Knowing site metrics will help you stay competitive as industry changes

Drug industry should focus on efficiencies

The pharmaceutical research industry's productivity is declining and cost is rising, a dangerous combination that is the force behind changes in how drug company sponsors do research.

There has been a steady decline of new drug applications (NDAs) since the mid-1990s, says Ken Getz, MBA, MS, a senior research fellow at the Tufts Center for the Study of Drug Development at Tufts University in Boston, MA.

"At the same time [drug development] cost has been rising at 11.2% annually for the past five years," Getz says. "That's a dangerous combination."

Normally, if costs are rising then it might indicate that the industry is optimizing drug development activity, Getz explains.

"The expanding volume and scope of activity is a driver of higher cost, but there's no guarantee that the increased volume and scope will translate into higher success rates," he says.

As a result of these trends, pharmaceutical companies are conducting more clinical trials, and they've become much more global in scope, Getz says.

"About 50% of Food and Drug Administration-regulated trials are out of this country in the next couple of years," Getz says.

"One of the major factors that enticed companies to consider globalizing drug development activity was the cost saving and speed associated with conducting studies in ascending markets like Central and Eastern Europe, China, and India," Getz says. "Historically, those are places that offer cost benefits and, typically, more rapid enrollment speed."

However, there are drawbacks to globalizing drug development. "Over time, companies have come to realize that the more global you make your studies, the more complicated they are logistically, and it can add a layer of inefficiency or difficulty to optimizing your development program," Getz adds.

Clinical trial sites in the United States face the same challenge of rising costs, as well as increased competition. But they can make themselves more attractive to drug company sponsors through consistently meeting enrollment deadlines and producing quality work, experts say.

"I believe clinical research organizations [CROs] and other organizations recognize quality," says Nathan Segall, MD, principal investigator and founder of Clinical Research Atlanta of Atlanta, GA.

The key is for both sponsors and clinical trial sites to capture metrics or data that show how well sites perform with regard to enrolling participants and meeting quality indicators and deadlines.

"The elements of quality have to do with the work and oversight of evaluating the clinical data captured in source documents and subsequently implementing them," Segall says. "Then [sponsors] are able to gather metrics and rate sites according to how well they've done and how they're doing now."

Since about one-third of sites enroll no participants, these metrics are an important way to improve efficiency and reduce drug development delays, Segall adds.

The Tufts Center for the Study of Drug Development identifies the top-performing drug developers over a five-year period.

"In every five-year period we looked at, the fastest companies have changed," Getz says. "That tells you a little about the volatility of the environment." But in the latest five-year period, the fastest companies enjoyed a 17-month speed advantage over their peers within a given therapeutic area, Getz says.

"Not only that, but they're getting faster relative to a median benchmark for the industry," Getz says. "So from 1995 to 2000, they enjoyed a 10-month speed advantage, versus a 17-month advantage they enjoy now."

Merck & Co. is one of the top performers for the most recent period of 2000 to 2005, Getz says.

Merck owes some of its recent drug development success to its relationships with investigators, regulatory agencies, and medical societies, says Ernesto Aycardi, MD, senior director of worldwide research operations at Merck in Rahway, NJ.

Research sites that are interested in conducting clinical trials for Merck should be objective and transparent on what they can deliver with regard to the number of patients and cycle times, Aycardi says.

"Of the same importance, sites should have specific, well-documented site processes that are proven to be effective and consistent," Aycardi adds. "Having dedicated and experienced staff to support clinical research efforts is also critical."

Clinical research sites also need to stay informed about industry trends, especially while the industry is rapidly evolving.

For instance, although globalization is a current trend, there already are signs of fatigue.

While many sponsors claim they're seeing the benefit of moving trials overseas, they're also tempering the perceived benefit with some of the realities and challenges that global programs present, Getz notes.

"They're still doing it, and they want to increase the amount of activity going overseas, but they have a more realistic view at this point," Getz says. "There's not as much hype as it used to be."

While trials conducted globally have the short-term benefit of offering a lower cost and higher enrollment speed, there are potential problems over the long term, he adds.

"They may enroll patients who are not as representative as the American population, for example," Getz says. "And that could be a scientific problem later, and it could translate into marketing issues."

Getz provides this brief look at other current trends in the drug development industry:

Scope of drug development is expanding: "Companies are chasing much more difficult chronic illnesses today that have endpoints that are more difficult to demonstrate," Getz says. The illnesses have longer time horizons for disease progression, he adds.

"We've also seen a huge shift from traditional small molecule candidates to biologics, and biologics by their nature tend to take longer to develop," he says. "So we've seen the influx of biotech companies and pharmaceutical companies getting into biologic-derived compounds from living compounds."

These factors add another layer of inefficiency to the drug development timeline, Getz says.

Since many of the biologics are targeted for specific uses, this requires a larger number of clinical trials that are spread out geographically. There will be fewer patients in each site, and the eligibility criteria are tighter, he adds.

Decline in success rates of new compounds: "We're seeing a decline in the success rates of compounds moving through development … because these are much more difficult chronic illnesses," Getz explains.

"It's harder to demonstrate efficacy and safety," he says. "Part of the view is that we've entered a new realm where we're dealing with more complicated illnesses and more complex drugs."

Many experts think this signifies a major shift in the composition of the drug pipeline and the nature of drug development, Getz says.

Companies make slow decisions to kill less-promising candidates: Pharmaceutical companies are making very slow decisions about killing the less-promising candidates in their pipelines, Getz notes.

"It may not be that different from before, but when you look at the high cost of delays today and look at the typical drug and performance in the marketplace, there's a real opportunity cost for companies," he says. "It costs an estimated $40,000 per day to manage a typical program, and it means $1.3 million in lost sales for every delay."

Sponsors could cut costs and more efficiently allocate their resources if they quickly abandon the less-promising drug candidates and focus more attention on those that likely will make it to market.

"What we've shown is it takes organizations so much time to terminate a candidate that it is often in the most expensive phase of research, the phase III trials, when they determine to terminate it," Getz explains. "There are a lot of resources that went into phase I and phase II."

Although it often takes a large patient population to determine whether a product is working, there are study designs that might provide signals in phase II studies about whether a new product is a "go" or "no go," Getz says.

There's no improvement in regulatory cycle time: The regulatory cycle time is getting worse, if anything, he says. This particularly true of the FDA, Getz adds.

"The IRB cycle times have gotten faster, but the benchmark regulatory cycle time for the most part has risen by about 12 months," Getz says.

"There's a lot of speculation that it has to do with a more skittish regulatory agency," he adds. "This is a tough and critical climate of the FDA, and I think the FDA is quite nervous about how it is viewed and the kind of scrutiny that it's being put under right now."

The top-performing sponsors improve the regulatory cycle time by interacting proactively with regulatory agencies, Getz notes.

High prevalence of inefficiencies in study conduct arena: "Sponsors are desperately looking for ways to optimize drug development," Getz says.

"Site selection and the study initiation process are two of the most inefficient activities today," Getz says. "It takes a long time to engage sites, and 30% will under-perform."

Lately, industry experts have criticized the pharmaceutical company practice of returning to under-performing sites, evden if they never enrolled a single patient in the last trial.

It would be more efficient if sponsors used metrics to help them predict how well a site will perform and to better manage the site's performance, Getz says.

Some of the top-performing sponsors are doing exactly that, and their success has shaved considerable speed off the drug development timeline, he adds.

"Their speed is not correlated with poor quality or higher costs," Getz says. "These companies maintain that standard of quality and contain costs, and they embrace speed practices at all levels of the organization."