There’s no denying that cancer treatments keep getting better, thanks in large part to ever more sophisticated and precise drugs that can target tumors exquisitely and eliminate them before they spread and cause serious disease.
The reason has to do with the many ethically questionable practices throughout the drug-development process, says Peter Wise, retired from Charing Cross Hospital and Imperial College School of Medicine in London. These practices range from research by pharmaceutical companies to the way new compounds are tested, how data is interpreted, to the approval process by regulatory agencies and the way that doctors are incentivized to prescribe them. “There are different layers in the whole process and real problems all the way down the line,” he says.
For example, drugs used to be tested in academic centers by faculty researchers who were independent of the companies that developed them, and therefore were more likely to have unbiased perspectives in analyzing the data. But many are now tested by contract research organizations hired by pharmaceutical companies to conduct the trials. Because they are beholden to the companies, these groups may introduce biases in interpretation of their results, says Wise.
More important, the way trials are designed has changed considerably. Traditionally, scientists would evaluate new drugs based on how much they improved the death rate from disease. Now so-called surrogate endpoints — such as how the agent affects tumor growth or levels of certain tumor-related proteins — are used as ways to validate the effectiveness of a new drug. If approved, doctors and patients still don’t know for sure whether the drug will actually lengthen lives and improve their survival.
Regulatory agencies also perpetuate the problem when they accelerate approval for medications, allowing such surrogate endpoints in an effort to telescope the process rather than requiring that studies continue until data on survival can be collected. A Food and Drug Administration analysis in 2010 found that 45% of cancer drugs awarded accelerated approval failed to earn full approval, either because their early results proved untenable or the companies failed to provide the required additional data to support their application.
Even doctors aren’t immune to the bias, because once a drug is approved, pharmaceutical companies launch aggressive campaigns to educate and persuade doctors to prescribe their product.
For the patient, this means that more drugs that offer only marginal benefit, such as a two-to-three-month longer survival, are flooding the market. That’s especially worrisome, since a study found that 75% of people with advanced colon or lung cancers believed that the chemotherapy treatment their doctors offered would cure them, an unrealistic belief not supported by any science. Wise says that patients need to be fully informed of what benefits new cancer drugs can provide, and doctors need to ensure that their patients understand the medications may provide only a marginal improvement over traditional therapies.
What could be more helpful, he argues, is if doctors give patients more opportunities to participate in clinical trials, rather than directing them toward new drugs that might only give them a few more months. Because trials often compare new agents with existing standard therapy, people who enroll will be, at the very least, receiving the standard of care. And the more information such trials generate about the effectiveness of new drugs, the less likely it will be that current unethical practices continue. At the moment, only about 3% of adult cancer patients participate in clinical trials. “If more patients enrolled in clinical trials, there would be quicker recognition of whether the drug being tested is a good one, and it would save the country money in health care costs,” says Wise.
More consideration also needs to be given to the option of forgoing drugs as well, especially if they will only provide little benefit for people whose cancer is essentially untreatable. It’s a more controversial view, but one that Wise says would allow more people to enjoy their final days with family in their own homes and not in a hospital weakened by an ineffective treatment. “Patients need to be counseled about options and not just given willy-nilly cancer drugs because that’s the knee-jerk reaction,” he says. “That has to stop.”