If There Wasn’t Already A Coffee Lobby

Last week the Food and Drug Administration (FDA) announced that it would examine the trend of food products that included caffeine.  This has already prompted one company to pause production on a caffeinated gum.  The announcement follows action in 2010 to withdraw caffeinated alcoholic beverages from the market.  Part of the rationale behind that effort was that the addition of caffeine masked the usual cues people receive from alcohol consumption.  (So those arguing the latest action marks a new intrusion aren’t paying close attention.)

Currently FDA regulations allow the addition of caffeine to products if it meets safety standards and gets included in the ingredients list.  It has only approved the addition of caffeine to products once – for colas in the 1950s (perhaps because it was a replacement for coca).

James Hamblin and others at The Atlantic has been studying the effects of caffeine and its regulatory history.  It would appear that the FDA is focused in part on caffeine in products that are or could be marketed to children.  Michael Taylor, the FDA deputy commissioner that was interviewed for the announcement, appears to suggest that things like energy drinks and breakfast foods with caffeine are the kinds of things the agency is particularly concerned about.  The FDA hasn’t set a level for children, but it recommends a maximum of 400 milligrams for healthy adults.

While it is possible that the recent announcement would be enough to cut back on the number of caffeinated food products, I suspect the FDA will pursue further study.  Whether that ultimately leads to regulation is uncertain, in part because it would not likely be a blanket prohibition.  While implementation of any kind of caffeine regulation will be problematic, focusing on certain products and a specific audience will require more time to develop.

NIMH Looking To Move Beyond DSM

I’ve been seeing (and Retweeting) items on how the National Institute of Mental Health (NIMH) would not be using the Diagnostic and Statistical Manual of Mental Disorders (DSM) when its fifth edition is officially released in a few weeks.  What NIMH means by this relates to a debate between different approaches to mental illness.  The DSM embodies a symptom-based approach to diagnosing illnesses, and NIMH wants to see an approach based more on understanding the neural, cognitive and genetic components that may contribute to mental illness.

To that end, the Institute will be re-orienting its research away from DSM categories to focus on research domains organized by systems (negative and positive valence systems, cognitive systems, arousal/modulation systems and systems for social processes).  This approach, called Research Domain Criteria, is intended to develop a new classification system that takes advantage of research in genetics and neuroscience to try and find sub-types within broader demonstrated illness groups.  If they can be found (as they have in other diseases), it could mean improved treatments and/or means of prevention.  Research in other diseases has led to this kind of improvement, and it would be lovely if the same possibility could be realized for mental illnesses.

Of course, this approach is still in its infancy, and years of work will be needed before it can effectively contribute a new diagnostic system.

Buying The World A Coke-Reliable Distribution System

While Coca-Cola isn’t the best drink for you from a health perspective, its distribution network is being used for healthier purposes.  The documentary film The Cola Road describes how non-profits are using the Coca-Cola distribution network to make it easier for remote villages to obtain needed rehydration medicines (and no, the tasty beverage doesn’t count) (H/T Scientific American).

Dean Kamen has also turned to Coke for help getting his products to those who could most benefit from it.  In this case, it’s his water purification system, the Slingshot.  He explained the specifics back in 2008 on The Colbert Report.  Last fall he partnered with Coca-Cola (and others) to produce the Slingshots at scale and test the machines in rural health centers in Latin America throughout 2013.  Given Kamen’s past work with Coca-Cola (his company helped develop the Freestyle soda machine) this partnership is not surprising.  Coke is committed to replenishing 100 percent of the water it uses in producing its beverages by 2020, and having purification machines like the Slingshot available should make that goal easier to achieve.

Next time you’re thinking about innovation, hopefully the example of Coca-Cola can remind you that getting the product to market is at least as important as developing it in the first place.  Maybe if Coca-Cola had need for Kamen’s Segway scooter, they’d be a bit more commonplace than they are.

The Government Really Doesn’t Know What To Do About Emergency Contraception

In what appears to be a classic case of agencies not talking to each other, the Food and Drug Administration (FDA) and the Department of Justice are sending mixed messages in response to a recent court decision on the emergency contraception Plan B.

On Tuesday the FDA announced that they have approved a petition to allow the marketing of Plan B One-Step to women 15 years and older without a prescription.  The court order stipulated that emergency contraception should be made available without age restrictions, and is supposed to take effect on May 6.  The FDA apparently is trying to dodge the order in its announcement by stating this is a separate petition from the one subject to the court order.

To complicate matters a bit, the Justice Department has announced it will appeal the court order.  It has filed a petition for a stay of the order pending the appeal.  It’s grounds for appeal relate to what the Department sees as an overreach of the judge’s authority.  There’s a touch of irony here as the judge claimed that the actions of the Secretary of Health and Human Services in this matter were unprecedented, at least implying an overreach of her authority (pages 37 and 39).

