Be open about drug failures to speed up research

It can take 20 years or more to get a drug to market, from testing compounds in animals to running late-stage (phase III) clinical trials in thousands of subjects. More than 80% of drugs that are tested in humans fail to demonstrate safety and efficacy1 (see ‘High failure rate’); the rate for Alzheimer’s treatments is estimated at more than 99%2 (see ‘Alzheimer’s drug attrition’).

Yet the data behind these failures are generally not seen by regulators, or considered deeply by anyone outside the company sponsoring the trial. Without this information, learning is unlikely….

Initiatives for private companies to share biomedical data and ideas have expanded in the past decade. Some, such as the Biomarkers Consortium and the Structural Genomics Consortium, bring together many companies and academics to design experiments for the benefit of the community, such as identifying disease markers or characterizing tool compounds to understand how target proteins work. Others ask companies and academic groups to pool data in a common repository. For instance, the Project Data Sphere Initiative is a platform to share de-identified data from people who were enrolled in the control, placebo or even experimental arms of more than 180 cancer trials….

Information that is not shared is arguably the most important: data that failed to meet drug developers’ hopes are most likely to help progress. Large clinical trials are multimillion-dollar experiments to validate a hypothesis that an experimental drug will be effective and safe. Results that go against these expectations must be made available to refine hypotheses and to elaborate alternative ones.

Data from negative research can reveal whether a trial adequately tested the intended hypothesis. …”

FDA fails to collect over one billion dollars in fines from law-breaking pharma companies and universities | transparimed

“The FDA Amendments Act was originally introduced to prevent companies from burying research results that show their drugs to be harmful or ineffective. Negative publicity around past disasters linked to hidden clinical trials seems to have pushed pharma companies into compliance. Today, the leading drug companies publish their trial results as required by law nearly all of the time, though some of the less prominent commercial trial sponsors continue to do badly.

In contrast, even some of the major universities and nonprofits perform dismally….

If the FDA was enforcing the law, New York University School of Medicine alone would be facing a $7,647,109 fine for its illegal and unethical behaviour. However, to date, the FDA has not collected a single cent in fines….

The FDA has recently signalled that it may in future start selectively imposing fines on some occasions. Transparency advocates have sharply criticized the FDA’s plan for lacking teeth. …”

Crackdown on unreported trials is good news for researchers

On 30 October, the House of Commons Science and Technology Committee issued its long-expected report on clinical trials transparency. The report notes that even today, around half of all clinical trials in the UK still fail to post their results onto registries.

As official documents go, the report is remarkably candid—the word “disappointed” leaps off the pages again and again. The parliamentarians’ ire may have been heightened by the fact that five years earlier, a similar report from the same committee called for decisive government action, evidently to little effect.

The latest report singles out universities and NHS trusts for particular criticism, citing data from the recently launched EU Clinical Trials Tracker, an online transparency tool. The tracker paints an unflattering picture of academic institutions’ performance. Across Europe, only 11 per cent of university-sponsored trials have posted their results. In contrast, many pharmaceutical companies boast reporting rates of close to 100 per cent….

Most universities, however, seem to have missed the boat. In July, the London School of Hygiene and Tropical Medicine was forced to admit that it did not even know how many trials it had sponsored, let alone how many had reported their results.

While institutional inertia seems to have been the main culprit, widespread ignorance of disclosure rules also played a role. Many universities were not aware that each and every clinical trial has to post its results within 12 months of completion, regardless of whether its outcomes have been published in a journal….”

EU Trials Tracker — Who’s not sharing clinical trial results?

“Non-reporting of clinical trial results is an ongoing global public health problem.

The best currently available evidence shows that around half of all trials go unreported: this means that doctors and patients see only a partial, biased fraction of the true evidence. We cannot make informed decisions about treatments unless all the data is reported. Under EU rules, from December 2016, all trials on the European Union Clinical Trials Register (EUCTR) should post results within 12 months of completion. There has never been a rule as simple and clear as this, anywhere in the world. Our EU Trials Tracker shows which organisations are compliant, and which aren’t. Our paper in the BMJ analysed the data as of January 2018, and found that only 49% of Europe’s clinical trials reported results in the register….”

Project Data Sphere

Project Data Sphere, LLC (PDS), an independent, not-for-profit initiative of the CEO Roundtable on Cancer’s Life Sciences Consortium (LSC), operates the Project Data Sphere platform, a free digital library-laboratory that provides one place where the research community can broadly share, integrate and analyze historical, patient-level data from academic and industry phase III cancer clinical trials.

