FDA Doings: Always in the Crosshairs

Doc Gumshoe looks at the drug and device approval process

By Michael Jorrin, "Doc Gumshoe", February 19, 2014

[Ed note: Following is another installment from our favorite medical scribe, “Doc Gumshoe” (no, he’s not a doctor). We feature Michael’s commentary every couple weeks or so, and his thoughts and words are his own. “Doc” doesn’t pick stocks, but FDA decisions are a huge driver of investment success for pharmaceutical and biotech companies and today Michael does some explaining about how the FDA and clinical trials work.]

Readers of this blog have a pretty wide range of opinions about the FDA, although the more outspoken of you mostly chime in with negative comments. Doc Gumshoe, being aware of the many stark conflicts between the FDA and drug companies, is a skeptic regarding the view that the FDA is in cahoots with Big Pharma. But this little piece looks at a few areas where the FDA’s recent practices have been subject to criticism from elevated sources. Before I go on to cite chapter and verse, I should recap some of the specific hurdles that the drug and device approval process has to leap over.

What does a treatment have to demonstrate to gain FDA approval?

The answer, in two words (plus a conjunction) is efficacy and safety. That goes for any intervention, whether it’s a drug or a device or any other kind of treatment. But how can that be demonstrated? If we’re talking about a drug, the gold standard is the randomized, placebo-controlled clinical trial, in which the candidate drug demonstrates at least some advantage over an existing drug. The advantage could be with regard to any of several parameters – a greater percentage of patients attaining a specific marker, a more rapid onset of action or a longer duration of action, a lower incidence of adverse effects, and a number of others. And this advantage needs to be statistically significant, meaning that the results of the clinical trial must be highly unlikely to have been a matter of chance.

There are lots of obstacles that the pharma company has to overcome. Here are just a few:

If there are already some fairly effective existing drugs for a disease, it’s likely to be difficult to enroll patients in a trial where the patient would not know whether he/she was going to get the existing drug, or a placebo, or a new experimental drug.

If the trial calls for patients/subjects who have never taken a drug for that disease or condition – drug-naïve patients, as they are known – it may be exceedingly difficult to recruit enough patients for the kind of big Phase 3 trials the FDA likes to see. Patients newly diagnosed with a disease or disorder want to be treated with a drug that is known to work.

Then there’s the issue of diseases/disorders/conditions that don’t affect large numbers of people. Again, in such cases, it may be difficult or impossible for drug companies to enroll enough patients for multiple clinical trials.

For those reasons (and others) lots of trials are now being conducted in the so-called “less developed” parts of the world, and sometimes, perhaps, with less rigorous standards than would be expected.

… and, of course, there’s another issue …

Namely, how long it takes for some drugs to get approved and available for treatment. We all remember the early days of the AIDS epidemic. When there was something like a promising drug coming along, there was intense pressure to get that drug to people who were dying of AIDS. That got a lot of publicity, and the FDA got it in the neck for being “obstructionist” – that is, for insisting on going through the time-consuming approval process.

The FDA, to some degree, initiated changes in their procedures – mostly a matter of streamlining the bureaucracy and simplifying procedures.

But in response to the clear need to speed things along – get drugs to the patients who need them – the FDA has also instituted some changes in the requirements for approval, specifically for some medical conditions, based on such issues as limited availability of treatment options and urgency of getting some kind of treatment to patients who might have rapidly deteriorating illnesses.

“Breakthrough Therapy Designation,” or BTD

Here’s a statement directly from the FDA:

Fact Sheet: Breakthrough Therapies

On July 9, 2012 the Food and Drug Administration Safety and Innovation Act (FDASIA) was signed. FDASIA Section 902 provides for a new designation – Breakthrough Therapy Designation. A breakthrough therapy is a drug:

  • intended alone or in combination with one or more other drugs to treat a serious or life threatening disease or condition and
  • preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

If a drug is designated as breakthrough therapy, FDA will expedite the development and review of such drug. All requests for breakthrough therapy designation will be reviewed within 60 days of receipt, and FDA will either grant or deny the request.

Please refer to section 902 of FDASIA for more specific information about this provision. Additionally, a draft Guidance for Industry: Expedited Programs for Serious Conditions––Drugs and Biologics was published on June 25, 2013, and includes information such as qualifying criteria for breakthrough therapy designation, features of the breakthrough therapy program, and guidelines on how to submit a breakthrough therapy designation request.

As of the beginning of 2014, the FDA had received over 100 breakthrough therapy designation (BTD) requests and approved only about 30%. They declined about 60% and another 10% or so are curr