Under-representation in Clinical Trials: Participants with rare diseases, reporting and awareness.

Introduction: Trial populations need to reflect those in the community who may benefit from the treatment being tested if the results of the trial are to maximise patient health gains.

The European Union defines a rare disease as one affecting fewer than 5 in 10,000 of the general population. With over 8,000 known rare diseases, almost 6% of the population will be affected by a rare disease. This equates to approximately 3.5 million people in the UK and 30 million people across Europe.

Consequently one would expect 6% of those recruited to clinical trials to have a rare disease; however this is at best unknown and likely to not be the case. This study will investigate the representation of rare disease participants within clinical trials and possible reasons for under-representation of these participants, including (i) lack of reporting that a participant has a rare disease, (ii) potential exclusion due to the recruitment criteria to the clinical trial and/or (iii) lack of awareness of rare diseases.

Methods: A sample of clinical trials for anti-hypertension medications, listed on ClinicalTrials.gov, will be investigated. Representation of participants will be considered by analysing the reporting of participants’ rare disease and the inclusion/exclusion criteria from protocols, reports and publications of the clinical trials. Awareness of rare diseases will be explored through a network analysis of the citation of rare disease literature using CitNetExplorer, specifically citation of the European Union definition of a rare disease.

Potential relevance and impact: The aim of the UK Strategy for Rare Disease is to ‘ensure no one gets left behind just because they have a rare disease’. Clinical trials are pivotal to the improvement of patient health, and require representation of all patients, including and inclusion of rare disease patients in clinical trials.