The European Medicines Agency says it is open to discussing the use of complementary evidence sources and methodologies with developers of potential treatments for rare cancers, for which large-scale clinical trials are frequently impossible.

The Agency also has the approval mechanisms “to recognise uncertainties that are inherent to trials with small sample sizes in our decision-making,” says Robert Hemmings, chair of the EMA Scientific Advice Working Party. He was addressing a meeting with representatives of Rare Cancers Europe (RCE), held to discuss a new RCE consensus paper which is calling for innovative approaches to be used in collecting and summarising evidence for potential new treatments for such conditions.

A higher degree of uncertainty needs to be accepted for regulatory as well as clinically-informed decision-making in rare cancers, to overcome the limitations imposed by small-population trials, says the paper.

Patients with rare cancers should be allowed earlier access to promising experimental drugs, and rules need to be “relaxed” to consider the use of compassionate and off-label use of new drugs. Patients’ attitudes towards risk should be taken into consideration, and regulatory agencies and local health systems must allow a higher-than-usual degree of uncertainty, in order to avoid discriminating against rare-cancer patients, it adds.

“Medical decisions are usually risk-averse, for many reasons, but rare-cancer patients often argue in favour of relaxing rules so that new treatments can be tried,” said Kathy Oliver, founding co-director of the International Brain Tumour Alliance (IBTA).

As large trials are not feasible in rare cancers, initiatives such as low-power randomised clinical trials and adaptive trials should be considered, says RCE. Research on biomarkers should be inherent to research into new drugs, and the availability of electronic patient records, which allow the effectiveness of treatments to be measured through patient-reported outcomes in real-world conditions, is “a great opportunity,” it adds.

The report also suggests that surrogate end-points could replace clinical end-points, especially when available evidence needs to be brought to the patient’s bedside, to compensate for its possible limitations. New treatments could be used temporarily, under the assumption that the surrogate end-point is valid, while waiting for final results, it proposes.

Also, patients should be able to access information about ongoing trials easily and be encouraged to participate in them, says RCE. While data protection is important, patients should have the right to donate their clinical data and tissues for research and to give a one-time (withdrawable) enduring consent for their use. Europe needs feference networks involving centres for excellence and more cancer registries, it adds.

Francesco Pignatti, head of oncology evaluation at EMA, told the meeting that while most requests for scientific advice from the Agency come from industry, it  welcomes and encourages requests from academia for scientific advice for academic trials.  He also pledged the Agency’s willingness to continue working with RCE and the European Society for Medical Oncology (ESMO) “to understand exactly where research on rare cancers is struggling so that we can find a way forward.”