Category: FDA

Unreliable Biomedical Science, and a Solution?

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By Christopher Robertson

The Economist has a long, detailed, and readable piece about the difficulties of inferring anything from the published findings of biomedical science.  There are all sorts of problems that fall short of scientific fraud, including the the biases caused by industry-funding of biomedical science, the biases of unblinded raters who see what they want to see, and the biases of journal editors towards only publishing “positive” findings.  (I am particularly enamored with this graphic, which shows the fundamental problem of inference.)  It is rare for researchers to even bother to attempt to replicate prior findings, but when replications are attempted, they often fail.  

The Economist piece can be read as something close to an outright assault on empiricism, at least as we now know it.  In practical terms, it is prudent for physicians, patients, and payors to be wary of the findings presented in even the top journals.

One of the beauties of our scientific system is that it is wildly decentralized.  Scientists (and their funders) can test any hypothesis that they find interesting, and they can use whatever methods they prefer.  Likewise, journal editors can publish whatever they want.  While such academic and market freedom is attractive, it results in quite a hodgepodge of science, with replication studies and publication of null results being afterthoughts.  The NIH and NSF have in the past functioned to set an agenda and demand rigor, but as their funding wanes, the chaos waxes.

The problems are scientific, but any solution will be institutional (and thus legal).  I have argued for a partial solution to industry bias in my short article, called “The Money Blind:  How to Stop Industry Influence in Biomedical Science Without Violating the First Amendment.”  Independent scientific testing could be conducted by a neutral intermediary, which would pool funds.  In a similar vein, there is also a new project of the Science Exchange, called “The Reproducibility Initiative.”  This program offers to be the independent scientific agency, which attempts to validate known results.   But there is not yet a large-scale funding model in place.  If biomedical journal editors would at least put disclosures in their structured abstracts (an intervention we have tested), over the long run that may also nudge industry to use such gold-standard independent testing, when they have something that is truly provable.  And, at least in the domain of the products regulated by the FDA, the agency should consider using its current statutory authority to push companies towards independent, robust, and replicated science.

Popular Distrust of Health Science: A Crowdsourced Solution

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Benjamin Waterhouse's GraveBy Christopher Robertson

Enjoying the fall foliage in Mt. Auburn Cemetery yesterday, I came across this marker for Benjamin Waterhouse.  In the overwrought language that is appropriate on a grave marker:  “In 1800 he introduced to the new world the blessing of vaccination.  Overcame popular prejudice and distrust by testing it on his own children and thus established a title to the gratitude of future generations.”

No less today, there seems to be plenty of popular distrust of elite science.  (And it doesn’t help that so much of contemporary science is infected by conflicts of interest.)  Self-experimentation does have a long venerable history, which has recently become more prominent in the quantified self movement.  (I’m not sure about experimenting on my kid though.)

Tomorrow, I’m heading to NYC to make a pitch to the Robert Wood Johnson Foundation’s Pioneer Fund, for major funding to launch a new project that would create a platform for robust, randomized experiments of lifestyle interventions (think: migraine management, diets, exercise regimens, nutritional supplements) for which there is virtually no FDA oversight and thus no regulatory imperative for rigorous scientific investigations.  Nonetheless, these lifestyle factors are the primary drivers of health and healthcare costs.  By crowdsourcing these sorts of experiments in an sound ethical framework robust against institutional corruption, I hope to develop gold-standard scientific knowledge with huge samples, but also build public engagement, public understanding, and public trust of health science.

The crowd uses Wikipedia to organize knowledge, and Indiegogo to invest in new health devices.  The crowd needs a platform to create knowledge too, especially through randomized interventions, which have the potential to actually change behaviors for the better and eliminate the confounding factors that undermine observational studies.

So, wish me luck in NYC tomorrow:   https://bit.ly/pioneerpitch

Taking China’s Food Safety Problem Seriously (II)

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By Ching-Fu Lin

[See Part I here.]

In response to the melamine-tainted milk scandal in 2008, China replaced its outdated Food Hygiene Act with the Food Safety Law, which came into effect in 2009.  The 2009 Food Safety Law includes provisions on risk assessment methods, establishment of a food safety committee, mandatory product recall requirements, and unification of food safety standards.  However, this legal reform has left many key areas of the regulatory framework intact—such as industry compliance and law enforcement.

First, the crucial problem of overlapping competencies among responsible authorities is not addressed in the 2009 Food Safety Law.  Although the Ministry of Health (MOH) is mandated to take the lead on food safety regulation, the current state is flawed as multiple agencies are only organized in a loosely coordinated system.  For example, the State Food and Drug Administration (SFDA), the Ministry of Agriculture (MOA), the State General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ), and the Ministry of Commerce (MOC) all take part in the regulation of the entire food supply chain.  The result is a fragmented regulatory environment, which creates blind areas for agencies to push responsibility away, and therefore, perpetuate rather than alleviate loopholes in routine control.  Thus, timely response and cooperation is difficult.

