On transparency of clinical trials

by Alexey Bersenev on February 10, 2013 · 3 comments

in Uncategorized

More and more clinical trials are getting registered in public databases. Partly, because it’s mandated by government agencies, but also because of our understanding the importance of information transparency. I’d speculate that now most of cell therapy clinical trials get registered in databases. But how good are we at posting results and analyzing the data from these trials? Unfortunately, we are very bad at it:

The best evidence shows that half of all the clinical trials ever conducted and completed on the treatments in use today have never been published in academic journals. Trials with positive or flattering results, unsurprisingly, are about twice as likely to be published — and this is true for both academic research and industry studies.

The studies, supported this evidence were published in PLoS (1/2).

The problem is that the results of trials are hidden deliberately. Even though FDA Amendments Act of 2007 required to post results of all trials, registered in ClinicalTrials.gov, within a year after completion, nobody follows the rule.

The price that we pay for this non-transparency could be horrific:

This cannot be acceptable. Withholding data not only misleads doctors and patients; it’s an insult to the patients who have participated in clinical trials, believing that they were helping to improve medical knowledge.

Unfortunately, it’s not just a problem of BigPharma. The situation with cell therapy trials is not better. According analysis of Emily Culme-Seymour, less than 1% of cell therapy trials have results posted in database:
http://twitter.com/cells_nnm/status/197412760806625283

When I narrowed down a search to “stem cell” and to the last 2 years, I was able to find only 5 trials with posted results:
NCT00145587
NCT00203203
NCT00684060
NCT01193660
NCT01110252

No results were posted from industry-sponsored trials. Please note, that currently, only NCT platform allow to post results. But this database takes > 70% of all international registries in cell therapy. So, we don’t have posted results not because of web-platform limitation, but because of unwillingness of professionals to do it.

Now, to illustrate the importance and degree of transparency in cell therapy trials, I’d give you 2 examples:

1. Osiris NCT00366145 Phase 3 trial to assess efficacy of mesenchymal stem cells (product Prochymal) in GVHD.
Study was completed in May 2009. According company’s press release, the trial has failed. Since 2009 (3.5 years) neighter results were posted in database nor published in literature. A month ago, the first failure analysis has been published and publicly discussed. Since May 2009, more than hundred trials, involved mesenchymal stem cells infusions were initiated, including about 10 in GVHD.

If the results of this trial were published and posted in 2009, would it allow to circumvent potential errors in cell product preparation and trial design? YES! Why are we learning about the potential causes of this failure just now – 3.5 years later? Why? Why FDA mandate didn’t mean anything for the company? Why didn’t they get penalized for $10,000 (as per FDA law) per each day of delay in results posting?

2. NIH-sponsored NCT00684060 The Late TIME Phase 2 trial to assess bone marrow mononuclear cells after hear attack.
The study was initiated in 2008 and completed in February 2012. The study’s results were posted in database in April 2012 (2 months after completion) and published in 2010 and 2011. Cell preparation and process validation and study design were published in 2010and 2012. The trial has failed. Some failure analysis and discussions were posted here and here.

Based on rapidly posted and published results of the Late TIME we can learn a lot of issues and challenges and avoid them in design of future trials or even stop to pursue the same intervention. It allows to save a lot of time, money and efforts.

I’m not trying to say that industry is bad, but academia is good. I’m just picking 2 quite opposite examples of transparency. Some companies can be very transparent, at least at early stages.

So, the lack of transparency and publication/ reporting bias represent fundamental flaw of medical research in modern evidence-based medicine. It is unacceptable. It is a medical research fraud! How can we fix it? The fix is easy. If you’re professional – just do it! Always report and publish results timely and openly, irrespective of outcome! Think about patients and progression of the field! If you’re a regulator – enforce accurate registration of trials and results reporting. If you’re a patient – demand the full information as soon as possible. Right now, all of us can sign a petition to support registration and results reporting of all trials. The project AllTrials has been recently launched and, so far, got nearly 30, 000 signatures.

I hope cell therapy field will not have a lot of problems due to lack of transparency. I hope everyone in the field will realize how critical it is! It is vital for rapid progression of the field. It is vital for patients protection.

{ 3 comments… read them below or add one }

Amy Price February 11, 2013 at 10:20 am

Alexey, this is an excellent article. I incorporated it into the iThinkWell blog http://www.ithinkwell.org/stem-cell-science-and-gsk-urge-trials-reporting and suggested people read the entire article. I see results that should be reported both for safety and to save others from repeating mistakes and wasting time. Then the energy and genius is saved for solving real problems accurately, It would save money too as then there would be less duplication of resources. Thank you for being the first cell scientist to write this and you have done it with great clarity

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Alexey Bersenev February 11, 2013 at 10:32 pm

Thank you for your support Amy!

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Matt MIller April 23, 2015 at 6:26 pm

It is incredibly regrettable that the results of clinical trials aren’t always posted. I think that the truth behind this is that because money is often involved in the development of these new treatments, companies that conduct clinical trials would rather not publish data that could shed a negative light on their IND, but would instead like to conduct further research with different patient populations that produce more favorable results. As we have seen through asian bridging studies, efficacy of treatments as well as dosage will vary between patient populations of different ethnic backgrounds. Instead of admitting failure, I feel that these companies would rather re-evaluate their treatment, conduct further research, and wait to publish results that are more positive, so as to not discourage further research for something that could potentially work for more-specific patient populations.

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