By 2050, the World Health Organization estimates that more than 700 million people—or one in every 10 people around the globe—will have disabling hearing loss. In the United States alone, hearing loss affects an estimated 30 million people . Hearing loss can be frustrating, isolating, and even dangerous. It is also associated with dementia, depression, anxiety, reduced mobility, and falls.
Although hearing technologies, such as hearing aids, have improved, not everyone has equal access to these advancements. In fact, though hearing aids and other assistive devices can significantly improve quality of life, only one in four U.S. adults who could benefit from these devices has ever used one. Why? People commonly report encountering economic barriers, such as the high cost of hearing aids and limited access to hearing health care. For some, the reasons are more personal. They may not believe that hearing aids are effective, or they may worry about a perceived negative association with aging. .
As the lead federal agency supporting research initiatives to prevent, detect, and treat hearing loss, NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD) conducts and funds research that identifies ways to break down barriers to hearing health care. Decades of NIDCD research informed a recent landmark announcement by the Food and Drug Administration (FDA) creating a new category of over-the-counter (OTC) hearing aids. When the regulation takes effect (expected in 2022), millions of people who have trouble hearing will be able to purchase less expensive hearing aids without a medical exam, prescription, or fitting by an audiologist.
This exciting development has been on the horizon at NIDCD for some time. Back in 2009, NIDCD’s Working Group on Accessible and Affordable Hearing Health Care for Adults with Mild to Moderate Hearing Loss created a blueprint for research priorities.
The working group’s blueprint led to NIDCD funding of more than 60 research projects spanning the landscape of accessible and affordable hearing health care issues. One study showed that people with hearing loss can independently adjust the settings  on their hearing devices in response to changing acoustic environments and, when given the ability to control their own hearing aid settings, they were generally more satisfied with the sound of the devices than with the audiologist fit .
In 2017, the first randomized, double-blind, placebo-controlled clinical trial comparing an over-the-counter delivery model  of hearing aids with traditional fitting by an audiologist also found that hearing aid users in both groups reported similar benefits. A 2019 follow-up study  confirmed these results, supporting the viability of a direct-to-consumer service delivery model. A small-business research grant funded by NIDCD led to the first FDA-approved self-fitting hearing aid.
Meanwhile, in 2016, NIDCD co-sponsored a consensus report from the National Academies of Sciences, Engineering, and Medicine (NASEM). The report, Hearing Health Care for Adults: Priorities for Improving Access and Affordability, which was developed by an independent expert panel, recommended that the FDA create and regulate a new category of over-the-counter hearing devices to improve access to affordable hearing aids for adults with perceived mild-to-moderate hearing loss. These devices will not be intended for children or for adults with more severe hearing loss.
In sum, this targeted portfolio of NIDCD-funded research—together with the research blueprint and the NASEM consensus report—provided a critical foundation for the 2021 FDA rule creating the new class of OTC hearing aids. As a result of these research and policy efforts, this FDA rule will make some types of hearing aids less expensive and easier to obtain, potentially improving the health, safety, and well-being of millions of Americans.
Transforming hearing health care for adults in the U.S. remains a public health priority. The NIH applauds the scientists who provided critical evidence leading to the new category of hearing aids, and NIDCD encourages them to redouble their efforts. Gaps in hearing health care access remain to be closed.
The NIDCD actively solicits applications for research projects to fill these gaps and continue identifying barriers to care and ways to improve access. The NIDCD will also continue to help the public understand the importance of hearing health care with resources on its website, such as Hearing: A Gateway to Our World video and the Adult Hearing Health Care webpage.
 Hearing loss prevalence in the United States. Lin F, Niparko J, Ferrucci L. Arch Intern Med. 2011 Nov 14;171(20):1851-1852.
 Research drives more accessible, affordable hearing care. Tucci DL, King K. The Hearing Journal. May 2020.
 A “Goldilocks” approach to hearing aid self-fitting: Ear-canal output and speech intelligibility index. Mackersie C, Boothroyd A, Lithgow, A. Ear and Hearing. Jan 2019.
 Self-adjusted amplification parameters produce large between-subject variability and preserve speech intelligibility. Nelson PB, Perry TT, Gregan M, VanTasell, D. Trends in Hearing. 7 Sep 2018.
