The Drug Approval Process in the US (and Off-Label Uses)

      The Federal Drug Administration (FDA) is responsible for approving medicinal drugs for use within the US, based on perceived safety and efficacy.  Before the FDA will approve a drug, it must go through an extensive research process that involves first testing various compounds on tissues and animals to find promising candidates, then testing the promising drugs on human through a series of trials, each one involving a larger number of people.  Phase I trials aims to determine safe doses. Phase II trials look like the final experiments in animals, having control and experimental groups to determine if the drug has benefits over no treatment or previously used treatments.  Phase III trials are on a larger scale to confirm that all relevant populations respond as determined in Phase II.  An unsuccessful trial at any stage results in cancellation of the process, and successful human trials often last up to 6 years.  Once the drug makes it through Phase III trials it can be patented and made available to the public.  The company that discovered and tested the drug usually maintains exclusive access to marketing the drug for 20 years from the start of trials, after which point other companies can make generic versions that undergo a much shorter testing process. 

      The process is very rigorous, and thus the advantage of the process is that citizens can feel relatively confident that the medical treatments they’re receiving are safe and effective.  However, it also means that the US is slower than many other countries at making some treatments available to its citizens.  As a result, some individuals will seek treatment in other countries with much more flexible rules, all at their own risk.   A related short-cut to access is using drugs for a medical condition other than the one that the clinical trials investigated.  This practice is called “off-label” use.  Although the safety of the drugs has been tested on one type of population, safety is not necessarily guaranteed for another patient population.  Efficacy has also not been fully vetted.  Doctors should make clear to patients when the drugs they’re prescribing are being used off-label, but patients may not always recognize what this term means or the risks and benefits associated with such use. - SLB

Source read before class:

Botox: The drug that is treating everything.  By Alexandra Sifferlin in TIME Magazine.  2017.  

Recommended sources for further engagement:

The $2.5-billion mistake:  A gullibleTrump bought into Big Pharma’s inflated claim about drug R&D costs.  By Michael Hiltzik in the Los Angeles Times.  2017.  – An opinion piece about costs of the approval process and potential plans to alter the approval process 

Testing drugs on the developing world.  By Stephanie Kelly in The Atlantic.  2013. – One way to make drug testing cheaper is to outsource testing to other countries.  This article summarizes the process and potential issues.  

Overview of clinical trials.  At Centerwatch.com. - A bit more about what happens at each stage and how many drugs make it through

Popular books or movies that address the topic:

The Constant Gardener (2005) – fictional thriller about overseas drug trials in Africa; based on a novel of the same name by John Le Carré.  

The Scientific Process and Its Problematic Incentives

When you learn about the scientific process in school science courses, it usually begins with an hypothesis and ends with conclusions or creation of a new hypothesis.  However, there are many other logistics involved with the scientific process, including receiving funding and publishing your findings.  The pressures associated with funding and publishing can lead to questionable research practices (QRPs) and outright fraud by scientists desperate to maintain the right to keep doing science.  Money is necessary for most experiments, and frequently publishing results is often required for receiving grants (and keeping one’s job).  Scientists may plagiarize, selectively choose data to include, and take shortcuts on ethical treatment human or animal subjects, among other things.  Although some of these QRPs are committed with the intent to mislead, others are likely done in good faith, with the researchers just looking to speed up the sharing of exciting findings they “know” to be true.  Whatever the reason, QRPs have the potential to promote misinformation, resulting in 1) the media sharing reactive, but untrue and thus dangerous information with the public, and 2) other scientists wasting time trying to replicate or build upon findings that don’t stand the test of time

The above suggests that researchers are to blame for a lot of the misinformation.  However, the system itself is also problematic, as we prioritize publication of novel, unexpected results.  Science is supposed to be “self-correcting”, in that once we find out that an earlier experiment’s data doesn’t hold up we publish new information, but when only the first study receives publication in prestigious journals or media attention, misinformation lingers much longer than it should.  Some of these cases are now well known (like the [non]link between vaccines and autism), but recent studies suggest that a large percentage of studies, across multiple disciplines, are not replicable, at least in terms of finding statistical significance. - SLB

Source read before class:

Communicating neuroscience: hype and the sources of spin.  By Timothy Caulifield as part of the Brains Matter!  Vancouver. Brain Science and Social Responsibility. Thematic Sessions Video Podcasts.  2014.  

Recommended sources for further engagement:

Falsepositives: fraud and misconduct are threatening scientific research. by Alok Jha in the Guardian. 2012. - A review of reasons scientists cheat and some of the dangers of doing so.

How many scientists fabricate and falsify research? Asystematic review and meta-Analysis of Survey Data.  Daniele Fanelli in PLOS One.  2009. - A peer reviewed article that highlighted just how common problems may be in science. (A bit dense, but nice to see the methods and data so you can draw your own conclusions)

Study that undercut psych research got it wrong. Peter Reuell in the Harvard Gazette.  2016.  - There was a study that made the news last year stating that most psychology studies weren’t replicable.  This article explains some of those findings and some of those critiques.  (The article itself is available through Science if you have access.)

Reproducibility in cancer biology: Makingsense of replications.  Brian Nosek and Timothy M Errington in eLife.  2017. - Since the psychology non-replication study was published, the same group has been trying to replicate other fields.  Here is the most recent, demonstrating that cancer research isn’t replicable either.