"There is an extensive list of requirements and some of them are interesting and show that the EMEA has analysed the issue in a broad way, however, there is absolutely nothing about patient informed consent," Professor Stephen Senn, from Glasgow University's Department of Statistics, told Outsourcing-Pharma.com. Prof. Senn made his skeptical comments in response to the pan-European drug regulator's draft guideline released this week which aims at preventing a repeat of last year's TGN1412 drug trial disaster in London. Senn chaired a working party of the UK's Royal Statistical Society (RSS) which published a report earlier this month calling for reforms in first-in-man clinical trials. The proposals for reform set by the RSS were aimed at minimising drug trial risk, maximising design efficiency and improving protocol review. 21 recommendations for improvement were made in the RSS report surrounding three key areas: risk assessment and communication; preparatory pre-clinical work; and experimental design, with particular attention to dosing. According to Senn, the EMEA's response is sound and interesting but there is a major lack of guidance in terms of the information given to patients who volunteer to participate in clinical trials. The guideline focuses on potential high-risk medicinal products - drugs where the mode of action, the nature of the target in the body or the limited relevance of animal models for the prediction of toxicological effects in humans raises concerns of serious adverse reactions during first-in-man clinical trials. Such drugs include monoclonal antibodies (mAb) which were at the centre of the TGN1412 debacle. The document gives guidance on handling the transition from non-clinical studies, such as animal or in vitro studies, to first tests in humans for such "high-risk" types of drugs. The committee's proposals also cover quality, non-clinical and clinical aspects, including the calculation for the first doses to be given to human subjects, the initial dose-escalation trials and the management of risk - all of which Senn strongly supported. Nonetheless, "the EMEA are covering themselves," said Senn. "There is nothing in the draft guideline that helps healthy patients get the right information before getting involved in a clinical trial." "For each first-in-man trial, there should be a document that states what the risks are, what studies have been done before, and this document should be available to physicians running clinical trials and insurers, but most importantly to healthy volunteers." At the origin of the scrutiny on informed consent were the events that surrounded a Phase I trial of TGN1412, a mAb that was being developed to treat chronic inflammatory diseases and leukaemia. Six out of eight men involved in the trial experienced a severe and systemic adverse reaction and were admitted to intensive care with hours of taking the experimental drug. Those that were unaffected had been given placebo. "The big issue ethically is that those patients claimed they didn't know about the risks involved in participating in the trial," explained Senn. But, according to Senn, this issue of informed consent has not been addressed in any way in the EMEA's guideline, stressing that giving the right information to trials' volunteers is down to the regulator. What is more, many issues of clinical trial design have a statistical aspect, ranging from how pre-clinical studies should be translated into recommendations for starting doses in humans, to how many subjects to recruit and what dose schedules to use and including, of course, how results should be analysed. And yet the EMEA as well as many state members don't have statisticians employed by their respective drug regulator, which means they don't have the capacity to gather and analyse risk assessment data. "How can individual countries know how to apply this guideline if they don't have the resources? It is the EMEA's role to give the risk assessment of a drug before it can be tested on humans," said Senn. "It is very unclear how those conducting first-in-man clinical trials will efficiently make use of this proposed guidance so a disaster such as the one in London doesn't happen again."