European clinical research
Where are we, where should we go?

U. Smith, Vice-President EASD

The epidemic of diabetes – especially type 2 diabetes - remains largely unchecked. Although clinical research is addressing some of the issues, many large-scale trials are failing to improve clinical decisions or stem the tide of complications. The EASD is concerned about the limited range of clinical trials and studies, their relevance and their funding.

Lack of diabetes clinical research is a crisis in Europe
Despite substantial investment in diabetes research across Europe, many questions remain unanswered. We face a crisis in funding. Almost any worthwhile clinical study over three years will cost more than € 300,000, and large prospective studies many million Euros. Studies originating in universities may struggle to find funding from charities and non-governmental organizations (NGOs), and although pharmaceutical companies have invested heavily into large-scale trials, the focus of these trials can be limited. We need large-scale trials to address some of the most basic therapeutic options, especially related to the use of polypharmacy. Clinical research also needs funding for small-scale mechanistic studies, which establish the basis of the disease and investigations, which test new approaches to the onset, progression and complications of diabetes. In addition, we need to be encouraging young clinical scientists to work in these areas and ensure that their career progression is safeguarded. Nevertheless there is also some good news. The UK government is investing in a Diabetes Research Network, and in early phase trials through the National Institute of Health Research (NIHR). The EFSD has allocated significant tranches of money to clinical aspects of diabetes as well as supporting basic research. But Europe-wide we need to be aware that lack of funding will stifle progress and degrade the position of European science and medical practice.

Diabetes clinical research stifled by regulation in Europe
Regulation is essential to bring safe, efficacious drugs to market. In a world concerned about drug safety, the pressure is on the regulators (the FDA in the United States and the EMEA in Europe) to be particularly cautious. But every new regulation and demand lengthens the time between discovery and clinical use. The bureaucracy imposes many months of process. One needs to add to this the time for ethics review, time for adoption in the case of networked trials, the processes associated with national clinical excellence or cost effectiveness statements, and the local vagaries of pharmacy committees. All this extra time is very costly. Such regulatory hurdles may mean that trials and research are controlled more and more by the pharmaceutical industry and one or two NGOs. Yet the science base for innovation and for the appropriate use of medicines depends on harnessing the academic power of research centres and engaging healthcare professionals in the process of enquiry into fundamental science and the cost-effective use of therapeutic regimens.

Pharmaceutical companies are designing self-interest trials
Pharmaceutical trials tend to design studies, e.g. in response to questions raised by regulators, that minimize risk for negative outcomes and maximise the target patient-base. Although such studies will enhance our understanding of the use of pharmaceutical interventions, they also leave vital and fundamental questions unanswered. For example, a drug trial may demonstrate the efficacy of an agent without showing whether or not it is better than a cheaper and available alternative. Comparator trials may be set up where the pharmaceutical agent is shown in the best possible light, with the widest indication for use. This may skew prescribing habits across Europe. Combination therapies may improve compliance but may not be compared in a trial setting with similar costing monotherapies.

New opportunities for patients to advance diabetes research
With increasing media coverage of research, there are new avenues to engage the public in decisions about ways in which research should be carried out and increased opportunities for patients to participate in clinical research trials. Many patients find this rewarding as it brings them into close contact with healthcare professionals working on the trial. Evidence suggests that most view trial participation as an educational experience in its own right.
The diabetes community should be clearer in its message about rights and responsibilities. Patients have rights to safe, efficacious medications and good clinical care, and often receive reimbursement of new expensive drugs. From the latter point of view it may not be unreasonable to expect from patients that they participate in systematically conducted post-authorisation studies in order to determine whether newer drugs are really an improvement and whether they represent good value for money.

Diabetes treatment options should be tailored to individuals
Diabetes is a complex disease with many facets that may need specific treatment. Type 2 diabetes is often characterised by high blood pressure, high blood fats, obesity and by heart disease. In any given individual these aspects will require tailored therapies to control them. It is certain that clinical research directed at discovering which groups of patients will respond best to different agents would be of vital importance. Yet little research is directed at identifying the optimal treatment for an individual – partly because of market forces. Clinicians report regularly that drugs will work on some patients, but not others. Nor is this simply a matter of compliance. One class of drugs may have little effect and another cause a dramatic improvement. The reasons are wide-ranging, and include genetic, racial, cultural, social and environmental factors. Governments running health services should be concerned not only with total costs and overall indications, but also with best tailored outcomes. Who responds to what is a vital question – and we need more answers.