Outsourcing Clinical Trials

The high costs of conducting clinical trials in the U.S., the difficulty in recruiting patients, and bureaucratic delays are causing small biotechnology and large pharmaceutical companies to seek clinical trials partnerships outside the U.S. “Over the past few years, there has been an absolute increase in the number of patients enrolled in countries outside of the U.S. and Western Europe,” said Pablo Cagnoni, M.D., senior vice president and global head of clinical development at Novartis Oncology, by e-mail. The reasons, he added, include faster regulatory timelines for approval of a clinical trial, improvement in quality of the investigators, and regulations stipulating that local patients must be enrolled in clinical trials for drug approval. He also noted that developing targeted therapies requires screening many patients to identify the small group with the molecular abnormality of interest. Numbers of patients enrolled in Asia and Eastern Europe have increased especially, said Cagnoni. “In Japan, for example, the government has taken steps to align their requirements with those of other countries. We have increased Russian participation due to the need to include local patients for [drug] approval in Russia.” The Chinese Example The boom in clinical trials has perhaps been the biggest in China, owing to improvements in the medical infrastructure there. “China’s health care market is now $50 billion USD and growing at a rate of 30% a year, which will be $600 billion in 2020,” according to Lan Huang, Ph.D., CEO of Dalian Wanchun Biotechnology in China. “As of November 2010, 57 global phase III trials were being conducted in China, with companies such as GlaxoSmithKline, Bristol-Myers Squibb, and OSI Pharmaceuticals testing cancer drugs. A large amount of private investment also supports innovative drug development.” A cancer researcher trained at the University of California, Berkeley, with a postdoctoral fellowship at Memorial Sloan– Kettering Cancer Center, Huang returned part-time to her native China 10 years ago to do drug research and development and cofounded several pharmaceutical companies. She began her China–U.S. partnership when the cost for an early phase I/II clinical trial of her drug for brain cancer was $100,000 per patient in the U.S., compared with $10,000 in China under the same protocol. “The U.S. has very good drug discovery powerhouses that know clinical trial design,” said Huang. “In China, we can use clinical protocols from the U.S. to study a drug by looking at many indications in parallel rather than sequentially. Drug development costs are reduced by China’s lower medical costs: 20%–30% of those in the U.S. The time to trial completion is faster because the large clinical population speeds enrollment.” She said that patients have the incentive of free clinical trial drugs, which China’s universal health care coverage, capping at $300 per year, does not reimburse. Huang said their advantage begins at the preclinical level with a molecular diagnostic analysis of each person’s tumor. “Our highly trained researchers have access to large numbers of tissue samples, many from untreated patients, that we use to identify the right people to test for a drug. With higher success rates in early phase I/II trials, we then do trials on promising drugs in the U.S.,” said Huang, who received the Thousand Talent Innovator Award from the Chinese president. But, she warns, not every pharmaceutical company can expect a welcome in China. “The Chinese government does not like companies to use Chinese patients as testing subjects, and China is very serious about patent protection.” Her company is partnering with Nereus Pharmaceutical, a California company focused on developing anticancer rating means they believe “there is a moderate or high certainty that the service has no net benefit, or the harms outweigh the benefits.” Other major international health organizations have similar reservations or recommend no PSA screening. Most groups indicate that screening to determine who should undergo prostate biopsy typically includes both a serum PSA and digital rectal examination, with the latest American Cancer Society publications noting that the rectal exam is optional. All groups recommend an informed discussion with patients and state that screening does not increase the number of men diagnosed with nonmetastatic, early disease that may not prove lethal. Gomella said this latest study led by Loeb could work in favor of PSA screening, partially because the researchers looked at a large group of men while focusing on multiple changes in PSA level. That this latest study resolves the PSA controversy and satisfies USPSTF is unlikely, however. “It’s going to take a lot more data sets to confirm these findings,” said Carter, adding that the PSA is a great test that has been used incorrectly. “There is strong evidence that PSA testing has saved lives, but too often we screen the wrong age groups. We’d be much better off if we screened the younger men who are more likely to benefit, rather than just older men.”