Peter Grabitz really wanted to help his uncle. Helping people, helping them in difficult moments, giving the sick the best possible treatment – why else was he studying medicine? In 2018, Grabitz naturally also stood by his uncle Michael Zehnbauer when the 53-year-old received bad news from his doctors: Zehnbauer had been suffering from bile duct cancer for half a year, a disease that you can live with on average for another two years Has. Now the doctors only gave him a few more weeks. They had tried everything, for them the patient was out of therapy.
They only opened up a tiny possibility for him: Michael Zehnbauer’s cancer had a special mutation. Indeed, there was a drug called enasidenib that was developed by the Celgene company for precisely such tumors. However, it only had an approval for blood cancer. The drug was also examined in a study on patients with solid tumors, including bile duct cancer. For Michael Zehnbauer that was a glimmer of hope. It was even more than that. It was his last hope.
But nowhere was it to be found how the patients with enasidenib had fared. Although the study ended in 2016, Peter Grabitz did not find its results in any database. For this reason, his uncle’s application to his health insurance company to take over the treatment with enasidenib also failed. Without proof that the monthly 30,000 euro therapy offers a chance of success, this would not be possible, wrote the health insurance fund. Shortly afterwards, on February 15, 2019, Michael Zehnbauer passed away.
“It would have been much better for him to find out about the outcome of the study.”
After his death it became clear that the drug would probably not have helped him, the study had turned out badly, and the drug was apparently of no use for solid tumors. Peter Grabitz finds it all the worse that his uncle in Bavaria was hoping for the drug in the last weeks of his life and was so desperate when he did not get it. “He really clung to it, thought there was still one chance,” says the 28-year-old doctor who now works for the World Health Organization and also deals scientifically with transparency in research. “It would have been much better for him to know about the outcome of the study.”
And what’s more: it would have been Zehnbauer’s right too. Pharmaceutical companies and other researchers are obliged to register all clinical studies with patients in the EU database EudraCT and to enter the results no later than one year after the end of the study. This also applies expressly to negative results. After all, patients and doctors also benefit when they find out that something is not working. But the Celgene company simply let the negative result disappear into a drawer – just like many other researchers. A Evaluation by Oxford University and the non-governmental organization Transparimed, which was available to NDR, WDR and SZ before publication, shows how often this happens.
The authors discovered a total of 5976 studies in 14 European countries that were approved in 2015 or earlier and the results of which have not yet been published. The largest gaps are found in Italy (1221 studies without published results), Spain (884), the Netherlands (839) and France (698). This is followed by Germany with 554 studies. After all, that’s 56 percent of all studies for which one can expect results. “The national authorities failed to demand the publication of the study results,” says Transparimed founder Till Bruckner, whose organization has been campaigning for more transparency in medicine for years and has repeatedly pointed out the problem of unpublished studies.
Not only pharmaceutical companies but also universities often do not publish their results, even though their work was even financed with public money. Even the outcome of studies with children, who are ethically particularly difficult, often remains hidden from the public.
Why did Celgene not publish its enasidenib data? Upon request, the pharmaceutical company Bristol Myers Squibb, which bought Celgene in 2019, announced that it did not find out until 2021 that “the results of this study were inadvertently not published”. Thereupon one “took the appropriate steps to disclose”. The study has now actually been published.
The regulators do little. They have no handle, it is said.
However, the supervisory authorities in many European countries are doing little to ensure that researchers better fulfill their obligations in the future. In Germany, the Paul Ehrlich Institute (PEI) and the Federal Institute for Drugs and Medical Devices (BfArM) are responsible for this. The PEI did not respond to a request from NDR, WDR and SZ about the allegations. The BfArM, on the other hand, replied that it had “no legal sanctioning powers” against those responsible for studies if they did not publish the results in the EU database.
At the beginning of May, various organizations, including Transparimed, Cochrane and Transparency International, appealed to BfArM President Karl Broich to work to improve transparency. Broich then, in consultation with the heads of authorities in other EU countries, asked the EU to emphasize the publication obligations by “creating legal regulations”, as a BfArM spokesman announced. There was no doubt about the importance of the topic, he said, after all, “unpublished studies with unfavorable results can have negative effects on public health”.
Michael Zehnbauer died of bile duct cancer in 2019. In the last few weeks of his life he had hoped for a new drug, but the pharmaceutical company did not publish the study results.
(Photo: private)
Great Britain, of all countries, which has left the EU, shows that there is another way. According to the analysis by Transparimed, there is not a single national study that was registered until 2015 and the results of which have not yet been published. In Germany, on the other hand, seven percent of all studies were not even registered in the database. Hiding studies not only harms patients, says Bruckner, it is also a waste of research funds because the exact same study may be carried out in different locations without the researchers knowing about each other.
Study transparency must be taken much more seriously by supervisory authorities across Europe, says Peter Grabitz. But something else is important: that there is increasing awareness among researchers from industry and universities of the importance of publishing even disappointing data. “With a supposedly negative study you can no longer scientifically win a flower pot,” says Grabitz. “Researchers would therefore prefer to invest their energy in other things. But science and its sponsors must realize how important the findings are for doctors and patients. They would have saved my uncle a lot of suffering in the last few weeks of his life.”