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posted by martyb on Monday April 10 2017, @09:17AM   Printer-friendly
from the draw-curve-then-select-points-to-plot dept.

Scott Gottlieb, President Trump's nominee to run the FDA, is a proponent of adaptive clinical trials, which would allow adjustments of trials as they are ongoing:

In 2006, Scott Gottlieb, then a deputy commissioner at the U.S. Food and Drug Administration (FDA), stood before an audience of clinicians and researchers to sing the praises of a new approach to drug trials. Instead of locking in a study's design from the start, researchers could build in options that would allow them to adjust along the way, based on the data they had collected. They could make the trial larger or smaller, for instance, add or remove arms, or change how incoming patients get assigned to them. Gottlieb predicted such adaptive trial designs, the topic of the conference he attended that distant summer in Washington, D.C., would "tell us more about safety and benefits of drugs, in potentially shorter time frames."

This week, as President Donald Trump's nominee to head FDA, Gottlieb sat before Republican lawmakers hungry for promises of "shorter time frames" for drug and device approvals, and again expressed his zeal—repeatedly—for adaptive trial designs. If confirmed to be FDA's head, as expected, Gottlieb suggested he'd promote wider use of the approach.

But for all their promise, many adaptive trial features still aren't commonplace. And Gottlieb will face a number of obstacles to encouraging their wider use, experts tell ScienceInsider.


Original Submission

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Politics: Koch-Backed Groups Urge Congress to Pass "Right to Try" Legislation 56 comments

Groups funded by Charles and David Koch have launched ad campaigns aimed at urging Congress to pass legislation that would make it easier for terminally ill patients to try experimental treatments. The bill passed the Senate unanimously, but FDA Commissioner Scott Gottlieb told the House in October (archive) that the FDA already approves 99% of requests for expanded access/compassionate use, and that the primary roadblock is not the FDA, but drug supply constraints. He said that pharmaceutical companies do not continuously manufacture a drug undergoing clinical trials, but instead produce "discontinuous batches":

Several deep-pocketed political advocacy groups founded by Charles and David Koch are ramping up their advocacy before Congress on a niche issue: access to experimental drugs.

On Monday, several Koch-backed groups, including Freedom Partners and Americans for Prosperity, launched an ad campaign urging Congress to pass so-called "right-to-try" legislation, which aims to help terminally ill patients access experimental treatments that haven't yet been approved by the Food and Drug Administration. The Senate unanimously passed a right-to-try bill from Sen. Ron Johnson (R-Wis.) last August, but it has since stalled in the House. Supporters, including lawmakers on Capitol Hill and other off-the-Hill advocates, are focusing their efforts this month on the Energy and Commerce Committee, which would likely have to clear the legislation before the full House could vote on it.

The new ad campaign — also sponsored by Generation Opportunity and The LIBRE Initiative — directly addresses Congress, saying at the end of one commercial, "Congress, give patients a chance. Pass right to try." In addition to a series of digital ads focused on D.C. and key congressional districts, the campaign will include lobbying efforts by the groups, according to a press release. In a letter sent Monday to Committee Chairman Greg Walden (R-Ore.), executives wrote, "We strongly urge your committee to act expeditiously to approve Right to Try legislation and send the bill to the House Floor for a full vote."

Johnson told STAT he's doing everything he can this month to get the legislation passed, and suggested the vice president might become even more engaged. Vice President Mike Pence has supported right-to-try efforts since he signed a similar law as governor of Indiana.

S.204 - Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017

Related: What a Gottlieb-Led FDA Might Mean for the Pharmaceutical Industry
FDA Nominee is a Proponent of "Adaptive Trials"
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University Could Lose Millions From "Unethical" Research Backed by Peter Thiel
"Black Hole" of Accountability for Drug Trials Flouting FDA Oversight?
Drug Approvals Sped Up in 2017


Original Submission

Former FDA Commissioner Scott Gottlieb Joins Pfizer Board of Directors 14 comments

Scott Gottlieb walks through the revolving door to the Pfizer board

The revolving door turns again. After a two-year stint running the Food and Drug Administration, Scott Gottlieb has joined the board of directors at Pfizer, giving the world's largest drug maker crucial insights into the inner workings of the Trump administration as it attempts to contain national angst over the rising cost of medicines.

And in doing so, Gottlieb is also picking up where he left before joining the agency, since he had been on the board of several smaller pharmaceutical companies and was also a partner at a venture capital firm that invests in life sciences companies.

