Stacking the Deck with Clinical Trials

© photosebia |

© photosebia |

In September of 2007 the “Food and Drug Administration Amendments Act of 2007” became law. This law requires that findings from human testing of drugs and medical devices be made publically available on the NIH website, But it seems that both drug companies and most research institutions—including leading universities and hospitals—routinely violate the law. An investigation by STAT News found that at least 95 percent of all disclosed research results were posted late or not at all.

Drug companies have long been castigated by lawmakers and advocacy groups for a lack of openness on research, and the investigation shows just how far individual firms have gone to skirt the disclosure law. But while the industry generally performed poorly, major medical schools, teaching hospitals, and nonprofit groups did worse overall — many of them far worse.

Four of the top ten recipients of federal medical research funding from the NIH were among the worst offenders. These four were: Stanford, the University of California, San Diego, the University of Pennsylvania, and the University of Pittsburgh. Researchers, university administrators and hospital executives interviewed by STAT News said they were not intentionally breaking the law. They were just too busy and lacked administrative funding to complete the required data entry on NIH estimated it takes, on average, around 40 hours to submit trials results.

Six organizations — Memorial Sloan Kettering, the University of Kansas, JDRF (formerly the Juvenile Diabetes Research Foundation), the University of Pittsburgh, the University of Cincinnati, and New York University — broke the law on 100 percent of their studies — reporting results late or not at all.

The Director of NIH, Francis Collins, said the findings were “very troubling.” He said pointing to the time demands on posting data to was not an acceptable excuse for noncompliance. Beginning in the spring of 2016, after further refinement of the rules, Collins said NIH and FDA will have “a firmer basis for taking enforcement actions.” The FDA is empowered to levy fines of up to $10,000 a day per trial for late reporting to

In theory, it could have collected $25 billion from drug companies since 2008 — enough to underwrite the agency’s annual budget five times over. But neither FDA nor NIH, the biggest single source of medical research funds in the United States, has ever penalized an institution or researcher for failing to post data.

When the “Food and Drug Administration Amendments Act of 2007” became law, Senator Charles Grassley said: “Mandatory posting of clinical trial information would help prevent companies from withholding clinically important information about their products. . . . To do less would deny the American people safer drugs when they reach into their medicine cabinets.” But the failure of drug companies and others to post clinical trial results, coupled with the failure of the FDA to hold them accountable via fines when they don’t, means the American people are being denied the ability to see for themselves if the drugs they take are safe and effective. Kathy Hudson, a deputy director for NIH, said:  “If no one ever knows about the knowledge gained from a study, then we have not been true to our word.”

The scarcity of clinical trial results posted to is not the only issue with clinical trials and the NIH website. Drug companies and research facilities are also not prospectively registering clinical trials as they should. Scott, Rucklidge and Mulder found that “less than 15% of psychiatry trials were prospectively registered with no changes in POMs [primary outcome measures].” You can see Julia Rucklidge’s discussion of the study here. Also see “Clinical Trial Sleight-of-Hand” on this website.

Writing for Health Care Renewal, Bernard Carroll said there was a disconnection between the FDA’s drug approval process and what gets published in the medical journals. “Pharmaceutical corporations exploit this gap through adulterated, self-serving analyses, and the FDA sits on its hands.” He suggested that independent analyses of clinical trials be instituted, “because we cannot trust the corporate analyses.”

When corporations are involved, there is no point in prolonging the myth of noble and dispassionate clinical scientists searching for truth in clinical trials. It’s over. We would do better to stop pretending that corporate articles in medical journals are anything but marketing messages disguised with the fig leafs of co-opted academic authors and of so-called peer review.

Carroll proposed that Congress mandate the FDA to analyze all clinical trials data strictly according to the registered protocols and analysis plans. This should apply to new drugs as well as approved drugs being tested for new indications. And it should be applied to publications reporting new trials of approved drugs. “Corporations and investigators should be prohibited from publishing their own in-house statistical analyses unless verified by FDA oversight.” (emphasis in the original) Carroll quoted Eric Topol in a recent BMJ editorial as saying: “The disparity between what appears in peer reviewed journals and what has been filed with regulatory agencies is long standing and unacceptable.”

He gave three reasons for prohibiting in-house corporate analyses of clinical trials data. First, the inherent conflict of interest is too great to be ignored. Carroll described Forest Laboratories and citalopram as an example in his article to illustrate this point. Second, when corporate statisticians are encouraged to play around with the statistical analysis of the trial data (i.e., p-hacking), “they are no longer testing the defined study question with fidelity to the methods specified in the IND protocol.” Third, the FDA should monitor the publication of clinical trial reports in medical journals. The FDA inspects production facilities for evidence of physical adulteration, why not verify that what gets published in journals matches what they presented to the FDA for drug approval? “The harms of adulterated analyses can be just as serious as the harms of adulterated products.”

Pharmaceutical corporations are betting on huge profits with drug development. And allowing them to play fast and loose with clinical trial registration and the analysis of the trial data is akin to stacking the deck in their favor. It’s time to require pharmaceutical companies to stop trying to rig the clinical trial process in their favor.

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