Scientist - News - 17-12-2009:
Inspectorate publishes evaluation of controversial probiotics trial
The Netherlands Health Care Inspectorate (IGZ) has released its evaluation report on the probiotics trial conducted at the University Medical Centre (UMC) in Utrecht. This trial was characterised by an unexpectedly high mortality rate among patients with acute pancreatitis in the experimental group. The report conclude that several organisational mistakes have been made. However, it does not conclude that the deaths can be attributed to these shortcomings.
The UMC Utrecht trial aimed to test whether patients with acute pancreatitis may benefit from probiotics. This was expected to be the case, given the positive effect of probiotics on the immune system. However, 24 of the 152 patients in the probiotics group died, versus 9 out of the 144 control patients. This difference was statistically significant.
The IGZ-report does not address a potential underlying cause of this extra mortality. It only addresses the procedures that were followed. The IGZ conducted its evaluation in collaboration with the Dutch Food and Consumer Product Safety Authority and the Dutch Central Committee on Research involving Human Subjects.
One of the main conclusions is that the party that commissioned the research, UMC Utrecht, did not comply with all legal obligations for medical-scientific research. The report does not identify a causal relationship with the extra mortality. It does state, however, that the relevant medical-ethical evaluation committee should have been more critical in its substantive evaluation of the research proposal.
In addition, the committee responsible for the study’s safety aspects has not always been informed on new developments – such as deaths – in a timely and correct manner. This committee should have had clearer instructions and procedures, concludes the IGZ, in which case it could have played a crucial and active role. For instance, it would have been preferable for the two groups not to have been blinded during the interim analysis, “in order for all possible scenarios to be clearly assessed”.
According to the IGZ, UMC Utrecht and the senior executive researcher had insufficient clinical knowledge of the probiotics in question. Moreover, it was not exactly clear which probiotic strains were involved. At the start of the study, there was insufficient scientific information about the application of this research product in humans.
The report concludes with a number of practical recommendations directed at the various stakeholders: the Ministry of Health, UMC Utrecht, the producer of the probiotics, and the medical-ethical evaluation commission. The main recommendation for UMC Utrecht – and thus, stresses the IGZ, for all institutions that commission similar research – is that the party commissioning the research should “provide an adequate research infrastructure to conduct clinical research, in which the tasks and responsibilities of the commissioning party and the researcher are clear and in accordance with national law.” The report recommends that the Ministry ensure that national law for such clinical research no longer distinguishes between products that are tested as medicines, and those that are not.
In an official reaction on its website, UMC Utrecht states that it deplores the shortcomings that were identified. It “notes, however, that these mainly concern procedural aspects, rather than patient care. UMC Utrecht will further scrutinise the lessons learnt, as it has done in the past two years, and will ensure they are practically applied where possible.”
More information (all in Dutch):
The IGZ evaluation report
IGZ press release
UMC Utrecht’s official reaction
Article in het Financieele Dagblad (December 16th):