"This is classic and it's not surprising," said Sidney Wolfe, a founder of Public Citizen Health Research Group and a long-time FDA watchdog, who had expressed concern about Gottlieb's ties to industry before joining the agency. "Philosophically, he's returning to the ecosystem where he's most comfortable. And he'll get paid very well for it, too."

Also at Financial Times.

Related: What a Gottlieb-Led FDA Might Mean for the Pharmaceutical Industry
FDA Nominee is a Proponent of "Adaptive Trials"
Drug Approvals Sped Up in 2017
Koch-Backed Groups Urge Congress to Pass "Right to Try" Legislation
FDA Labels Kratom an Opioid
FDA Has Named Names of Pharma Companies Blocking Cheaper Generics [Updated] (including Pfizer)
U.S. to Make More Drugs Easily Available, Cutting Role Docs Play


Original Submission

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  • (Score: 2) by bradley13 on Monday April 10 2017, @09:48AM (14 children)

    by bradley13 (3053) on Monday April 10 2017, @09:48AM (#491566) Homepage Journal

    Why is this of relevance? A quick skim of what an adaptive trial is all about, and...sounds like a variation that would be appropriate in some circumstances. Adapting a trial in progress requires extra care not to mess up the trial results. An example might be discovering the dosage limits of a medicine: successively increasing/decreasing dosage until some effect appears/disappears. Really, a rather minor point.

    If this is the most important issue to be discussed, I suppose the guy will be approved with no problems?

    --
    Everyone is somebody else's weirdo.
    • (Score: 3, Insightful) by GungnirSniper on Monday April 10 2017, @11:27AM

      by GungnirSniper (1671) on Monday April 10 2017, @11:27AM (#491581) Journal

      Republicans will speak to their base of the business benefits, and Democrats will speak to their base of the safety concerns. He will be approved, but both sides need to use his carcass for promotion first.

      Pharma is one area were we probably have too much regulation now in response to the free-wheeling problems that created weight loss drugs with long-term side effects, or "thalidomide babies" with missing limbs or "flippers". So the balance of cost and risk is eternally in play.

    • (Score: 5, Insightful) by FatPhil on Monday April 10 2017, @12:12PM (5 children)

      by FatPhil (863) <pc-soylentNO@SPAMasdf.fi> on Monday April 10 2017, @12:12PM (#491597) Homepage
      It also permits p-hacking.
      --
      Great minds discuss ideas; average minds discuss events; small minds discuss people; the smallest discuss themselves
      • (Score: 1) by Zipf on Monday April 10 2017, @05:29PM (1 child)

        by Zipf (2400) on Monday April 10 2017, @05:29PM (#491760)

        This is true -- buy only if those who conduct the trail are unaware of p-hacking. (they are not.)

        I found the following to be rather enlightening:

        http://www.intelligencesquaredus.org/debates/fdas-caution-hazardous-our-health [intelligencesquaredus.org]

        Gottlieb and Huber basically convince those who argue against adaptive trials that adaptive trials are what we need.

        • (Score: 2) by FatPhil on Tuesday April 11 2017, @08:30AM

          by FatPhil (863) <pc-soylentNO@SPAMasdf.fi> on Tuesday April 11 2017, @08:30AM (#492179) Homepage
          > This is true -- buy only if those who conduct the trail are unaware of p-hacking

          or are *perfectly aware* of p-hacking

          > (they are not [unaware].)

          you're close to working out the problem now.
          --
          Great minds discuss ideas; average minds discuss events; small minds discuss people; the smallest discuss themselves
      • (Score: 2) by AthanasiusKircher on Monday April 10 2017, @05:53PM (1 child)

        by AthanasiusKircher (5291) on Monday April 10 2017, @05:53PM (#491776) Journal

        Does this really qualify as "p-hacking"? P-hacking generally implies taking existing data and trying out oodles of possible statistical correlations to find one (or more) that appear to have a "significant" result. (Or other equivalent data analysis methods than obscure the experimental design and data collection in such a way as to overestimate significance.)

        But this isn't a post-hoc statistical analysis procedure. This is actively manipulating the study and data collection while in progress. I think this actually falls on a different level of study manipulation than p-hacking (which is generally referring to the analysis phase).

        There may be times when an adaptive procedure is justified, but each adaptation generally decreases statistical power and makes it less likely the study the results will mean anything. A rigorous statistical analysis should actually determine that most adaptive studies have LESS significant results, which would be the opposite of p-hacking. (Note that I'm relying on the idea that researchers would honestly report their method and results.)

