Clinical Researcher—November 2021 (Volume 35, Issue 8)

PRESCRIPTIONS FOR BUSINESS

Kurt Mussina, MBA

 

There’s no disputing that chronic kidney disease (CKD) is a public health crisis. In the U.S. alone, CKD affects approximately 15% of the population and is a leading cause of death.{1} Internationally, the global estimated prevalence of CKD is 13.4% and the disease “directly affects the global burden of morbidity and mortality worldwide,”{2} according to a 2019 study published in Advances in Experimental Medicine and Biology.

One would expect that with this vast impact on populations, clinical research trials would be in lockstep with prevalence. However, this is not the case. On the contrary: the funding for, and the number of, clinical research trials for CKD lag significantly behind its incidence and behind other diseases. For example, in Q2 2019, there was only one late-stage nephrology study for every 39 cancer studies. As for the funding disparity, the National Institutes of Health (NIH) provided 10 times more funding for cancer than for kidney disease.{3} In fact, it has been noted that nephrology has lagged behind its disease prevalence in the annual percentage of randomized control trials performed globally since records have been kept—more than 50 years.

The number of clinical trials dedicated to kidney disease is striking in how far it lags other therapeutic areas. Unexpectedly, it is not anywhere near commensurate with its prevalence. For instance, between 2016 and 2020, there were 22,486 clinical trials for cancer while there were less than 10% of that amount—only 2,227 clinical trials—for kidney diseases. This has been noted as a growing public health issue (see The Underrecognized Epidemic of Chronic Kidney Disease).

As stated definitively in one study on federal funding for kidney disease research “NIH funding for kidney disease research is inadequate.”{4} As such, it is critically important that this oversight be recognized and addressed immediately to help meet the needs of the 37 million people currently living with CKD in the United States alone.

Research investment often correlates with advances in treatment, which can be clearly seen in cancer and HIV care. According to one source, the American Society of Nephrology’s Research Advocacy Committee “estimated that the [NIH] spent only $30 on research annually for each [CKD)] patient in the [United States] while it spent over $500 for every patient with cancer and over $2,500 per individual with HIV infection. It is therefore not surprising that the cancer and HIV areas have experienced the greatest technological healthcare advances over the last few decades.”{5}

Understanding the Divide

Why does this divide occur? For many, the funding-to-disease ratio may seem obvious: diseases with the heaviest impact on human suffering and/or mortality receive the most funding to advance treatment options. However, this is not necessarily the case—and the reasons for it can be confounding.

An article in The Washington Post offers a thoughtful summary of the, at times, seemingly random allocation of funding: “The differences are an illustration of just how complex—and sometimes surprising—national decisions are about how to allocate research money. It might seem that research dollars should follow public health impact, with the diseases that cause the most harm attracting the most money. Overall, most diseases do follow that general pattern. But the outliers can be significant—HIV currently gets 10% of the NIH budget—and highlight just how complex and baffling this process can be, influenced by factors that range from the amount of scientific opportunity to make progress to the level of human suffering.”{6}

Focusing On the Ethics

If treating all people equitably is one of the fundamentals of medicine, then we must look at the ethics as they pertain to funding and research opportunities. According to an article in the American Journal of Public Health published by researchers from Harvard Medical School, “Kidney disease is an underrecognized but common public health issue that is expensive to treat and disproportionately affects vulnerable populations. As physicians and public policy professionals involved in the treatment and research of kidney disease [we must recognize that] increased research investments are a critical step to reduce the public health burden of kidney disease.”{4}

As with many diseases, the cost of CKD is intense regarding human suffering and from a monetary perspective. Caused primarily by diabetes and high blood pressure, people living with advanced CKD may deal with a plethora of symptoms including lethargy, poor appetite, and poor sleep quality. The statistics on mortality are even more sobering. Using United States Renal Data System (USRDS) data, even when the numbers are adjusted for age, gender, race, comorbidity, and prior hospitalizations, patients with CKD have a 2.3 times higher mortality rate than those without the disease. For those with more advanced CKD (stages 4 or 5), that adjusted mortality rate increases to a 400% increase over patients without CKD.{7} Therefore, males between 40 and 44 with ESRD can expect to live for 10.9 years longer, compared to 36.5 more years for men in the U.S. general population.{8} Notably, the USRDS data use the information from Medicare beneficiaries, which is not a perfect representation of CKD at the population level, but this does highlight issues with this more vulnerable subgroup.

Questions remain regarding the underrepresentation of nephrology when it comes to investment in clinical trials. These are difficult but important questions that deserve exploration, including:

• Does the pharma industry benefit more from conducting research in other areas such as oncology?
• Where do the National Kidney Foundation and American Society of Nephrology fit in addressing this disparity?
• Is it that there simply are no appropriate drug targets in renal disease currently?
• Are the commonly used endpoints the most valuable? How can they be refined, accelerated, or otherwise improved?
• Where is precision medicine in nephrology and why is its development lagging behind other therapeutic areas? What can we do to advance in this area?

Education and Advocacy

There is a great need to better promote current renal disease clinical trials to nephrologists. Beyond the specialists, we need to deliver more wide-reaching education about kidney diseases to the public and to healthcare providers. Improving CKD will rely on a “call to action” advocating for the unique needs of this patient population. We must continue to press for more clinical research trials for the millions of people across all demographics who are living with CKD.

The impact of advocacy will be crucial to engaging patients directly with their kidney health and understanding the impact of CKD. The advantages of early diagnosis and treatment of CKD cannot be overstated. Patients who are diagnosed in the early stages of kidney disease have the chance to make lifestyle changes, learn how to manage their disease, and live longer. We need to convince and recruit these patients for CKD clinical trials. With their help as partners, we can work quickly to uncover innovations for treatment and prevention.

By raising awareness about CKD for scientists, physicians, patients, and funders, we can meaningfully increase the amount of research attention CKD receives. Together, we can move toward a future where CKD has the appropriate amount of clinical study support, relative to its prevalence, needed to reduce its impact. Only by supporting this foundational clinical research can we understand kidney disease and decrease the suffering of those impacted by it.

References

1. Centers for Disease Control and Prevention. Kidney Basics. https://www.cdc.gov/kidneydisease/basics.html
2. Lv JC, Zhang LX. 2019. Prevalence and Disease Burden of Chronic Kidney Disease. In: Liu BC, Lan HY, Lv LL (eds.). Renal Fibrosis: Mechanisms and Therapies. Advances in Experimental Medicine and Biology Springer, Singapore. https://doi.org/10.1007/978-981-13-8871-2_1
3. Building a Global Research Network: Chronic Kidney Disease as a Public Health Crisis. 2019. Frenova.
4. Mendu ML. Federal Funding for Kidney Disease Research: A Missed Opportunity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815960/
5. Impact of Recent Clinical Trials on Nephrology Practice: Are We in a Stagnant Era? https://www.karger.com/Article/Fulltext/495139
6. The Washington Post. Why the Diseases That Cause the Most Harm Don’t Always Get the Most Research Money. https://www.washingtonpost.com/news/wonk/wp/2015/07/17/why-the-diseases-that-cause-the-most-harm-dont-always-get-the-most-research-money/
7. United States Renal Data System. 2020. USRDS Annual Data Report: Epidemiology of kidney disease in the United States.National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. https://adr.usrds.org/2020/chronic-kidney-disease/3-mobidity-and-mortality-in-patients-with-ckd
8. Gulati S, et al. 2020. Chronic Kidney Disease in Children. https://emedicine.medscape.com/article/984358-overview

Kurt Mussina, MBA, is President, Frenova Renal Research, and Senior Vice President, Global Medical Office, FMC.