Most clinical trials led by German universities violate medical ethics and many waste taxpayer funds, a comprehensive study of 1,509 trials shows
75% of trials were not prospectively registered
433 clinical trials have become research waste due to non-publication
These unpublished trials aimed to recruit 56,730 patients
Update: This blog was written based on a preprint. The final paper, published in June 2019, can be found here.
Failure to prospectively register trials or publish their results are both clear breaches of global medical research ethics. In addition, clinical trials whose outcomes remain unpublished are a waste of precious medical research funds because they contribute nothing to medical progress.
The table below shows how the 21 German universities who led the most clinical trials perform on research waste. The university of Düsseldorf performs best: ‘only’ 15% of its trials have become research waste, while the remaining 85% of its trials have reported results. The worst university is Aachen, which has left 47% of its trial results completely unpublished.
The study team has created an interactive data visualization tool which allows users to explore the performance of all 36 universities covered in detail.
The best performers in terms of research waste countrywide are Rostock (8%), Regensburg and Homburg (both 9%). The university of Lübeck performs worst; 53% of its clinical trials are research waste. These universities are not included in the table above because they have led a smaller number of trials.
In terms of breaching patient trust, the university of Heidelberg performs worst. It set out to recruit 14,688 patients into trials that remain unpublished. Berlin (5,821 patients) and TU München (5,248 patients) come second and third last on this metric.
The data set, which covers 36 universities, shows that even those trials whose results were published usually fell far short of WHO best practices.
German universities posted the results of only 13 out of 1,509 trials (less than 0.1%) onto a trial registry within 12 months as recommended by the WHO. In a further breach of global best practices, the results of only 39% of trials had been published in any form – on a registry or in an academic journal – within 24 months of trial completion.
Such long time lags between discovery and publication slow down medical progress, meaning that patients have to wait longer for new treatments, vaccines and cures to be developed.
Data collected in early 2017 suggests that German funding agencies could do more to prevent research waste among their grantees. The top two German public trial funders (Deutsche Forschungsgemeinschaft and the Federal Ministry for Education and Research) have yet to sign up to the WHO Joint Statement and commit themselves to global best practices in curbing research waste.
Earlier this year, IQWIG, the German agency responsible for assessing the efficacy of medical treatments, proposed imposing sanctions on German universities that fail to share clinical trial data.
Similar measures are being debated in the United States, where a trial transparency law incorporating steep fines is already in force. In the UK, parliament has recently called for ‘tough sanctions’ on universities and other trial sponsors that fail to prospectively register clinical trials and report their results; the government in London is expected to respond before the end of the year.
Till Bruckner, founder of TranspariMED, said:
“These new figures paint a shocking picture of German universities' disregard for ethical imperatives and global best practices. Much of the research conducted at German universities is financed by public money. German taxpayers should not have to pay for medical research that is unethical, and German patients should not be expected to participate in clinical trials that make no contribution to scientific progress. Excellence in registering and reporting research is an integral part of overall research excellence. The universities of Rostock, Regensburg and Homburg show that German academic institutions can and should be expected to do far better than this.”
According to the Declaration of Helsinki, which governs medical research in human participants,
“Every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject… Researchers have a duty to make publicly available the results of their research on human subjects and are accountable for the completeness and accuracy of their reports.”
According to WHO best practices, all trials have to post their summary results onto trial registries within 12 months of their primary completion date, and publish their results in an academic journal within 24 months.
The study discussed above was produced by a team centred around the Berlin Institute for Health's QUEST Center for Transforming Biomedical Research, an academic center that "strives to increase the value of biomedical research". The QUEST team reviewed all trials by the 36 German university medical centers that were officially completed between 2009 and 2013, and that had been registered on Clinicaltrials.gov and/or the German trial registry DRKS. It did not take into account EudraCT registry data. The search for trial outcomes published in academic journals was performed manually, following a multi-step search protocol.
Note: This report by Transparency International et al summarizes the legal and ethical rules, and global best practices, applicable to clinical trials. This report by Universities Allied for Essential Medicines and TranspariMED explains why universities should be expected to post all clinical trial results onto public registries within 12 months, in addition to publishing their outcomes in academic journals. This case study provides useful guidance to universities that want to improve their performance.