        The main way to combat p-hacking is to specify analysis methods in advance, rather than allowing ad hoc data manipulation after-the-fact. The effects of potential adaptation may also be able to be quantified in advance (depending on exactly what sort of adaptation is allowed), along with their subsequent effect on the statistical power. But a better design might generally be to use an adaptive trial to identify potential good treatment procedures and then design a more rigorous second study to verify with a locked-down a priori procedure and data analysis method.

        But I'm assuming your point was that a bad use of adaptive design is to fudge the experimental method as you go but analyze the data as if nothing weird happened (which might inflate significance). Yeah, that's the way I'd be afraid of drug companies "cheating" too, though I don't know if I'd call that p-hacking in the normal sense. That would, to me, qualify as more active direct study manipulation, more easily rising to the level of deliberate professional misconduct. If this is done correctly, the parameters of adaptive studies would need to be built into the proposed study design in advance, as well as their potential impact on the way the results are handled.

        • (Score: 2) by FatPhil on Tuesday April 11 2017, @08:39AM

          by FatPhil (863) <pc-soylentNO@SPAMasdf.fi> on Tuesday April 11 2017, @08:39AM (#492184) Homepage
          There are several ways to p-hack. One is post-hoc trawling for relevance in a huge pool of data. Another is simply by running multiple experiments, and chosing (stopping at) the one that has the desired outcome. That latter form is probably the more familiar form of p-hacking: https://www.xkcd.com/882/ Changing the experiment is creating more experiments. (And introducing more flexibility to delete outliers.)
          --
          Great minds discuss ideas; average minds discuss events; small minds discuss people; the smallest discuss themselves
      • (Score: 0) by Anonymous Coward on Monday April 10 2017, @07:47PM

        by Anonymous Coward on Monday April 10 2017, @07:47PM (#491887)

        My Pee doesn't have an interface, not even a USB port... I tested it no wifi hotspot either, so good luck!

    • (Score: 4, Insightful) by MrGuy on Monday April 10 2017, @12:54PM (2 children)

      by MrGuy (1007) on Monday April 10 2017, @12:54PM (#491606)

      Adapting a trial in progress requires extra care not to mess up the trial results.

      Another way of putting this point is that when you adapt a trial in progress, it's very easy to bias the results. You have to be both intellectually honest and scientifically rigorous to avoid this.

      Allowing adaptive trials will increase efficiency in scientific testing and reduce time to market if drug makers work hard to avoid bias. They will reduce safety and lead to getting dangerous drugs approved and into the market if they don't.

      The FDA's role in the process is to ensure drugs are safe. The concern is that, given the current administration's focus on reducing regulatory oversight, the FDA will lack either the authority or the will to ensure such trials are conducted responsibly, and not used by companies to cheat.

      • (Score: 3, Insightful) by Immerman on Monday April 10 2017, @01:29PM (1 child)

        by Immerman (3985) on Monday April 10 2017, @01:29PM (#491611)

        Indeed. It's an strategy that is much better suited to "exploratory" research, which is what most medical testing is. However, it does make intentionally biasing the studies easier, and there is already plenty of evidence of repeated dishonest testing by the big pharmaceutical companies.

        I could see it working well if we also complemented it by adding the requirement for independent verification of the results before approval. Verification can readily test only the narrow final claims. Just loosening the scientific rigor of the standards though seems like a bad idea.

        On the other hand - pharmaceutical companies already cheat routinely, so it could be argued that there isn't actually anything lost.

        Perhaps an encouragement to honesty with lower overhead - such as large mandatory fines for any company found to have falsified data or otherwise unfairly biased their research, intentionally or otherwise. Encourage independent review within the company. Make the fines payable directly to the FDA coffers in order to discourage corruption at least at the institutional level.

        • (Score: 2) by MrGuy on Monday April 10 2017, @02:27PM

          by MrGuy (1007) on Monday April 10 2017, @02:27PM (#491638)

          On the other hand - pharmaceutical companies already cheat routinely, so it could be argued that there isn't actually anything lost.

          I think there's a huge difference when, facing a class action lawsuit, a company can claim "We conducted rigorous scientific studies using industry standard methods overseen and approved by the FDA!" As opposed to "You caught us - we fudged the numbers to get the result we wanted and lied about it in our reports."

          It might not reduce liability to zero, but being able to claim with a straight face that you did a scientifically accurate study and the FDA oversaw and approved it is a pretty good defense.

