Increasing interest in cancer therapies and a marked decline in the number of cardiology studies were among the salient trends in the disease focus of clinical trials worldwide over the last few years, a new analysis indicates.
In a review published in Nature, Johan Karlberg of the Clinical Trials Centre at the Li Ka Shing Faculty of Medicine, University of Hong Kong, looked at industry-sponsored Phase II-IV interventional studies first registered with the US-based ClinicalTrials.gov – a “truly global register” – between October 2005 and September 2007.
He found that the therapeutic area with the highest number of registered protocols (824) in the two years under review was oncology, followed by central nervous system (CNS) diseases (670), cardiology (603), infectious diseases (566) and endocrinology (548).
The volume of oncology protocols rose by 3.5% from 405 to 419 between years one and two. Oncology also had the highest proportion of earlier-phase (i.e., Phase II) to overall Phase II and III trials over the two years (Phase IV trials were not counted as they do not appear in all therapeutic categories).
For example, Phase II trials made up 81% of the 43 Phase II/III leukaemia studies registered with ClinicalTrials.gov between October 2005 and September 2007, while Phase II trials accounted for 76.3% of the 138 Phase II/III studies for lung cancer.
As Karlberg pointed out, anticancers are the second largest therapeutic category worldwide, with global pharmaceutical sales of US$34.6 billion in 2006, just behind lipid regulators with sales of US$35.2 billion. Breast cancer (143 studies between October 2005 and September 2007) and lung cancer (138 studies) are the oncology segments where there is most clinical trial activity. While the number of studies for these two indications declined over the two-year period, other cancer types showed strong growth in study volume.
The leading two disorders in the CNS category – depression and schizophrenia – both attracted fewer trials during the review period, as well as relatively few earlier-phase studies (24.5% of 70 registered trials for depression; 35.9% of 61 trials for schizophrenia). However, four other CNS diseases – multiple sclerosis, Alzheimer’s, sleep disorders and attention deficit/hyperactivity disorder – bucked that trend with higher trial volume and a larger proportion of earlier-phase studies. Overall, the number of registered CNS trials dipped by 1.2% from 337 to 333 over the two-year period.
Cardiology slump
Cardiology trials witnessed a much steeper decline, from 346 in year one to 257 in year two. This was despite hypertension ranking second in the number of Phase II-IV trials per disease segment, with a total of 165 studies during the review period. All the same, the volume of hypertension trials fell and only one out of every five Phase II/III studies was a Phase II trial, Karlberg observed.
For a number of years the pharmaceutical industry has conducted large-scale cardiovascular trials for conditions such as hypertension and atherosclerosis, while four cardiovascular drugs were among the top 10 products by global sales in 2006, he noted. And while age-standardised death rates for heart disease have halved, it is still the leading cause of death.
It is therefore “not clear why industry has recently paid less attention to drug development in cardiology, but perhaps it might be considered financially risky to develop a new cardiology drug that will eventually need to compete with current strong market leaders, many of which soon will become generics”, Karlberg suggested. “The need for large, long-term expensive trials might also make the area less favourable compared with others,” he added.
In all, the volume of clinical trials increased for six of the top 10 therapeutic categories during the review period: oncology, endocrinology (from 272 to 276 trials), respiratory diseases (144 to 160), kidney/urology (94 to 114), ophthalmology (85 to 92) and rheumatology (59 to 93), with the last of these categories showing the steepest growth.
The number of studies rose for three of the top 10 diseases: rheumatoid arthritis, asthma and hepatitis, with rheumatoid arthritis (total 2005-2007 = 146 studies) becoming the third most common disease for clinical trials. Top of the list was diabetes, with 356 Phase II-IV clinical trials between October 2005 and September 2007. Diabetes mellitus ranks among the leading six causes of death in the US and the lifetime risk of developing the disease is estimated at 35%, Karlberg pointed out.
