you have these blockbusters, but pharmacogenomics is going to dramatically segment the patient population," said Coe. "We're going to be able to target specific segments with a drug that is, hopefully, 100% effective with negligible side effects. The bigger companies will try to own a therapy area. Now, we have Pfizer with Lipitor. Maybe it'll be Pfizer and hyperlipidemia one day, with a whole load of drugs that will treat the various genetic causes of hyperlipidemia. We'll call those drugs multibusters."

ADDITIONAL INFORMATION:

Assisting in the production

As the science behind a new drug advances, so does the marketing strategy. Here's the general timeline:

Phase I clinical trials

Marketing team assembled.
Drug positioning determined.
Will it be a "me-too" drug or treat a disease that never had a treatment before? Does a need exist for it?

Phase II clinical trials

Work begins on the name.

Phase III clinical trials

Name is confirmed.
Marketing strategy for physicians, pharmacists and consumers determined.

Weblink

GAO report (03-177), "Prescription Drugs, FDA Oversight of Direct-to-Consumer Advertising Has Limitations," Oct. 28, 2002, in pdf (http://www.gao.gov/new.items/d03177.pdf)

HEALTH & SCIENCE