Dr. Tim Crater in US News & World Report
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Inside the Clinical Research Machine
Doctors involved in clinical research share why it’s so expensive and why they get involved.
To develop a drug and gain approval from the Food and Drug Administration, it costs about $2.6 billion.
By Lacie Glover Jan. 26, 2015 | 9:25 a.m. EST + More
Pharmaceutical companies have their share of critics, mostly because of the cost of the drugs they make. And prescription drugs – which most Americans take – are much more expensive in the U.S. than in other countries, by as much as 40 percent.
That’s partially because American pharmaceutical companies are allowed to set their own drug prices. In most other countries, governments negotiate prices with the companies and cap the cost of medicines.
But that’s not the only reason drugs in the U.S. are so expensive.
It costs about $2.6 billion to develop a drug and win approval from the Food and Drug Administration, according to a November 2014 report from the Tufts Center for Study of Drug Development. Pharmaceutical companies pay that money up front, and part of the reason they charge so much for drugs is to recoup the investment.
Here’s why it costs so much, and why physicians get involved.
According to the Tufts report, increasingly complex clinical research is responsible for the hefty drug development price tag, and industry experts agree. “Every level of research is expensive,” says Marie Csete, the chief scientific officer of Huntington Medical Research Institutes in Pasadena, California.
As the drug moves through the research pipeline, efforts are increasingly expensive, Csete says. Before drugs are ever tested on humans for safety and efficacy, they must first be discovered and then often tested on animals – both expensive processes.
By the time a drug makes it to a human subject, millions of dollars have already been invested. “Human studies are the most expensive and often must include hundreds or thousands of subjects,” Csete says. “It all adds up, and many drugs fail only after millions of dollars are invested.”
Perils of Human Clinical Research
Human clinical research has four possible phases, and drugs must go through at least three of them to get to market. Phase I studies only seek to determine toxicity at various doses in healthy subjects. As such, they’re difficult to enroll patients in, says Cary Presant, an oncologist at the City of Hope National Medical Center's cancer center in Southern California, where he conducts research trials. “These trials may not give a high enough dose of a new drug to a patient, so patients are sometimes reluctant to enroll,” he explains.
Only after the drug passes Phase I trials can it be tested to see if it works, so these trials are crucial but can be a bottleneck in the road to approval.
Phase II studies determine efficacy of a drug, while Phase III trials are the largest, including hundreds or thousands of patients. Phase IV trials only occur after a drug has achieved FDA approval, and are usually conducted to prove superiority to another drug. Since Phase II and III trials must compare the drug to existing alternatives, patients enrolling in these trials run the risk of receiving placebo or previously approved drugs.
Taking an approved drug is usually preferable to taking a placebo, but many patients enroll in trials in the first place because existing options have failed.
“These patients want to receive the new drug,” Presant says. So patients considering those trials should ask about switching treatment if they don’t do well, he says.
Subject Safety and Protection
If a patient doesn’t do well in a trial, he or she usually has several options. In clinical research, nothing is more important than patient safety. In fact, most pharmaceutical companies and their contractors require research staff to have good clinical practice certifications on top of other ongoing safety trainings.
“Trial subjects may actually be safer than other patients,” says Timothy Crater, a research physician at Hutchinson Clinic in Hutchinson, Kansas. “They see a doctor more regularly and are followed very closely.”
Third parties, called contract research organizations, are hired by the pharmaceutical companies funding the research to oversee the trial in minute detail. CROs also often provide laboratory services and materials to research centers. But as objective third parties, their most important function is preserving subject safety.
“There is an enormous amount of work involved,” says Jeffrey Spaeder, chief medical and scientific officer at Quintiles Transnational, a top CRO. He oversees and makes high-level medical and ethical decisions in trials. “It is a heavily regulated field; there are all sorts of audits.”
This includes FDA inspections to research sites and audits by the CRO and pharmaceutical company, or sponsor.
Another organization, called an institutional review board, serves only to protect subject safety and privacy and to document serious adverse events and privacy breaches. IRBs do not assist in actual operations of the trial like a CRO might; instead, they help ensure everything is on the up-and-up.
The result is an extensive network of checks and balances built into the research infrastructure. Extensive, that is, and expensive. By the time the clinical trial data is presented to the FDA for market approval, thousands of people and billions of dollars have been involved in the development of a drug.
And it still might fail.
Most physicians don’t get involved in research, either because of the amount of work involved or all the money involved.
But that’s not true for everyone.
“I was led to do clinical research by my hope for patients to live longer and be happier,” Presant says. He adds that a commitment to science and patients was always a driver.
“As clinicians, research brings back that sense of wonder, like you can see around the cutting edge to what comes next in medicine,” Spaeder says. “You feel like a pioneer.” And stronger than that, he continues, is the sense that this work is helping people. Others agree.
“I tell these patients they have the opportunity to be a part of something big, and it can help a lot of people down the road,” Crater says. “You wouldn’t expect it, but that’s been the clincher.”
Csete says this also rings true for many patients she sees. “This is a very powerful motivation for participation in research,” she says. “I have seen many critically ill or dying patients determined to make a difference for others that follow them – by contributing to knowledge.”