speaking of about time!…

Posted on Wednesday 19 November 2014

I know I said that I was taking something of a sabbatical to finish up a project, but I broke that to post the Newsweek article last week [see about time…]. And I’m doing it again because this just came my way – and it’s huge!:
The Chronicle of Higher Education
By Paul Basken
November 19, 2014
[behind pay-wall]

The Obama administration on Wednesday proposed new rules aimed at forcing researchers to publicly post details of medical trials involving human subjects, saying compliance to date has been woefully insufficient. For years, the government has required researchers using federal money, or seeking federal approval for a medical intervention, to announce the details of their trials in advance and post the results. But that hasn’t happened often enough, National Institutes of Health officials said. As evidence, they cited a study conducted at Yale University in 2012. Researchers studied a sample of trials using NIH money and found that fewer than half had results published within 30 months of the trials’ end.
    "We as a community have a disappointing track record" of disseminating trial results, said Francis S. Collins, director of the NIH, in a briefing outlining the proposed new rules.
Registering trials in advance and reporting the results afterward are critical to ensuring the integrity of studies, protecting patients, and building awareness of the results, Dr. Collins said. Under a pair of related proposals announced by NIH officials, researchers will be given specific guidelines on which trials are covered by the rules and which penalties will be levied against researchers who fail to comply. The current law is unspecific, NIH officials said. That has left researchers uncertain ­— or able to claim uncertainty — about the law’s exact requirements.

Once the new rules take effect, "it will be a straightforward matter for us to be able to take compliance action," said Kathy L. Hudson, deputy director of science, outreach, and policy at NIH. The policy consists of two sets of complementary rules, one largely covering medical-trial results presented to the U.S. Food and Drug Administration as part of a drug-approval process, and the other covering research financed by the NIH.

In the case of the FDA, violations would lead to civil penalties. In the case of the NIH, researcher noncompliance could lead to the withholding of grant money, and loss of future agency support, Ms. Hudson said. "We’re certainly going to be taking that into account as we decide about future grant awards," she said of researcher-compliance records. The rules were issued with the expectation that they will take effect after a 90-day period of public comment…
Here’s the official press briefing:
National Institute of Health
News Release
November. 19, 2014

The U.S. Department of Health and Human Services today issued a Notice of Proposed Rulemaking [NPRM], which proposes regulations to implement reporting requirements for clinical trials that are subject to Title VIII of the Food and Drug Administration Amendments Act of 2007 [FDAAA]. The proposed rule clarifies requirements to clinical researchers for registering clinical trials and submitting summary trial results information to ClinicalTrials.gov, a publicly accessible database operated by the National Library of Medicine, part of the National Institutes of Health. A major proposed change from current requirements is the expansion of the scope of clinical trials required to submit summary results to include trials of unapproved, unlicensed, and uncleared products.

“Medical advances would not be possible without participants in clinical trials,” said NIH Director Francis S. Collins, M.D., Ph.D. “We owe it to every participant and the public at large to support the maximal use of this knowledge for the greatest benefit to human health. This important commitment from researchers to research participants must always be upheld.”

ClinicalTrials.gov currently contains registration information for more than 178,000 clinical trials and summary results for more than 15,000. These numbers include trials that are not subject to FDAAA. Among the primary benefits of registering and reporting results of clinical trials, including both positive and negative findings, is that it helps researchers prevent unnecessary duplication of trials, particularly when trial results indicate that a product under study may be unsafe or ineffective, and it establishes trust with clinical trial participants that the information from their participation is being put to maximum use to further knowledge about their condition.

Developed by NIH in close coordination with the FDA, the proposed rule details procedures for meeting the requirements established by FDAAA to improve public access to clinical trial information. FDAAA and the proposed rule apply to certain interventional studies of drugs, biological products, and devices that are regulated by the FDA, but, generally, not to phase 1 trials of drugs and biological products and small feasibility studies of devices. The proposed rule specifies how data collected and analyzed in a clinical trial would be required to be submitted to ClinicalTrials.gov. It would not affect requirements for the design or conduct of clinical trials or for the data that must be collected during clinical trials.

“This proposed rule would close an important gap, making additional information about clinical studies of investigational drugs, medical devices and biological products available to the public,” said FDA Commissioner Margaret A. Hamburg, M.D. “It would help eliminate unnecessary duplicative trials, advance biomedical innovation, and provide the public with a much richer understanding about the clinical trials for these products.”

