[Reblog] JAMA papers raise questions about FDA drug and device approval

JAMA papers raise questions about FDA drug and device approval.

JAN24 2014

Posted by Gary Schwitzer in FDA

An important series of papers was published in the Journal of the American Medical Association this week.

“Clinical Trial Evidence Supporting FDA Approval of Novel Therapeutic Agents, 2005-2012,” by Dr. Joseph Ross and colleagues, concluded that the quality of clinical trial evidence used by the FDA as the basis of approving new drugs varies widely.  A couple of interesting data points:

• in the seven-year period of analysis, 37% of drugs were approved on the basis of a single pivotal trial.
• trials using surrogate end points as their primary outcome formed the exclusive basis of approval for 45% of drugs approved. (See our primer, “Surrogate markers may not tell the whole story.”)

In an opinion piece,  “Opening the FDA Black Box,” Drs. Steven Goodman and Rita Redberg said the study:

“…raises a host of questions needing further exploration. Despite the FDA requirement for evidence from a minimum of 2 randomized clinical trials supporting an effect on health outcomes, 37% of product approvals were based on only 1 trial, 53% of cancer trials were nonrandomized, and an active comparator was used in only 27% of non–infectious disease trials. Surrogate end points were used in almost all approvals via the accelerated approval process and in 44% of nonaccelerated approvals. Trials were comparatively short, with most lasting less than 6 months, even those assessing chronic treatments for chronic diseases. Cancer drugs, perhaps predictably, were more often approved via the accelerated process and with weaker designs.”

Another paper looked at the reasons that FDA marketing approval for new drugs was delayed or denied.

And a fourth paper looked at FDA regulation of medical devices, “a process that has received relatively little attention,” according to Goodman and Redberg, who continued:

In USA Today, Liz Szabo wrote a good summary of the JAMA papers under the headline, “Not all FDA-approved drugs get same level of testing: Evidence behind FDA-approved drugs and devices often has major limitations.”

Read the entire article here

Related Resources

• ClinicalTrials.gov

ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human             participants conducted around the world.
When available, study results information is included in the study record under the Study Results tab. See How to Find Results of Studies for more information on finding results entered in the results database.

Results (after 2008, only those required by US federal requirements) include
–Participant data (how many started the trial, dropped out, etc)
—  Information about participants (age, gender, blood pressure readings, etc)

[Speaking of gender…]

Good to know, most drugs can affect women and men differently

    —   Outcome (results of taking the drug plus any placebo), with statistics

    –Adverse effects , serious and other (this was not required before 2008)

• Evaluating Health Information (from my personal Google site)

  • Research Articles Summarized for Us All

  • How to Read a Research Paper

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The Cause of the Productivity Crisis in Pharmaceutical R&D; the CBCD Draws Conclusions from a Recent Example

Excerpt from the 15 October 2013 report

The Cause of the Productivity Crisis in Pharmaceutical R&D; the CBCD Draws Conclusions from a Recent Example (PRWeb)

“The pharmaceutical industry is experiencing a productivity crisis in R&D. What is this crisis? First, every year, the pharmaceutical industry is introducing fewer new drugs. Second, a portion of the FDA approved drugs are withdrawn from the market. Third, an analysis of Drugs.com shows that all other FDA approved drugs have many side effects.

What is the source of the productivity crisis?

A compelling explanation is offered in a paper published on March, 2012 in the medical journal Nature Reviews. The paper said that “Much of the pharmaceutical industry’s R&D is now based on the idea that high-affinity binding to a single biological target linked to a disease will lead to medical benefit in humans. Indeed, drug-like small molecules tend to bind promiscuously, and this sometimes turns out to have an important role in their efficacy as well as their so-called off-target effects. Targets are parts of complex networks leading to unpredictable effects, and biological systems show a high degree of redundancy, which could blunt the effects of highly targeted drugs (2).”

In simple terms, the idea that a drug binds with only one target is wishful thinking. As it turns out, every drug binds with many targets in the body, the desired one, and many others. Binding to the ‘other’ targets usually causes all the unwanted, surprising, side effects. [my emphasis]

“The CBCD believes that the current understanding of biology is limited and therefore, the Single Target paradigm is bound to fail.” – Greg Bennett, CBCD” “