Clinical trials in diabetes are geared heavily to treatment rather than prevention, while they may omit population groups that could benefit substantially from better disease management, researchers from Duke University Medical Center and Duke Clinical Research Institute in the US have found.
In a study published in the journal Diabetologia, the researchers looked at diabetes-related trials registered with the US-based ClinicalTrials.gov database between 2007 and 2010.
This produced a subset of 2,484 interventional trials with disease-condition terms relevant to diabetes, which were further analysed according to parameters such as study goals, size and length of trial, primary outcomes, age of participants and global distribution.
Of the diabetes-related trials analysed, 74.8% had a primarily therapeutic purpose while 10% were preventive. The majority (63.1%) of the listed interventions involved drugs, with behavioural interventions accounting for 11.7% of all studies.
Need for prevention
The International Diabetes Federation (IDF) and the American Diabetes Association (ADA) “emphasise diabetes prevention as a focus of future research”, while previous trials have demonstrated that various lifestyle and pharmacological interventions may delay the onset of diabetes in high-risk subjects, the researchers pointed out.
Although “the ideal proportion of trials focused on prevention has not been established, the current trials portfolio, comprising studies with smaller sample sizes and shorter durations, appears to be inadequate for expanding and refining preventive efforts or translating effective care strategies into the community setting”, they commented.
Most of the diabetes trials analysed were designed to enrol 500 or fewer participants (91.1%), with 58.6% targeting enrolment of 100 or fewer subjects. Mean/median times to completion were 1.8/1.4 years respectively.
Only small percentages of the trials targeted people aged 18 years and under (3.7%) or 65 years and over (0.6%), while 30.8% excluded patients over 65 years of age and the majority excluded people aged over 75.
While people aged 40–59 years make up the largest proportion of those affected by diabetes worldwide, older people are at most risk from the disease, the researchers observed. For example, 26.9% of US residents aged 65 years and over were estimated to have diabetes in 2010.
Going by the exclusion rates seen in the analysis, the “current clinical research portfolio may not allow us to robustly address issues in older persons with diabetes”, the Duke University researchers suggested.
Type 1 growth
The low level of children and adolescents targeted for enrolment in diabetes trials “may be appropriate given the number of children affected by diabetes”, they acknowledged. However, the estimated 3% annual increase in the incidence of type 1 diabetes “may warrant greater representation”.
Moreover, the growth in type 2 diabetes among adolescents, “particularly noticeable in wealthier nations, is of considerable concern”. And it is unclear whether findings obtained from adults with diabetes are readily translatable to paediatric/adolescent populations, the researchers added.
Diabetes care organisations worldwide have also emphasised the need to minimise diabetes-related complications, they noted.
Groups such as the ADA have “strategically prioritised investigations that will enhance our understanding of these complications, including cardiovascular disease”.
Not only does the relationship between glycaemic therapeutic targets, hypoglycaemia and cardiovascular complications remain “inadequately understood and contentious, despite multiple recent outcomes studies”, but scrutiny of cardiovascular effects associated with glucose-lowering therapies has increased following concerns about rosiglitazone (Avandia) and other drugs in development.
Yet of the 2,439 trials in the researchers’ dataset with available outcomes descriptions listed, only 35 showed a primary outcome related to mortality or clinically significant cardiovascular endpoints (e.g., myocardial infarction or stroke).
And only small numbers of trials reported primary outcomes related to bone metabolism, malignancy or pancreatitis, “despite significant clinical interest in the relationship between these issues and glucose-lowering therapy or diabetes itself”.
One further anomaly observed by the Duke University researchers was in the global distribution of diabetes trials.
For example, the International Diabetes Foundation’s list of the ten locations most affected by diabetes includes multiple Middle Eastern countries in which the prevalence among adults is around 20%. Yet “our analysis suggests that this region is minimallyinvolved in diabetes-related trials”.
A comparison of trial activities in countries with the highest prevalence of diabetes among adults revealed over 500 (out of 1,126) trials in the US.
China, India and Mexico participated in 101–250 trials each but the Russian Federation (12.6 million people affected) and Brazil (12.4 million affected) were involved in only 51–100 registered trials, despite heavy disease burdens.