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Taking China’s Food Safety Problem Seriously (I)

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By Ching-Fu Lin

Why should we be concerned about China’s food safety problem?  A recent opinion by Adam Minter on Bloomberg offers yet another tough criticism on China’s food system: “For more than a decade, China has earned a reputation as one of the world’s worst food-safety offenders.”  Melamine-tainted milk, rat meat sold as lamb, recycled “gutter oil” for cooking, and most recently, juice made from rotten fruit, Chinese food producers never cease to surprise us with their “creativity” in economic adulteration.  The Chinese government, however, has failed to establish an effective regulatory system beyond executing violators and political campaigns.  The Chinese consumers continue to react with desperation to these endless food safety crises, smuggling bunks of infant formula from Hong Kong and other countries.

But why should we care?

According to testimony before a subcommittee of the House Foreign Affairs Committee in May, food products of Chinese origin have dominated the U.S. food market in areas such as tilapia (77.5%), apple juice (65.2%), cod (52.7%), processed mushrooms (34.1%), garlic (27.4%), clams (16.1%), frozen spinach (16.0%), and salmon (12.7%).  The Chinese food imports are also expected to increase by about 10% annually until 2020.  Faced with the huge volumes of foods imported into the US every year, the Food and Drug Administration has only been able to inspect about 2.3% of the total imports from China in 2011 (which is, well, an improvement compared to 1.3% in 2007). Moreover, the U.S. Department of Agriculture announced last month that China’s poultry processing inspection system is equivalent to its US counterpart.  That is, processed chicken from China is determined as meeting US food safety standards (even if there are no on-site USDA inspectors in the processing facilities) and granted it access to the US market.

In an interdependent world trading system, regulatory failure in one country can spill over to many others, resulting in adverse public health repercussions in the latter country.  We should take China’s food safety problem seriously.

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Foodborne illness and the government shutdown

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By Nicholson Price

This story is still developing, so this post will just be a quick pointer.  You may have seen news stories about how FDA isn’t inspecting foods, and 90% of seafood isn’t getting inspected.  And these are all worries about problems that we think might happen.

Well, the problems have started.  Salmonella-contaminated chicken has sickened 278 people across 18 states.  The USDA’s Food Safety and Inspection Service (FSIS) is still operating as an excepted activity (pdf link, see page 2), and has announced the outbreak but the CDC may be unable to do interstate surveillance of the outbreak (exactly what CDC is able to do during the shutdown is a bit unclear).  And FSIS only covers meat, poultry, and eggs.  FDA, which inspects most other foods, won’t be doing so as long as the government is shut down.

And for folks who happen to go to the USDA site looking for answers (as opposed to linking right to the FSIS), they’ll get this message: “Due to the lapse in federal government funding, this website is not available.”

Praise for Price’s “Making Do in Making Drugs”

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Check out this nice write up of PFC Academic Fellow Nicholson Price‘s paper, Making Do in Making Drugs: Innovation Policy and Pharmaceutical Manufacturing, over at the Written Description IP blog.  Says blogger , “Price’s paper leads to a host of new and interesting questions, and his thorough research revealing potential shortcomings of the FDA approval process is likely to be very useful . . . .”

Government Regulation of the Practice of Medicine: How the FDA overreaches the regulation of medical practice

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By Richard Epstein

A sound scheme of public regulation seeks to find the best way to align the incentives of public regulators with the interests of the public at large.  That task has proven to be particularly acute with the U.S. Food and Drug Administration, which possesses vast powers to regulate the manufacture and distribution of drugs and medical devices in the United States, which it all too often overuses.

In a recent study for the Manhattan Institute entitled The FDA’s Misguided Regulation of Stem-Cell Procedures: How Administrative Overreach Blocks Medical Innovation, I examine the FDA’s over-regulation of new stem-cell technology in connection with the 2012 decision of Judge Rosemary Collyer (District Court of the District of Columbia) in Regenerative Sciences LLC v. United States.

That case examined the line between the regulation of pharmaceutical products on the one hand and the practice of medicine on the other. It is well established that the FDA has power over the former, but lacks power over the latter.  That distinction is of no small consequence because it allows, for example, for the rise of an extensive market in “off-label use” by physicians of drugs for purposes for which they have not received FDA approval.  This class of drug use is very large, and in cancer cases is thought to be more common than treatment using FDA-approved products.

The persistence of off-label drug use should caution people about allowing the FDA to exert extensive control over the drug licensing process.  It could be that the thousands of physicians, hospitals, and patients that use drugs off-label have, time after time, all made some major mistake.  Or it could just be possible that the accumulated level of institutional knowledge post-release demonstrates that the FDA has been too restrictive in its decisions as to whether a new drug should be allowed into the marketplace in the first instance. The FDA is heavily incentivized to be tough in its approval process lest it take heavy criticism for the all-too-visible injuries that may be caused by approved drugs. But in the social calculus, the individual losses that occur to people who are denied treatment by the heavy-handed actions of the FDA count every bit as much.  Yet these diffuse losses, often undocumented, bring much less heat to the FDA, which accordingly is prepared to shrug them off as a cost of supplying people the “protection” that is so central to the FDA mandate.

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“When Truth Cannot Be Presumed” Burning Up SSRN

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Make sure to check out “When Truth Cannot Be Presumed: The Regulation of Drug Promotion Under an Expanding First Amendment,” by our very own blogger – and former Petrie-Flom Center Academic Fellow – Christopher Robertson.  Chris presented this paper at our annual conference last year, blogged about it here, and must really be on to something, as his paper has already been downloaded from SSRN more than 1,100 times in the past 10 days.  Take a look for yourself.