Notable changes from current requirements and practice that are outlined in the proposed rule include:
  1. A streamlined approach for determining which trials are subject to the proposed regulations and who is responsible for submitting required information.
  2. Expansion of the set of trials subject to summary results reporting to include trials of unapproved products.
  3. Additional data elements that must be provided at the time of registration [not later than 21 days after enrolling the first participant] and results submission [generally not later than 12 months after completion].
  4. Clarified procedures for delaying results submission when studying an unapproved, unlicensed, or uncleared product or a new use of a previously approved, licensed, or cleared product and for requesting extensions to the results submission deadline for good cause.
  5. More rapid updating of several data elements to help ensure that users of ClinicalTrials.gov have access to accurate, up-to-date information about important aspects of a clinical trial.
  6. Procedures for timely corrections to any errors discovered by the responsible party or by the Agency as it processes submissions prior to posting.
Read a summary of the proposed changes here.
Here it is rolled out by the NIH top brass:
by Kathy L. Hudson, PhD and Francis S. Collins, MD, MPH
November 19, 2014
Here is Ed Silverman’s take on it:
Pharmalot: WSJ
by Ed Silverman
November 19, 2014
And here’s the Science Insider:
Science: Science Insider
by By Jocelyn Kaiser
November 19, 2014
I’ve spent months following the European Medicines Agency [EMA] deliberations about Data Transparency in Clinical Trials. In fact, my project that takes me away from blogging is about that same issue. I know I’ve written about a lot of things along the way in these blogging years, but this is the most important issue in my own mind. Somewhere along the way, a conduit got opened and the medical literature became corrupted by industry and academic articles whose agenda were something other that the advancement of medical science. My specialty, psychiatry, was heavily afflicted – filled with jury-rigged experimercials and questionable Clinical Trial results, equally questionable review articles, and industry contaminated CME material, all of which were aimed at corporate profits, not doing the job of caring for the sick. If the NIH and FDA really do everything they say here, they would be starting a ball rolling down the rightest of hills to begin cleaning up this wrongest of circumstances. And speaking of about time, it’s long overdue – but a welcome move in the very rightest of directions…
    Bernard Carroll
    November 20, 2014 | 4:01 AM

    Hmmm… maybe Newsweek had an inkling of this when they ran last week’s story. If so, good for them.

    Steve Lucas
    November 20, 2014 | 6:50 AM

    This link caught my attention:


    My local paper touted this as a major break through in cardiac care. The numbers do not bare this out as the NNT and cost becomes less than optimal. In another article the cost were some where in the neighborhood of $770,000 to possibly prevent one MI. looking at this as a number problem only a MI cost $30,000 to treat.

    Data becomes the first link in a clearer picture of drug effectiveness and cost.

    Steve Lucas

    November 20, 2014 | 3:20 PM

    I can’t help but Think this is something of a step in the right direction.
    But nothing is implemented yet, nothing has in fact changed.
    And since so many scientists, professors and MD’s have fully accepted the old, very faulty system, Little will infact ever change for those that suffer from faulty medication.
    Even though most professors and scientists are mearly human, they are, on average, more intelligent than the rest of us.
    And the old set of rules was scarily stupid, to me, the common man.
    I would not have accepted those rules, but they did.

    And I like to Think that you who advocate more transparency are also thinking of those that in the end will come to use the Pharmaceuticals?
    Or is this just a play amongst academics?

    James O'Brien, M.D.
    November 20, 2014 | 4:48 PM

    There’s some doublespeak in that article. The rules were in place, but they weren’t enforced. So the solution is new rules, which sound like rules to do a better job enforcing by website submission. Doesn’t sound like you need new rules, sounds like you need someone in the executive branch to care. Wonder who was paying them not to care? My experiences with government databases is that they don’t really work that well anyway.

    So the executive branch wants to come off as caring when all along the demonstrate by their actions that they don’t…

    More rules are not a solution to lack of enforcement…it just makes it tougher to enforce…

    Bernard Carroll
    November 20, 2014 | 5:33 PM

    Right. Here is a comment I made on the Pharmalot blog about enforcement: “Is it just me or are others also uncertain whether these new regulations apply to corporate studies? The HHS announcement spoke generically of “clinical researchers” but most of the announcement seemed to be directed at NIH grantees. Will the FDA have leverage over the reporting of corporate trials? How will that work? I think this needs to be specifically nailed down during the public comment period.”

    berit bryn jensen
    November 20, 2014 | 6:36 PM

    …”starting the ball rolling … to cleaning up the wrongest of circumstances”…
    Long overdue, to be followed closely, to see that it truly does what it purports doing, which the government must enforce, in order to fulfill the social contract of caring for the sick and the vulnerable.
    At a governmental conference here today, a question was raised from the rostrum, by a professor of law speaking on justice, security and patient trust: “Can psychiatry be trusted?” The answer is no, unless there is openness, transparency and humility faced with the great unknown areas of human brains, minds and the rich variety of mankind.
    Thank you, dr Nardo, for your great work in keeping readers up to date and informed and some of us hopeful that the juggernaut may be tamed.

    James O'Brien, M.D.
    November 20, 2014 | 9:01 PM

    Experience has shown the most social order and harmony when there are few easily understood rules that are universally and fairly enforced. When you have thousands of regulations and intermittent variable enforcement, what you get is anarchy and chaos and cronyism that favors big business and institutions (witness the small fines on big pharma and big banks). I don’t think a lot of people in Washington understand this. Or maybe they do, which leads one to conclude we are living in a kleptocracy.

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