Trials and Medications

By Bednar, Joseph

When newspaper headlines trumpet the ‘next big thing’ in medicine, consumers – especially those struggling with cancer or other difficult-to-manage diseases – eagerly await the product’s debut on pharmacy shelves.

As doctors weigh the benefits of each new offering and patients anxiously ask questions, the pharmaceutical company that developed the drug is wrapping up years of research, tests, and marketing, all of it necessary to bring about a successful product launch.

The U.S. Food and Drug Administration (FDA) demands a rigorous regimen of testing for any new product a pharmaceutical firm wants to bring to the marketplace. The FDA oversees a wide range of consumer products, and while some, such as cosmetics and dietary supplements, may usually be marketed without prior approval, drugs and many medical devices must be proven both safe and effective before companies are permitted to market them. The higher the risk to consumers, obviously, the more rigorous the approval process.

Each FDA decision on a proposed drug includes a judgment about whether the new product’s benefits will outweigh its risks. The FDA might allow a product to present a certain risk when its potential benefits are greater, particularly in the case of medicines used to treat serious, life-threatening conditions.

“Generally, if it’s not a brand-new cure, they won’t speed things up, but there have been cases with an earth-shattering breakthrough when, yes, the FDA will give it priority and try to expedite its approval,” said Fletcher Nehring, pharmacy clinical coordinator at Mercy Medical Center. “But those cases are rare.”

To make those judgments, the agency – which does not test products itself – relies on the initial clinical tests on animal and human cells, as well as the pivotal, required series of human tests. Once these trials have been completed and the data has been presented, it is not uncommon for a new product to be introduced into the marketplace within six months of the start of the FDA’s review.

In this issue, BusinessWest takes an indepth look at the process of taking a new drug from the laboratory to the corner pharmacy.

Lengthy Process

Long before testing may begin in humans, a drug must undergo testing in animal and human cells or possibly in animals – and this early research can last for years. If these tests are deemed successful, a firm then issues an investigational new drug application to the FDA, requesting approval to begin tests on human subjects. Those tests, if approved, consist of three phases. If the FDA grants what is known as a new-drug approval, the company then conducts a final round of post-marketing tests once the drug has made it to the marketplace.

The Phase 1 tests focus primarily on a drug’s safety and naturally involve the fewest test subjects – usually a group of 20 to 100 people who are paid for their participation. Researchers try to determine the effects of the drug on the human system, and they examine the development of side effects as dosage levels are increased. More than two-thirds of experimental drugs pass this initial round of testing, which normally lasts a few months.

“Phase 1 is the smallest population of people tested, basically for safety,” said Nehring. “It’s the first time a human has the drug administered, and these patients don’t necessarily have to have the disease it’s treating; it’s just to make sure it’s safe.”

In phase 2, which can last from a few months to two years and might involve several hundred test subjects, the drug is tested for effectiveness. Many phase 2 studies are randomized trials, meaning that one group of patients will receive the experimental drug, while a separate control group receives a different treatment or a placebo. Sometimes these are double-blind studies, with neither the researchers nor the volunteers knowing who is receiving the actual drug.

Of all clinical trial drugs, only about one-third make it to phase 3, which is a large-scale test involving several hundred to several thousand patients. This larger group will provide the best information about the range of a drug’s effectiveness, benefits, risks, and side effects.

“In phase 2, they actually give it to patients with the disease,” Nehring said. “It’s a bigger group than phase 1, and they actually start to look at the effectiveness of the drug. In phase 3, it’s an even bigger group, and this tests both safety and effectiveness. They hone in on the perfect dose and how to get the most benefit for the side effects.”

Many of these studies are also randomized, with both parties blinded to who has received what treatment. After what is sometimes several years of testing, between 70% and 90% of the drugs that make it to phase 3 successfully complete the phase and move on to a request for FDA approval.

The Final Stages

Pharmacists say the FDA looks for products that meet what is known as the ‘gold standard’ for a specific treatment. In other words, the agency wants new treatments to match a certain level of effectiveness that has been demonstrated by existing products, with a minimum of risks and side effects.

After the first three phases of study, the FDA will decide to label each proposed new drug a standard review or a priority review.

The drugs given priority status are the ones perceived to have a significant impact on a disease, while a standard review is given to a new drug in its category that doesn’t represent any blockbuster advances in treatment.

Drug developers also fund studies of their proposed drugs that are often published in leading medical journals in an effort to spur interest in the medical community. Some physicians don’t bother with such drug company-sponsored reports, while most base their judgments on their own previous experience with particular drugs and particular companies.

If a new drug is approved by the FDA, it enters the marketplace, and the final, post-marketing phase of studies begins. During these studies, pharmaceutical companies aim to compare new drugs with existing medicines in the marketplace and test the new drug’s long- term effectiveness and impact on patients. In addition, these studies often aim to determine the cost-effectiveness of the new treatment compared with other treatments available.

“The fourth stage is post-marketing surveillance, where the company will continue to gather information about any additional side effects,” Nehring said. “Phase 4 is important; we’ve seen drugs like Vioxx and others get withdrawn from the market after the FDA approved them.”

At this point, drug companies are also busy communicating the value of their new products with television, radio, and newspaper ads – a direct-to-consumer marketing tab that adds up to more than $4 billion per year across the industry, up from $700 million in 1997.

That figure has led some in the medical field to complain that pharmaceutical companies, by drumming up hype for their own products, are creating markets for their medicines that don’t need to exist, feeding a culture that already takes too many pills. And when that $4 billion figure is combined with the cost of free samples, more than 110,000 sales representatives in the field, and other efforts, the total annual cost of drug-company marketing has been estimated at more than $30 billion.

Clearly, with the number of years and dollars pharmaceutical companies invest in taking proposed treatments through all the required phases for FDA approval, the financial stakes are high for drug makers. The rigorous approval process put in place by the FDA aims to ensure that the equally high medical stakes are not ignored.

Copyright BusinessWest Jul 7, 2008

(c) 2008 BusinessWest. Provided by ProQuest Information and Learning. All rights Reserved.