Help Us Help Others:

A Look At the Drug Approval Process

Getting a drug approved for human use is a multi-step process. First companies must identify a compound that scientists think shows promise and which might alter human biology in some way. These compounds usually come from plants or animals; venomous creatures are a constant area of focus because anything that alters biology (like snake venom) might be tweaked to do something useful as well.

The pre-clinical phase of drug testing

Once a company thinks they have a promising compound, the first step is to test it in animals or study what it does in cell cultures. Usually this involves mice or rats, but it may also be stepped up to other primates like monkeys as the testing comes along. These tests may be used to establish a foundation for the drug, but usually the primary purpose is simply to study its safety. Once a drug has been found to be reasonably safe in animals (i.e., the rats don’t die or show any other obvious signs of problems), the company will then take this data and submit an application to conduct human testing. This application is seldom denied.

The different phases of drug testing

Phase 1: Safety testing

Once approval for human testing is granted, a company will arrange a series of trials. The first phase typically involves giving the drug to a set of healthy volunteers in order to establish safe dosage levels and weed out any serious side effects. (The exception is cancer and HIV drugs, which even in phase 1 are tested upon people who have the disease.) So long as the volunteers don’t die or grow a third set of antlers, the drug moves on to phase 2.

Phase 2: Testing efficacy

The second step is to gather a set of patients who have the condition – anywhere from a dozen or so to as many as several hundred – and give them the drug at various doses to see if their condition improves. This is usually tested against a control group, but the conditions are far less scientific than in phase 3.

Phase 3: Clinical trials

The last step of the process involves administering the drug at recommended doses (which were established in the first two phases) to a much larger group of patients under what are supposed to be much more controlled conditions. These are the bread and butter studies that the company will submit for FDA approval. They almost always involve a comparison group that is given a placebo. If a drug shows any type of improvement over a placebo, it is likely to be submitted for FDA approval.

The FDA review & approval process

The final step is to submit this data for the FDA review. If you’ve successfully demonstrated that your drug seems to help people and is reasonably safe, you’ll receive approval to market your drug for that condition. (Doctors, of course, can then prescribe it however they’d like.) Companies must show the drug effective against either…

  1. A placebo
  2. Another approved drug
  3. The consequences of no treatment
  4. Historical data about the progression of illness without the use of the drug in question.

(Hanson et al., 2004, p. 89)

The FDA employs 18 different advisory committees of outside experts (many of which have ties to drug companies) to help review the application and decide whether or not a drug should be approved. Companies must submit 2 placebo-controlled trials showing a positive effect, even if a drug showed no effect in several other clinical trials. Companies are required to submit results from every clinical trial it has conducted, but how often this actually happens is uncertain. Given the record of the industry, I would be very surprised if this is adhered to on a consistent basis.

There are many inadequacies in this review and approval process. As Sharon Begley states, “The FDA requires two well-designed clinical trials showing a drug is more effective than a placebo. That’s two, period – even if many more studies show no such effectiveness. And the size of the ‘more effective’ doesn’t much matter, as long as it is statistically significant.” (Begley, 2010, p. 37) This leaves plenty of wiggle room for drug manufacturers and creates a climate that favors approval.

The second big issue is that the studies submitted for approval often aren’t large enough to provide meaningful data on the true incidence of side effects. “Before a drug ever gets to market it undergoes toxicology testing and clinical trials to establish that it is effective but not dangerous,” says science journalist Rachel Ehrenberg. “These trials are often extensive enough to prove that the drug works, but not big enough to say anything meaningful about side effects.” As a result, “many side effects aren’t discovered until after the drug is on the market.” (Ehrenberg, 2012) This problem is aggravated by the fact that an increasing number of new drugs are given an accelerated” review by the FDA, which means they hit the market with less evidence backing them. (Angell, 2005)

There’s also no guarantee about the quality of these studies. For example, of the studies actually submitted to the FDA on antidepressants, 40% had never been published, meaning they never endured any type of even rudimentary peer review. (Begley, 2-8-2010)

Another important caveat to note is that companies usually patent their drugs before starting clinical trials, because they don’t want anyone else swooping in and stealing their potential wonder drug. But this means that clinical trial time eats into a drug’s 20 year patent life. As a result, drug companies are in a rush to speed through the clinical trial phase and get their drugs to market, since each year spent in clinical trials can equate to the loss of billions of dollars in revenue. This rushed approach may further contribute to shoddy research, and it all but assures that drugs will enter the market before any long-term side effects can be discovered.

So-called priority status drug testing, which allow companies an abbreviated and expedited drug approval process, can worsen these issues. In 2017, the anti-dengue vaccine Dengvaxia was approved on a fast-track process. After being administered to thousands of children, it was found that it could WORSEN a dengue-fever infection in those who had never had the infection before, and was only effective for kids who had previously had the illness. (There are different strains of dengue, so a person can be infected up to four times.) It’s just one example of how surprises often turn up AFTER a drug is approved. (Watts, 12-5-2017)

Phase 4: Studies

Even after a drug has been approved and is on the market, companies will conduct what are called phase 4 studies. Sometimes this involves research that the FDA stipulated a company do because there were unanswered questions about safety or efficacy. This is routine whenever a drug is given accelerated approval. But most of the time these are undertaken by the drug manufacturer in order to find new uses for their drug. For example, they might conduct studies to see if they can get an antidepressant to show any benefit in schizophrenic patients or insomniacs. The more uses they can get their drug approved for, the more money they’ll make. If they can win FDA approval for a new use, not only does it expand the market but the company can get an additional 3 years of exclusive marketing rights for that use.

Phase 4 studies are also frequently veiled marketing efforts. Rather than the typical scientific studies, a company might pay a doctor a fee to administer a particular drug and then report back information in the form of a short survey or questionnaire. They know that the fee paid to the doctor (anywhere from a few hundred to several thousand dollars) will be more than recouped by the fact that all his patients are steered towards their drug. In many ways, such loosely defined phase 4 studies are little more than a form of legalized bribery; doctors are being paid to prescribe a particular drug.

Help Us Help Others: