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Academia (vs. Industry)

Getting Around to Reporting Clinical Data, Real Soon Now

Science has an interesting report on the publication of clinical trial results. Some readers will recall similar efforts from 2015 and 2017/2018 in the US and Europe; this is actually a follow-up by one of the same US authors. It should actually be a dull report, because the requirements for such disclosure are clear. The rules have been gradually tightened up over the years, most recently in 2017, and in January 2018 penalties went into effect for trials that are registered on Clinicaltrials.gov but whose results are not subsequently made public.

The article looks at 4700 trials what should have reported already under this law. It does seem to have improved disclosure rates, but it also seems as if there has been no enforcement whatsoever, so you wonder how long that improvement will last. We know that enforcement has been lax because there are many institutions that have had all sorts of difficulties fulfilling their obligations. That was the case in the earlier report, too, but it has to be said that some of the laggards in that one have picked up the pace. Sloan-Kettering, Duke, and Johns Hopkins did not look good in the 2017 figures, but have improved greatly. Who hasn’t? Obscure little outfits like M. D. Anderson, the Mayo Clinic, and UCSF have the great majority of their eligible trials marked as reported late or not reported, and there are plenty of others. The University of Virginia, for example has been involved in 23 trials that should have been reported, and the great majority of them haven’t even gotten as far as reporting late: they mostly haven’t shown up at all, showing an overall average of about nine months late and growing by the day. Yale has run 19 trials that should have reported during this period; only three have done so on time.

Even the federal government itself doesn’t come across looking very good. The National Institute of Allergy and Infectious Disease has reported over half its trials on time, but the rest of NIH hasn’t. Of those, National Heart, Lung, and Blood Institute is showing the lowest percentage of on-time reporting in the entire table, an impressive showing if you just ignore the minus sign in front of it. But if the NIH doesn’t bother to report its own work on time under the legal provisions of its own web site, it’s hard to see why anyone else should.

But do you know who does? The biopharma industry. The article’s charts are broken down by category (academia, government, and industry), and the absolute worst pharma company on the list is Teva. By a wide margin. But they would be one of the better ones on the other two lists. There are several companies with perfect records, and only one (Sanofi) that has a single trial that has not reported yet. Few non-industrial organizations even come close.

I should note that this was the same in the earlier looks at clinical trial reporting. For all the talk of drug companies burying trial results, industry actually seems to be taking its reporting responsibilities far more seriously than academia. Or the government itself. The new FDA commissioner used to be the chief medical officer at M. D. Anderson, the majority of whose 89 trials have reported late or not at all (averaging 128 days behind schedule). Is he the person who will bring things into line, do you think? Or will the agency just wag its finger a bit harder?

26 comments on “Getting Around to Reporting Clinical Data, Real Soon Now”

  1. electrochemist says:

    The Federal Government is like HR: good at making rules for others, but generally unwilling to follow its own rules….

    1. anon the II says:

      Aren’t rules always designed for someone else?

  2. A Nonny Mouse says:

    Probably because pharma can afford the expensive software which has kept my wife in employment for the last 25+ years (Teva aren’t her favourite!).

    1. Hap says:

      If academic institutions can’t handle trial data, they have no business doing a trial. If they can handle the data, then they should have no legitimate problem submitting it, since they have to plan on submitting it somewhere (unless they expect the trial to fail, in which case, why have a trial at all) and so should have the ability to handle and submit the data. (No, “I don’t want to” doesn’t count as a legitimate reason. Things that don’t past muster coming from four year-olds shouldn’t fly from sixty four-year olds.)

  3. mallam says:

    Is there a possible penalty for non-compliance? Without a substantial negative incentive, why would practices change?

    1. Punish the Unpunishable? says:

      What would the penalty be? Do you really think it’s possible to meaningfully punish government employees and tenured faculty?

      1. Dylan Richards says:

        Maybe they could add a new policy that with new clinical trial enrollment forms/agreements, they have to put the number of report trials versus unreported trials on the enrollment information, so then patients/doctors know how transparent the company is or how thorough they are. Most people don’t willingly go to restaurants with C ratings, right?

      2. John Thacker says:

        It’s very easy to punish academics in this case, by simply making it harder or impossible to get grant funding, whether on a personal or institutional level. For the government agencies, though, quis custodiet ipsos custodes is always a problem.

  4. Eugene says:

    From the Science article, there financial penalties, but that puts the FDA in the interesting position of fining the NIH or an Academic intstitution who is conducting a study with a government grant. Does the grant money pay for the cost of reporting or fines?

  5. loupgarous says:

    “Obscure little outfits like M. D. Anderson, the Mayo Clinic, and UCSF have the great majority of their eligible trials marked as reported late or not reported, and there are plenty of others.”

    I wonder if M.D. Anderson’s managed to retract all of Bharwat Aggarwal’s papers which required a little “help” making a case that turmeric and other ayurvedic medications were effective against cancer.

    “M.D. Anderson confirmed in 2012 that it had launched the review after the U.S. Department of Health and Human Services’ Office of Research Integrity notified the institution that academic whistleblowers had raised questions about 65 published papers by Aggarwal. The federal office declined comment on its role in the matter. The whistleblowers alleged Aggarwal manipulated study images – adding or subtracting features and cropping, stretching, rotating and flipping them horizontally or vertically – to leave the impression the same ones represented different experimental conditions.

    So there’s that with M.D. Anderson, too.

    1. loupgarous says:

      Pardon me, the man’s name is Bharat Aggarwal, and curcurmin was the component of turmeric whose biochemical properties Aggarwal investigated. Retraction Watch said back in 2015 that Biochemical Pharmacology retracted 7 of Aggarwal’s papers in one go.
      Wikipedia’s article “Bharat Aggarwal” mentions that by 2019, 28 papers published by Aggarwal were retracted, ten others received an expression of concern, and 17 others were corrected. So, M.D. Anderson’s staff may have been facing a backlog of work just helping clear all that up, given the Houston Chronicle reported that M.D. Anderson told them 65 of Aggarwal’s papers had been mentioned by academic whistleblowers as being potentially problematic.

    2. Frank says:

      There are strong incentives for hospitals and investigators to initiate trials (even it is not based on science/rationale) : grant, prestige, industry-relationship, etc…
      There are no incentives for them to publish negative results, other than it is clear disservice to the patients who participated in the trial

      1. smurf says:

        I think you should explain why publishing a negative result is a disservice to patients.

        1. matt says:

          Have you ever participated in a trial? Yes, if you have some condition, you want a miracle cure. But, failing that, you desperately want the science to move forward, for people to know more, so even if your outcome isn’t good, somewhere down the line we know more next time so other people eventually see a benefit. If we don’t learn, fifty years later people will still have the same dismal prospects (eg, if you have glioblastoma, or Alzheimer’s, or pancreatic cancer). Many people want a trial to help change that, to give some glimmer of meaning to their condition, however weak it may be.

          Negative results are a necessary part of that change. Other than a lucky hit on the exact right path, there’s no way to prune the possibility tree, except by eliminating the obvious branches that turned out to be dead ends. Those dead ends are giving real corrections to our garbled thinking, or perhaps the thinking is fine, but the implementation is garbled.

          1. loupgarous says:

            Well put. I have taken part in a few clinical trials – among them, the ones that led to FDA approval of LutaThera (lutetium-177 dotatate) and Ga-68 dotatate imaging for neuroendocrine cancer. I was active in clinical data processing for Big Pharma firms long before those studies and have seen my share of negative results. My clients dutifully reported the bad news and the good news about the products in the trials I helped process.

            So, I was under no illusions about a cure for my neuroendocrine cancer – there are no certainties in life, and I could well have been a non-responder to an investigational therapy for a number of reasons. However, existing therapy wasn’t helping me much.

            At my medical oncologist’s advice, I went on clinicaltrials.org and found the PRRT study, and enrolled. My reasoning? Even negative results are valuable. They say “Well, that didn’t work. Let’s see what we did wrong.” But I’m happy that my metastatic disease is stable, and that it’s more stable than it was this time last year. And my progress is being monitored by Ga-68 PET, for which I was also a clinical trials subject.

            I won’t lie and say I’d have been just as happy if either PRRT or Ga-68 PET hadn’t worked for me. I am happy to have been able to help the process of finding new therapies for a rare family of cancers which is now being treated and diagnosed more reliably than before.

        2. Frank says:

          There is absolutely requirement to publish the results (negative or not). I’m making a point that some institutions/PIs don’t publish because the data does not support their next grant writing, which is a disservice to the patients and waste of more resources…

      2. loupgarous says:

        You’re right. Experimental data contradicting therapeutic claims for curcurmin and other ayurvedic remedies were systematically covered up by Bharat Aggarwal at M.D. Anderson. It took notice from DHHS’ Office of Research Integrity of questions about 65 published papers by Aggarwal before M.D. Anderson conducted an in-house review. This may be an extreme case, but it does show that even reputable research centers have problems reporting negative results, and that it’s not Pharma doing this – it’s academe.

  6. Emjeff says:

    This is one of the reasons why so many people have such disdain for the Federal Government. Recall that this requirement was put into place because of the concern that the pharmaceutical industry was hiding results. Well, I’ll ask this question: Academia what are YOU hiding?

  7. annon says:

    I used to know some physicians who run clinical trials. They told me clinical trials do not genertate enough revenue for the hospital. There is no financial incentive to follow up.

  8. loupgarous says:

    “For all the talk of drug companies burying trial results, industry actually seems to be taking its reporting responsibilities far more seriously than academia. Or the government itself. The new FDA commissioner used to be the chief medical officer at M. D. Anderson, the majority of whose 89 trials have reported late or not at all (averaging 128 days behind schedule). Is he the person who will bring things into line, do you think?

    .This is just one of several troubling appointments by this administration in the health and fitness sector. The President’s Council on Sports, Fitness & Nutrition includes Bill Belichick and Mehmet Oz.

  9. Greg says:

    A similar dismal outcome for Academia vs Industry comparison in the EU was reported last in year in ‘Nature’: European universities dismal at reporting results of clinical trials (https://www.nature.com/articles/d41586-019-01389-y)

  10. MrXYZ says:

    I wonder if SEC requirements put pressure on public companies to disclose clinical trial data, since success or failure can materially affect the valuation of a company. Can anyone comment further on that?

    1. rnt says:

      I worked many years in clinical research at a large pharma company. I’ve also worked in academics also doing clinical trials. I think the main reason there is such a large difference is simple; pharma companies have large staffs devoted completely to compliance. Reporting results into clintrials.gov is right up their alley. In contrast, clinical trials in academia are running with much smaller staffs, turnover is higher, and reporting results is just not high priority. I’m not defending the low rate but most academics don’t put a high value in this.

    2. loupgarous says:

      Please re-read the article. The people who are late with clinical trial results or haven’t published them at all are primarily academic researchers, not pharma industry workers.

      You don’t bring SEC in to do what FDA already does a good job of, requiring Big Pharma’s clinical trial results to be published and in order and and the data on which they are based available for verification before each new drug is approved to be sold in the United States.

      SEC punishes “forward-looking statements” that turn out to be BS and mislead investors, and that is where a very few Big Pharma firms ought to feel their ears burning as I type this. FDA is very strict with pharma already about publication of clinical trials (except for a gaping exception granted by the “Right to Try” law).

      FDA and NIH need to turn up the heat under academic researchers and healthcare providers who aren’t documenting their clinical trials properly, or like M.D. Anderson’s former researcher Bharat Aggarwal (with at least 28 retractions) totally pencil-whipping their drug-related research. By comparison, Big Pharma does a good job on reporting their clinical trial outcomes because their earnings already depend on doing a good job and being seen to have done a good job.

  11. Anonymouse says:

    Someone can correct me if I am wrong/misremembering/outdated, but couldn’t some of the low academic response rate be due to the NIH choosing to classify a large proportion of basic research (at least in psych) as clinical trials? If a basic science fMRI study comparing brain region activation of (eg) looking at cats vs houses is forced to register as a clinical trial is it surprising that no one follows up on that?

    tbh I am out of the loop and maybe the NIH backed off on requiring all of these passive studies to register as trials, or maybe they are too few to change the numbers

    Eg this link: https://www.sciencemag.org/news/2017/08/basic-studies-how-our-brains-work-are-now-clinical-trials-nih-says

  12. avantika says:

    I think that there definitely should be a penalty for those professionals and organisations who do not report trials . They must adhere to the need of the hour. Thanks for sharing this informative post.

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