Frequently Asked Questions

Historically, the UK has played a prominent role in CF research. It has been traditionally strong in genetic aspects of research. In the 1990's, three groups working largely independently at Imperial College London, the University of Oxford and the University of Edinburgh had each undertaken genetics research that moved from laboratory to early pilot clinical studies of gene therapy. The studies were all promising, but limited in scale and outcome by the size of each group and the areas of specialist techniques available to each. To move the field forward in 2001, in partnership with the CF Trust, these three groups were brought together to form the UK CF Gene Therapy Consortium.

Collectively, the Consortium has a greater breadth of expertise than any one group. It works independently and thus has a much greater chance of bringing effective gene therapy to the clinic than ever before. With ~70 staff working together, the Consortium has the ability to undertake every step of the long and complex process necessary to research and develop improved methods for gene delivery, first in the laboratory, then in model systems to ensure that only the safest and most effective options are tested in patients. The team has a good balance of technicians, scientists, nurses, clinicians and administrators, all working together and overseen by a Strategy Group. The Strategy group has overall responsibility for the Consortium, to the CF Trust and to the patients.

Once we have made what we think is an important step forward in the design and optimisation of our gene therapy agents, we must follow a well described and tightly regulated process of regulatory review and manufacture of clinical grade reagents. In the UK, all medical research is subject to independent review and consent by Medical Research Ethics Committees; all proposed new medicines are subject to approval for clinical trial by the Medicines and Healthcare products Regulatory Agency; and additionally for gene products, by the Gene Therapy Advisory Committee. This is the most costly and time-consuming process between the research laboratory and the clinic. On forming the Consortium, our immediate priority was to perform a critical review of all of our previous work and pool all of our resources and 'know how'. Next, we embarked on researching and developing essential improvements to our gene therapy product so that it would last longer upon administration. In parallel, we evaluated all available delivery agents to assess which worked best with our redesigned product so that it could be delivered without damage through the nebuliser we would use in the clinic. This we call the Wave 1 product. We started moving our Wave 1 product through the regulatory process in May 2007. By September 2008 we had reached the stage when we had approval to test the product once each in a limited number of CF patients. These studies, completed in April 2011, are an essential part of the approval process to establish that the product is safe.

Developing a new drug treatment from new idea, through laboratory tests, regulatory approval, successful clinical trials and licensing the final formulation as a new form of treatment is always a long and costly process. Current estimates from biotechnology and pharmaceutical companies put this as between 12-14 years at a total cost of ~£400million, split more or less evenly between the stage we are currently at and the licensing of the product for clinical use. We have spent ~£20million to get from idea to successful Phase 1 safety studies. We will certainly need help from industry when larger scale studies (Phase III/IV) are needed. We have therefore reached our current stage in a similar time frame to industry, but at substantially lower cost.

Our research is being undertaken within three of the UK's leading medical research Universities (all three consistently ranked by the Times Higher Education in the top 50 worldwide). This provides an excellent laboratory and clinical research environment and associated infrastructure for the Consortium, in partnership with the National Health Service. But only a minority of the staff involved are employed directly by the Universities or the NHS. In keeping with medical research generally, the majority of the direct staff and research costs must be raised in the form of research grants, donations and other funders. Gene therapy is still a new area of research. We have a clear idea of all the stages that must be completed in the journey from scientific idea to clinical product. But, like any journey into new territory, there are potential pitfalls and time delays to be balanced against possible short-cuts. Thus, our work is proposed and reviewed in stages. We have set our course, passed all of the preliminary stages and have the primary goal of a multi-dose clinical trial in our sights. From 2002 to 2011, our main funder was the CF Trust through a succession of grants awarded. The Consortium submitted formal costed proposals which were subject to external peer review (see below) and regular oversight by the CF Trust's Gene Therapy Scientific Advisory Committee. Since the beginning of 2012 we have been funded by two UK Government agencies, the Medical Research Council and the National Insitute for Health Research.

External peer review is the name given by grant awarding bodies to the process used to reach decisions on which medical research to fund. Research proposals are submitted to the funding agency, who then send the proposal to independent experts in the field. These experts review and make recommendations, e.g. 'fund in full'; or 'fund this, but not that aspect of the proposal'; or 'reject'. The funding agency will usually have a second, internal group of experts who look at the external reviews and make their own collective recommendations whether to fund or not, and if so at what level. An award letter is then sent to the Universities, some or all of the existing staff may have their contracts renewed, new staff may need to be recruited to bring in additional or new expertise, and the work begins against the agreed research plan and the budget provided.

Grant submissions and awards are an important part of how we report our research progress. It is a key aspect of the external peer review process (see above). Since 2001, we have applied for and been awarded successive grants from the CF Trust, one grant from the Department of Health and one grant from a charitable foundation that wishes to remain anonymous. For the medical research community, progress is primarily assessed by the rate of publication of the research findings in scientific and medical journals. Since 2001, we have published over 100 research papers and scientific reviews. Progress can also be measured by evaluating the number of talks and posters presented at national and international scientific meetings. Since 2001, we have presented more than 200 research talks and posters. We also reported formally to the CF Trust via the CF Trust's Gene Therapy Scientific Advisory Committee. Since 2001, we made 9 formal reports consisting of extensive written and verbal presentations of scientific achievements by the Consortium Strategy Group, typically spread over 2 days, which was then critically debated by the CF Trust's Gene Therapy Scientific Advisory Committee. We regularly present research updates to lay groups and the CF community, including special features in the CF Newsletter as well as the mainstream press and television.