    • (Score: 2) by DannyB on Monday April 10 2017, @03:49PM

      by DannyB (5839) Subscriber Badge on Monday April 10 2017, @03:49PM (#491681) Journal

      Nothing wrong with an adaptive trial if the people doing it are "adapting" it for honest and ethical reasons.

      Therein lies the highly likely problem.

      New Clinical Study Shows Promise. People can be happy and enjoy the rest of their lives with high doses of morphine and arsenic! Who knew!

      Trump directs FDA to expedite approval with executive order.

      --
      If we tell conservatives that the climate is transitioning, they will work to stop it.
    • (Score: 2) by davester666 on Monday April 10 2017, @07:59PM (2 children)

      by davester666 (155) on Monday April 10 2017, @07:59PM (#491894)

      The new "adaptive" means they can just remove the people who die and/or get ill from the study, so that the medication can be approved based on the initial trial. They don't have to keep doing it over and over until they get the results needed for approval (and burying the "bad" trials with attorney-client privilege)...

      • (Score: 2) by FatPhil on Tuesday April 11 2017, @08:42AM

        by FatPhil (863) <pc-soylentNO@SPAMasdf.fi> on Tuesday April 11 2017, @08:42AM (#492186) Homepage
        > The new "adaptive" means they can just remove the people who die

        "Outliers" in statistical terminology.
        --
        Great minds discuss ideas; average minds discuss events; small minds discuss people; the smallest discuss themselves
      • (Score: 1) by purple_cobra on Wednesday April 12 2017, @08:30PM

        by purple_cobra (1435) on Wednesday April 12 2017, @08:30PM (#493050)

        See Ben Goldacre's various media interviews/appearances and his book 'Bad Pharma' (he also wrote 'Bad Science') for more on this kind of thing; he was pretty vocal about Tamiflu, amongst other useless drugs.

  • (Score: 5, Insightful) by BsAtHome on Monday April 10 2017, @09:52AM (2 children)

    by BsAtHome (889) on Monday April 10 2017, @09:52AM (#491567)

    Rough translation: When a trial is adaptable, then we must correct the course in such a way that our biases and preconceptions are confirmed. There is no real point in doing profitable drugs and studies when your hypothesis is rejected. That only costs money and is not something we like.

    There are, of course, rigorous methods to do adaptive trials correct, but I doubt that rigor is the goal for big pharma. Give them a finger and they will grab your hand.

    The correct course of action, IMHO, is to have all studies in the open from conception to result. No study should be allowed to meander the path of favoritism for any particular result, especially not when the study may change the parameters.

    • (Score: 0) by Anonymous Coward on Monday April 10 2017, @01:59PM (1 child)

      by Anonymous Coward on Monday April 10 2017, @01:59PM (#491624)
      What you are calling is really for FDA oversight. The FDA, as a federal agency, should a) allow for adaptive trials in order to attempt to speed drug development timelines while b) making sure that the companies doing the trials aren't p-hacking or otherwise biasing the results. The JOB of the scientists at the FDA is to perform this task.
      • (Score: 3, Insightful) by DannyB on Monday April 10 2017, @03:51PM

        by DannyB (5839) Subscriber Badge on Monday April 10 2017, @03:51PM (#491684) Journal

        What is this "oversight" word you speak of? Are you referring to some kind of burdensome business-killing regulations?

        --
        If we tell conservatives that the climate is transitioning, they will work to stop it.
  • (Score: 1) by gumby on Monday April 10 2017, @03:57PM (1 child)

    by gumby (3079) on Monday April 10 2017, @03:57PM (#491690)

    As someone who has appeared before the FDA and has designed trials approved for human experimentation: this is not new, and it's promising in principle, though not remarkable, that Gottleib is interested in this. The agency has long been concerned about the time, cost and complexity of the approval process and has supported experimentation in this area. However they are also rightfully quite conservative and won't adopt a Silicon Valley-level of experimentation. Which, as someone who takes medicine frustrates me but even more makes me thankful.

    • (Score: 0) by Anonymous Coward on Monday April 10 2017, @04:35PM

      by Anonymous Coward on Monday April 10 2017, @04:35PM (#491714)

      Fortunately, conservatives are prepared to be liberal when there's $$$$$$ to be made.

  • (Score: 0) by Anonymous Coward on Tuesday April 11 2017, @10:56AM

    by Anonymous Coward on Tuesday April 11 2017, @10:56AM (#492212)

    Pray I do not adapt it any further.

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