Independent of the litigation over access to Plan B without age restrictions, the FDA announcement lowering the age restriction (without a prescription) to 15 will take effect immediately.  Per the announcement:

“The product will now be labeled “not for sale to those under 15 years of age *proof of age required* not for sale where age cannot be verified.” Plan B One-Step will be packaged with a product code prompting a cashier to request and verify the customer’s age. A customer who cannot provide age verification will not be able to purchase the product. In addition, Teva has arranged to have a security tag placed on all product cartons to prevent theft.”

The petition requesting a stay of the court order requested a decision by the end of today, as the order is due to take effect soon.

NCI To Examine Supposedly Failed Clinical Trials

The National Cancer Institute (NCI) is looking for ‘exceptional responders’ to the clinical trials associated with potential cancer drugs.  Such responders would be patients that responded well to drugs that the bulk of the trial population did not.  The hope is that determining why these responders did so well can provide insight into both the drugs and the specific cancers that they were targeting.

Part of this evaluation program ties into recently passed legislation that could allow drug approval for those substances that show evidence of exceptional responders.  The NCI and the Food and Drug Administration will work together on determining the details of the relevant approval tests by the legislative due date in 2014.

Efforts like these, to extract additional scientific knowledge from experiments, may become more common.  Changes in data analysis capacity make it easier to analyze experimental results, and connect them to personalized medical information (like a patient’s genome).  Outside the scientific perspective, funders seem likely to continue a one-two punch of constraining available resources and expecting greater direct return on their investment in research.  Trying to squeeze scientific blood from experimental turnips will become more appealing expeditious.  I prefer to think of it this way – when you’ve learned all you can from an experiment, how can it really be a failed test?

ProPublica Reminds Us That FDA Still Needs Repairs

The recent judicial rebuke over emergency contraception is just the latest example of the challenges the Food and Drug Administration (FDA) has had in getting its scientific and regulatory houses in order.  The kerfuffle over Plan B is different (but not an isolated incident) in that the interference in agency processes came from outside the FDA, rather than from within.  But the agency has a lot of work to do to deal with the conflicts, delays and struggles over drug and device approvals.  The agency is trying (the Commissioner did publicly disagree with the Secretary over Plan B), but it has a long way to go.

This week’s reporting by ProPublica (H/T Scientific American) focuses on the FDA’s relationships with contract drug testing companies.  The reporters recount how two companies were found to have conducted years of tests that were either unreliable or fraudulent.  As a result over 300 drugs needed to be retested, with at least 140 of those drugs already approved for sale.

None of the drugs were pulled from the shelves, even temporarily.  No public statements were made by the FDA about the retesting, even though the European Medicines Agency pulled seven drugs tested by one of the labs.  The FDA remains tight-lipped on the matter, and ProPublica has been able to identify only five drugs that were approved at least in part due to suspect tests of one of the two companies, Cetero (the other company is MDS Pharma Services).

(ProPublica has a number of other investigations worth looking into, many of which focus on medical and/or scientific topics.)

Clearly the FDA still has many challenges to tackle before it can effectively fulfill its regulatory obligations.  The bigger problem, as I see it, is an institutional culture that accepts glacially-paced efforts to correct errors, coupled with a complete lack of interest in informing the public.  I don’t envy Commissioner Hamburg’s task in trying to tame the agency.  I wish her the best of luck.

So Will Someone File A Scientific Integrity Complaint Against Secretary Sebelius?

In late 2011 Health and Human Services Secretary Kathleen Sebelius overruled the judgment of the Commissioner of the Food and Drug Administration (FDA) to prevent the availability of emergency contraception over the counter for girls under 17 without a prescription.  The decision was the culmination of a review ordered by a federal judge in 2009 in part to counter political interference in a scientific review of emergency contraception.  The Secretary attempted to provide scientific justification for her decision, which included concerns that the studies used in the review did not cover all ages that could possibly be provided access if the drugs were made available over-the-counter.  As I noted shortly after the decision, she made her decision a fight over science.  That reflected my lack of knowledge of the ongoing case.

Last week the federal judge that ordered the review issued another order chastising the Department for its decision.  As it did back in 2011, the Obama Administration stands by Secretary Sebelius and her decision.

The judge essentially concluded that the kinds of political interference that prompted the first review – connected to a previous administration – persisted into the current administration.  From page 11 of the Order:

“In my 2009 opinion, I traced the evidence demonstrating that the conduct of the FDA was influenced by the Bush White House, acting through the Office of the Commissioner of the FDA, and I held that this kind of political interference called into serious question the legitimacy of the FDA’s decision. In the present circumstances, the political interference came directly from the Secretary of Health and Human Services, a member of the President’s Cabinet.”