The Project Data Sphere platform is available to researchers affiliated with life science companies, hospitals and institutions, as well as independent researchers. Anyone interested in cancer research can apply to become an authorized user….”

A DREAM Challenge to Build Prediction Models for Short-Term Discontinuation of Docetaxel in Metastatic Castration-Resistant Prostate Cancer | JCO Clinical Cancer Informatics

“We designed an open-data, crowd-sourced DREAM Challenge for developing models with which to predict early discontinuation of docetaxel treatment. Clinical features for all four trials and outcomes for three of the four trials were made publicly available, with the outcomes of the fourth trial held back for unbiased model evaluation. Challenge participants from around the world trained models and submitted their predictions. Area under the precision-recall curve was the primary metric used for performance assessment….

This work represents a successful collaboration between 34 international teams that leveraged open clinical trial data. Our results demonstrate that routinely collected clinical features can be used to identify patients with mCRPC who are likely to discontinue treatment because of adverse events and establishes a robust benchmark with implications for clinical trial design….”

Open Source 3D Printing: Exploring Scientific and Medical Solutions

“Open Source 3D Printing eliminates all the issues we just discussed in the proprietary section. Not only does it reduce costs, it enables easier innovation to solve issues faced during 3D manufacturing….

It is now possible for users to completely go Open Source, making it possible to greatly reducing production time and manufacturing costs!…

[I]n this final and most important section, let us pick related applications that we just discussed and look into some examples in detail where we feel Open Source Approach is most necessary…

An Open System that enables such customized Printing of bio-materials that diverse in nature will make it much easier to conduct research in Tissue Engineering….

Finally, we focused on the Scientific and Medical Solutions for Open Source Bioprinting by looking into initiatives for saving our corals, teeth replacement with anti-bacterial abilities, Bioprinting with focus on Open Source Bioprinting and Applied Nanotechnology for Organ Transplant. In our final subsection, we also highlighted the role of 3D Printing in Drug Discovery.

These are only some of the many applications of 3D Printing. We believe there is a need for Proprietary manufacturers to migrate towards Open Source Business Models that would promote better applicability for our planet.”

The 5:AM Altmetric conference took place from 25th-28th September 2018 at the London School of Advanced Study – Leeds University Library Blog

The School of Advanced Study is in Senate House or, if you’ve seen the film of George Orwell’s 1984 starring John Hurt, the Ministry of Truth, fitting perhaps for a conference considering the modern information environment where science communication vies online with “fake news”.

What Is “Open Science?” Why the Future of Psychedelic Science Depends on It | Inverse

“There is a growing research literature suggesting psychedelics hold incredible promise for treating mental health ailments ranging from depression and anxiety to PTSD. But how do we know for sure?

The way forward for psychedelics is through “open science.” Researchers should pre-register their plans and share their data, as we have in our own research….”

Compliance with requirement to report results on the EU Clinical Trials Register: cohort study and web resource | The BMJ

Abstract:  To ascertain compliance rates with the European Commission’s requirement that all trials on the EU Clinical Trials Register (EUCTR) post results to the registry within 12 months of completion (final compliance date 21 December 2016); to identify features associated with non-compliance; to rank sponsors by compliance; and to build a tool for live ongoing audit of compliance….

Results Of 7274 trials where results were due, 49.5% (95% confidence interval 48.4% to 50.7%) reported results. Trials with a commercial sponsor were substantially more likely to post results than those with a non-commercial sponsor (68.1% v 11.0%, adjusted odds ratio 23.2, 95% confidence interval 19.2 to 28.2); as were trials by a sponsor who conducted a large number of trials (77.9% v 18.4%, adjusted odds ratio 18.4, 15.3 to 22.1). More recent trials were more likely to report results (per year odds ratio 1.05, 95% confidence interval 1.03 to 1.07). Extensive evidence was found of errors, omissions, and contradictory entries in EUCTR data that prevented ascertainment of compliance for some trials.

Conclusions Compliance with the European Commission requirement for all trials to post results on to the EUCTR within 12 months of completion has been poor, with half of all trials non-compliant. EU registry data commonly contain inconsistencies that might prevent even regulators assessing compliance. Accessible and timely information on the compliance status of each individual trial and sponsor may help to improve reporting rates.