By Emma Batten, Research Assistant, DEBRA UK

Published: 11 January 2019

DEBRA UK is a medical research charity, (now one of 50+ DEBRAs around the world), which continues to fund much needed pre-clinical and early stage clinical research into the devastating and painful genetic skin blistering condition, Epidermolysis Bullosa (EB). This basic research is an essential starting point in the drug development process to understanding EB at the molecular and cellular level that has now led to DEBRA funding projects around the world.

In a rare disease such as EB, cellular and molecular therapies require complex safety testing and tailoring to particular types of EB and individual patients. This also creates additional cost and time to the clinical research programme, in order to generate sufficient data [1] required to carry on to the next phase.

The challenges

As small populations exist in the field of rare diseases, there is inevitably a limited amount of data about the disease and understanding the natural course and impact. In many cases, there may be little background research that helps to support clinical trial design and planning. This is certainly the case for clinical trials in EB as populations tend to be heterogeneous with many genotypes and phenotypes, and outcome measures can be difficult to define.

Even though the principal challenge in rare disease drug development is the small number of patients, once patients are identified for a clinical trial, it can be difficult for them to participate as there can be a limited number of trial sites and there are always medical inclusion and exclusion criteria to consider. There are also additional tests and the challenges of travel that need to be considered with complex medical problems.

Here are some examples of the challenges that some of our DEBRA UK funded researchers have faced when recruiting patients to participate in a clinical trial for EB. It is reported however, that many patients can be highly motivated and altruistic despite these challenges[2]:

  • Time – Committing to a trial when patients already have work, study or social commitments along with the large amount of time taken in their daily routine for dressing changes and standard clinic appointments.
  • Competing ongoing trials – Trials that may run in parallel with similar eligibility criteria. One trial may be chosen over another due to the possibility of a direct benefit, such as wound healing as opposed to taking part in a trial that may only be testing for safety, such as a Phase I gene therapy trial.
  • Exclusion criteria – The study’s exclusion criteria may limit recruitment in an already limited population. With rare diseases, if participants are too few, there must be consideration between having less restrictive criteria or producing results with more statistical power.
  • Travel and cost - It can be difficult for EB patients to not only have the burden of travel, but also possibly pay for travel and accommodation for themselves and carer’s accommodation if trial sites are far from home.
  • Additional clinical tests – these can include blood tests and biopsies, therefore fear of needles or scarring from biopsy sites, on top of routine medical care may affect recruitment.
  • Family commitments/ bereavements
  • Misconception about cell and gene therapies – discussion between patients that these may proliferate misunderstandings

Tips for overcoming some of these challenges:

  • Include patients in the clinical trial design from the start.
  • Carefully consider flexibility of eligibility criteria[3] and ensure it is justified.
  • Try and open some ‘shared care’ sites such as GP practices or hospitals or meet patients at their home.
  • Help patients’ book travel and hotels where possible and pay upfront from a study account.
  • Have early, late or weekend appointments available where possible to fit around patients’ schedules.

Working internationally

DEBRA has made a substantial drive to advance clinical research globally in EB. As well as funding early phase clinical trials, DEBRA UK continues to fund a project on the natural history and progression of EB at Guy’s and St.Thomas’ to gather data on the natural course of EB and clinical end points to help improve clinical trial design[4].

It is also important that we work with our international research partners such as other patient organisations, biotech and pharmaceutical companies, as this helps to continue to increase awareness about EB. In doing so, more ideas are shared with protocols, connecting research sites, improving recruitment and working together to overcome the logistical challenges that rare disease patients face when joining a clinical trial[5]. DEBRA UK with other partners will be holding an EB global congress in January 2020 as another step to address some of these challenges.


[1] Trounson and McDonald, 2015

[2] DUK Researchers, St. John’s Institute and Guy's and St Thomas', 2019

[3] Sarajian, 2018

[4] Augustine, Adams and Mink, 2013

[5] Amengual et al., 2018