FDA Drug Amendments: Still a good fit at fifty?

Fifty years ago on Wednesday, President Kennedy signed into law the US Food and Drug Amendments. The amendments radically overhauled the way in which manufacturers brought drugs to market. Most importantly, the amendments instituted the four-phase review process and the requirement that manufacturers get informed consent from people receiving experimental drugs. If the past fifty years is any indication, though, its unlikely that FDA’s current regulations are well suited to deal with the changing context of medicine, including clinical trials of stem-cell therapies forecasted with the Nobel Prize Committee’s awarding of their prize in Physiology or Medicine earlier this week.

The amendments’ supporters had good intentions and the regulations have had positive effects overall. Yet the US government is still trying to redress many of their negative consequences. The rules have proven to be outmoded for new circumstances that policymakers did not have in mind when they created the amendments five decades ago.

The four-phase review process requires that manufacturers apply to the FDA and submit drugs for agency review three times—at least. One consequence of the four-phase review system is that it extended the time until consumers could access new therapies. This can seem a small price to pay to assure that drugs are safe and effective, a phrase that has become the slogan for the Amendments. People with new, fast-moving diseases, however, have seen the delay as a death sentence. For example, sociologist Steven Epstein has written extensively and carefully about the response to drug delays in the 1980s and 1990s among the HIV/AIDS activist community. The FDA has responded with changes, such as a fast-track approval system, but these shifts tend to come only in response to dire crises.

The four-phase review process has also demanded that manufacturers test drugs on many more people than ever before. Requiring more drug testing and regulating it more carefully also seems like a good idea for the consumer public. Yet the most dangerous studies use people who are certified as healthy and will not get any therapeutic benefit. This requirement of the amendments extended what would seem by today’s standards to be one of the most inequitable recruitment systems into the 1970s: prisoner research. Medical researchers had long done studies in prisons, of course. Yet in the 1960s, research on prisoners exploded in large part because of the amendments—combined with the glut of new drugs manufactured after the pharmaceutical industry took off following World War II. The federal government spent years clearing the backlog of approvals for all of the drugs on the market in 1960s, mostly by using research done on prisoners. By 1972, FDA estimated that more than 90 percent of all drugs were first tested on prisoners, according to Jon Harkness’s indispensable PhD dissertation, Research Behind Bars.

Today, many scholars and advocates believe an equally unjust recruitment system has developed, one that exploits people with low socioeconomic status and people living in countries with poor healthcare infrastructure, including the USA.  Much has been written on this topic ranging from the scholarly to the polemical. A sound and smart starting point in this area would be the work of sociologist Jill Fisher on trials in the American context and anthropologist Joao Biehl’s enlightening (if dense) account of AIDS in Brazil.

The amendments changed consent practices as well. Before the 1960s, researchers themselves were allowed to judge whether people had agreed to be part of medical experiments, and whether they knew enough about the studies to make sound decisions. Some researchers used consent forms to document people’s agreement, but not all researchers did this and certainly not all of the time for all types of studies. For example, as of 1960, NIH leaders refused to change the agency’s policy that stated researchers “may” get signed consent forms from study participants to a policy that researchers “must” get signed forms. (See chapter five of my book Behind Closed Doors for details.) Eventually, the clinical researchers caved in.

Since 1962, though, the length and complexity of consent forms has grown to such an extent that they often defeat the purpose. The point of using consent forms, no doubt, has always been to protect researchers from lawsuits. Still, the additional point for lawyers and lawmakers at the time of the amendments was to use the forms to share information and to keep researchers honest. Today long, verbose forms designed to protect researchers and manufacturers are a poor way to share information with people. To say that a person has given consent has come to mean that she signed a “consent form.” There are more—and more appropriate ways—to exchange information about research than through reading and writing, which dominates the consent process today.

Wednesday is an important anniversary for the FDA because the amendments have brought improvements in review and consent, but they also have an unsettled legacy. In honor of the amendments and the troubled agency, you might check out Daniel Carpenter’s book on the FDA, Reputation and Power, which is encyclopedic and the authoritative source on the FDA. And with clinical trials of stem cell therapies on the horizon, is a good time to ask of any health regulations: When they are no longer a good fit, how is it possible to make them more flexible?

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