Is Big Pharma Hiding Data?

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Over the last few decades, the pharmaceutical industry has produced an astounding number of medicines and treatments that have extended life and improved quality of life. It's also perpetually a target of criticism for everything from profiteering to allegedly concealing damaging information about the safety or efficacy of new medicines. The industry is certainly not perfect and has made its share of mistakes. But far too often, its critics ignore the scientific and regulatory challenges facing the industry.

Ben Goldacre's op-ed in the New York Times ("Health Care's Trick Coin", Feb. 1) is a case in point. It accuses the pharmaceutical industry of burying data that would expose its products as expensive frauds. "In reality," Goldacre writes, "the entire evidence base for medicine has been undermined by a casual lack of transparency."

Goldacre thoroughly misrepresents the real-world challenges of drug research. While the industry, like any industry, has its share of bad actors, the flaws in the clinical-trials system result from a labyrinth of regulatory standards and an abysmally high failure rate in drug discovery--not a conspiracy of evildoers.

It's true that the vast majority of failed clinical trials are not published--because it would be both impossible and impractical to do so. And since drugs fail so often for mundane reasons, little would be added to the medical body of knowledge by writing essentially useless papers.

Still, one can find an enormous amount of data available on clinical trials on the website ClinicalTrials.gov - nearly 140,000 studies have been registered to date from all 50 states and 182 countries, as noted in the chart below. 

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Current trial registration protocols aren't perfect, and Goldacre is right that there's a bias among academic journals to publish positive data from successful clinical trials. But so what? Good news (rare in the drug development world) attracts much more scientific attention than failure (which is the norm). This is human nature, not a conspiracy.

The reality is that most drug candidates fail, at enormous cost. U.S. pharma companies spend close to $60 billion annually on drug development but launch only about 30 or so new medicines (and that's in a very good year). It takes between 5,000 to 10,000 novel compounds during the discovery process to produce just one FDA-approved drug.

And if that weren't daunting enough, eight out of ten successful new medicines won't even generate enough income to make a profit, let alone cover the cost of all the failures. This is hardly the picture of an industry pawning expensive or dangerous placebos off on gullible regulators and doctors.

Goldacre also conveniently ignores that all clinical trials data, good or bad, are disclosed to regulators - the U.S. Food and Drug Administration (FDA) in the U.S. and the European Medicines Agency (EMA) in Europe. Regulators carefully review these data (often hundreds of thousands of pages) and then decide whether the risks of a drug outweigh its benefits - a difficult, expensive, and judgment-laden process that contributes enormously to the cost and time required to bring new medicines to patients.

Furthermore, he implies that trials aren't registered because the industry buries the evidence of a product's ineffectiveness or risk. While this may happen in some cases, it is very rare, and such behavior should be punished harshly. In fact, most of the data from failed trials follows the rule of "garbage in, garbage out"--not even worth paying attention to.

A medicine's failure to produce statistically significant results (e.g., "failure") in a clinical trial can be attributed to several factors: selecting the wrong dosage or dosing schedule, choosing the wrong primary endpoint, or choosing the wrong indication or patient population, to name just a few. A second trial, marginally different from the first, might prove successful simply by making minor adjustments in these parameters. But it doesn't mean that we'd learn any useful (let alone damning) information by publishing the data from the first abandoned effort.

This nuance is lost on Goldacre, who believes that companies simply cherry-pick the data they need to get their drugs approved while burying failed trials. How then to explain extensive media coverage of spectacular failures, such as Pfizer's torcetrapib for increasing "good" cholesterol, or multiple Alzheimer's candidates?

Is the U.S. market really dominated, as Goldacre suggests, by substandard branded drugs pushed by unscrupulous drugmakers?

The data show precisely the opposite. Following a wave of recent patent expirations of blockbuster drugs, close to 80% of the U.S. market consists of cheap generic medicines. The day after a brand name loses patent coverage, someone will be ready to sell it cheaply, and the brand sales often drop to near zero.

Medicines approved by the FDA in 2012 included the first drug to treat cystic fibrosis based on a specific gene defect (G551D), the first product developed from human cord blood, the first drug to treat advanced basal cell carcinoma, and the first drug to treat a rare bone disease (myelofibrosis), as well as a new diagnostic agent for detecting Alzheimer's plaque in the brain.

Out of the 35 new medicines approved in 2012, over half were green-lighted by the FDA using regulatory mechanisms designed to accelerate the review of the most promising new medicines.

This is hardly the picture of an industry indifferent to good science or to the welfare of people suffering from serious and life-threatening diseases. But rather than call for reform of a clinical trials system that is in many ways outdated, unwieldy, and expensive,

Goldacre demonizes Big Pharma. His attack will score him points within a media already inclined to characterize the industry as a cabal of greedy villains.

But it won't make it any easier to bring better treatments to patients.

Paul Howard, PhD, is a senior fellow and director of the Manhattan Institute's Center for Medical Progress. Josh Bloom, PhD, is the director of Chemical and Pharmaceutical Sciences at the American Council on Science and Health.

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