"In response," says Ebeling, "we educated patients that they should explain all their symptoms to their doctor. And we educated physicians that the disease is really bothersome and when patients present with pain only, they should explore other symptoms and not wait until patients describe them."

But perhaps the most ambitious example is Novartis' "Take Action for Healthy BP" program, which aims to educate consumers about blood-pressure control. "In hypertension, we were always struggling with two issues," Ebeling says. "Why don't more patients seek treatment? And why are patients not complying, when hypertension can result in severe health issues?

"We found some funny insights. For instance, most baby boomers believe they are 15 years younger than they really are. Patients often respond with denial when diagnosed with hypertension—they think diet and exercise will do the job. And physicians don't realize that when they titrate a patient up, most patients regard it as treatment failure."

"We're helping the physician manage the patient better so the patient is more compliant," says Ebeling. "Patients are still not as motivated to treat hypertension as other diseases, but we have seen fantastic success and we will continue to learn."

The Grammar of Discovery In recent years, Novartis has invested heavily in research and development—R&D spend topped 19 percent of sales in 2003. Part of the investment has gone toward a new global headquarters in Cambridge, Massachusetts, for the company's research operation, Novartis Institutes for BioMedical Research (NIBR). Two state-of-the-art buildings are now opened and staffed. The first, a 255,000-square-foot facility in Technology Square, opened in March 2003. The second, a complete renovation of the 500,000-square-foot NECCO candy factory, opened in April 2004. The facilities together will house 1,000 scientists, one-third of Novartis' global research team.

NIBR's president is Mark Fishman, a cardiologist and long-time Harvard professor. As Fishman immersed himself in the question of how to make drugs, he was struck by the need to balance short- and long-term goals. In the long run, he says, the aim is to fundamentally change what he calls the "grammar" of discovery. In the short term, the question is how to reduce risk. "Typically when companies look at risk, they're thinking financial risk," Fishman says. "The idea is to get products in large markets that can yield high sales."

Fishman was thinking more of scientific risk—looking at how well disease processes are understood to assess the chance that the company will successfully treat the condition. "This wasn't the way decisions had traditionally been made in pharma," he says. "One thing you notice, though, is that the newer the drug, the grosser the misestimates of markets. Think of cholesterol drugs, which were expected to be a small market."

Fishman created a simple matrix. One axis asks whether the drug meets an unmet need, the other, "whether the company has a scientific crack at it," Fishman says. "If you stick in the upper right-hand quadrant, you reduce risk." Fishman made all his researchers use the matrix to argue for their projects. "It immediately cut 30 percent of the projects," he says.