Few drug companies want to develop therapies for markets as small as the CKD population.
Nephrologists want to improve outcomes and quality of life for renal disease patients through research, but we are faced with major hurdles. One of these is the number of patients with CKD and end-stage renal disease (ESRD).
In 2007, an estimated 16.8% of U.S. adults had CKD and 485,012 patients had ESRD (www.cdc.gov/mmwr/preview/mmwrhtml/mm5608a2.htm, accessed on September 18, 2008). Compared with other patient populations, such as individuals with diabetes, hypertension, or hypercholesterolemia, the CKD and ESRD populations are relatively small.
Few pharmaceutical companies are willing to dedicate resources to developing therapies for such a limited market. Despite the morbidity and mortality associated with CKD and ESRD, these conditions are viewed by drug manufacturers as unique disease processes that don’t warrant dedicated investigation of newer compounds.
Much of the expense of bringing new drugs to market is related to the costs of clinical trials. Nephrology research is typical with respect to the expenditures required to conduct good clinical studies but also unique in the additional costs that dialysis companies impose for conducting research in their facilities.
Additionally, the rigorous studies that can establish and define therapeutic efficacy have been limited to an all-comers approach. Powering a study to find a difference among un-selected patients with CKD or ESRD enhances generalizability but fails to incorporate the heterogeneity of the disease processes and clinical scenarios seen in these populations.
When a trial produces neutral or negative findings, researchers often seek to identify clinical subgroups that did experience a benefit. To pharmaceutical companies, however, such subgroups represent a smaller segment of an already limited market, potentially causing manufacturers to shy away from funding subgroup analyses.
In recent years, there has been a movement within drug development programs to do research in developing countries, where the cost per subject is lower, allowing for reduced trial expenditures both directly through decreased payments and indirectly through shorter trials. Trials can be conducted more quickly because of faster startup and enrollment.
That saves money on study staff, a major driving force of trial budgets. In fact, 20%-30% of global clinical trials are currently being done in developing countries (Appl Clin Trials. 2004;13:84-92). Patients in these countries benefit from access to experimental and potentially efficacious therapies that otherwise would be unavailable. But there are disadvantages as well.
In countries where the care of CKD or ESRD patients may be dissimilar in terms of lesser access to care or where there is a decreased ability to achieve the benchmarks of care present in developed countries, it might be appropriate in non-renal studies to exclude patients with such comorbidities as CKD or ESRD due to issues of questionable generalizability. This further limits data on which to base the application of drug therapies to the CKD and ESRD populations.