The case that he is dealing with is a Citizen Petition (filed in 2001, with the lawsuit following in 2005) to have the FDA “make all levonorgestrel-based emergency contraception, including Plan B, available for over-the-counter sales without age or point of sale restrictions.”

The judge has ruled that the FDA must make levonorgestrel-based emergency contraception available over-the-counter without a doctor’s prescription or point-of-sale or age restrictions.  The agency has 30 days from the date of the order (April 4) to comply.

Brain and Brain! What Is BRAIN?

Those who get the allusion in the title, the program in question still stinks.

Announced at the beginning of April as one of the Obama Administration’s Grand Challenges, BRAIN (Brain Research through Advancing Innovative Neurotechnologies) is a new multidisciplinary, multi-agency program with roughly $100 million in the President’s recently announced budget for Fiscal Year 2014.  (Must note here the chronic failures of Congress in passing budgets make this funding far from a sure thing.)

Besides the federal research component (roughly $100 million from the National Institutes of Health, the Defense Advanced Research Projects Agency/DARPA, and the National Science Foundation) BRAIN will engage several non-governmental organizations to add over $100 million in additional research support.  The NGOs are the Salk Institute for Biological Sciences, the Kavli Foundation, the Howard Hughes Medical Institute and the Allen Institute for Brain Science.  The funding is anticipated to persist over a ten-year period.  So if the federal budget continues to be dysfunctional, there will still be some engagement in BRAIN.

Advisory Bodies Have BRAIN On Their Minds

Both the President’s Council of Advisers on Science and Technology (PCAST) and the Presidential Commission for the Study of Bioethical Issues will meet in 3 weeks.  Given recent developments, it seems likely they will both have a topic in common.

The Commission is scheduled to meet in Washington on April 30.  No agenda is available as of the day of this posting, but the Federal Register notice for the meeting indicated that incidental findings would be a focus.  Incidental findings have been on the Commission’s agenda for a while.  They represent data found from research and experiments that were beyond the scope of the research.  Typically this is an ethical challenge because informed consent of human subjects involved in such research is typically focused on the designed purposes of the research.

However, at the beginning of this month the President notified the Commission that he will formally request their input on the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) program.  This is a new cross-agency (National Science Foundation, National Institutes of Health, Defense Advanced Research Projects Administration/DARPA) program intended to increase our understanding of how the brain functions; how we think, learn and remember.  The Commission will be asked to evaluate the ethical, legal and societal implications of the program and related developments in neuroscience.  Comparisons to the Human Genome Project have already been made.

Also interested in BRAIN is PCAST.  During the public session (there have always been non-public sessions of PCAST meetings, they just started acknowledging it in print) of its May 3rd meeting (draft agenda), PCAST will hear from the DARPA director and the National Science Foundation Assistant Director for Biological Sciences.  PCAST has held discussions on neuroscience before.  It is possible that PCAST may pursue a report on this topic, but that likely won’t be clear until at least after the upcoming meeting.  The other part of the public session (aside from the usual public comment session) will focus on the impact of technological advances on productivity and employment.

Internet Searching For Side Effects Can Discover Side Effects?

In what might possibly be seen as a self-fulfilling prophecy, researchers have used internet search data to determine side effects for drugs not otherwise known when the drugs were initially developed.  Such a search would be independent of the reporting mechanism the Food and Drug Administration (FDA) uses to identify side effects post-testing.  The specific focus of the study ($), which was a collaboration between researchers at Stanford, Microsoft and Columbia, looked at search queries to determine possible side effects of combinations of drugs.  This follows on similar work looking through the FDA’s Adverse Event Reporting System for drug-drug side effects.  The study indicated side effects could be found in an automated way, which is a bit more thorough and perhaps reliable that the FDA system, which is voluntary and relies on physician input, rather than feedback directly from the patients.

The parallel here is Google Flu Trends.  However, search engine data as a predictor of health concerns is inexact.  Google Flu Trends did a horrible job estimating this year’s outbreak, possibly because news coverage of flu in January skewed the analysis of subsequent search data.

It certainly is possible that some of the side effects found via search data will not present themselves at the anticipated rate due to searches prompted by reasons other than the searcher experiencing them directly.  But since this work is focused on drug-drug interactions, it’s possible that the smaller affected populations (those using both drugs) may control for the kind of discrepancy Google Flu Trends found this year.    More analysis needs to be done, and I think it fair to say that the FDA (or in the case of Google Flu Trends, the Centers for Disease Control) shouldn’t forego their own reporting systems in favor of mining online search data.  Having an additional tool is great, but there’s not yet a reason to throw out what’s worked in favor of what might be faster, if not as reliable.