 The effects of service-delivery model and purchase price on hearing-aid outcomes in older adults: A randomized double-blind placebo-controlled clinical trial. Humes LE, Rogers SE, Quigley TM, Main AK, Kinney DL, Herring C. American Journal of Audiology. 1 Mar 2017.
 A follow-up clinical trial evaluating the consumer-decides service delivery model. Humes LE, Kinney DL, Main AK, Rogers SE. American Journal of Audiology. 15 Mar 2019.
Adult Hearing Health Care (NIDCD)
[Note: Acting NIH Director Lawrence Tabak has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the ninth in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.]
As COVID-19 rapidly expanded throughout the world in April 2020, many in the biomedical technology community voiced significant concerns about the lack of available diagnostic tests. At that time, testing for SARS-CoV-2, the coronavirus that causes COVID-19, was conducted exclusively in clinical laboratories by order of a health-care provider. “Over the counter” (OTC) tests did not exist, and low complexity point of care (POC) platforms were rare. Fewer than 8 million tests were performed in the U.S. that month, and it was clear that we needed a radical transformation to make tests faster and more accessible.
By February 2022, driven by the Omicron variant surge, U.S. capacity had increased to a new record of more than 1.2 billion tests in a single month. Remarkably, the overwhelming majority of these—more than 85 percent—were “rapid tests” conducted in home and POC settings.
The story behind this practice-changing, “test-at-home” transformation is deeply rooted in technologic and manufacturing innovation. The NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB), working collaboratively with multiple partners across NIH, government, academia, and the private sector, has been privileged to play a leading role in this effort via the Rapid Acceleration of Diagnostics (RADx®) initiative. On this two-year anniversary of RADx, we take a brief look back at its formation, impact, and potential for future growth.
On April 24, 2020, Congress recognized that testing was an urgent national need and appropriated $1.5 billion to NIH via an emergency supplement . The goal was to substantially increase the number, type, and availability of diagnostic tests in only five to six months. Since the “normal” commercialization cycle for this type of diagnostic technology is typically more than five years, we needed an entirely new approach . . . fast.
The RADx initiative was launched just five days after that challenging Congressional directive . Four NIH RADx programs were eventually created to support technology development and delivery, with the goal of matching test performance with community needs .The first two programs, RADx Tech and RADx Advanced Technology Platforms (ATP), were developed by NIBIB and focused on innovation for rapidly creating, scaling up, and deploying new technologies.
RADx Tech is built around NIBIB’s Point of Care Technologies Research Network (POCTRN) and includes core activities for technology review, test validation, clinical studies, regulatory authorization, and test deployment. Overall, the RADx Tech network includes approximately 900 participants from government, academia, and the private sector with unique capabilities and resources designed to decrease inherent risk and guide technologies from design and development to fully disseminated commercial products.
At the core of RADx Tech operations is the “innovation funnel” rapid review process, popularized as a shark tank . A total of 824 complete applications were submitted during two open calls in a four-month period, beginning April 2020 and during a one-month period in June 2021. Forty-seven projects received phase 1 funding to validate and lower the inherent risk of developing these technologies. Meanwhile, 50 companies received phase 2 contracts to support FDA authorization studies and manufacturing expansion 
Beyond test development, RADx Tech has evolved to become a key contributor to the U.S. COVID-19 response. The RADx Independent Test Assessment Program (ITAP) was launched in October 2021 to accelerate regulatory authorization of new tests as a joint effort with the Food and Drug Administration (FDA) . The ITAP acquires analytical and clinical performance data and works closely with FDA and manufacturers to shave weeks to months off the time it normally takes to receive Emergency Use Authorization (EUA).
The RADx Tech program also created a Variant Task Force to monitor the performance of tests against each new coronavirus “variant of concern” that emerges. This helps to ensure that marketed tests continue to remain effective. Other innovative RADx Tech projects include Say Yes! Covid Test, the first online free OTC test distribution program, and Project Rosa, which conducts real-time variant tracking across the country .
RADx Tech, by any measure, has exceeded even the most-optimistic expectations. In two years, RADx Tech-supported companies have received 44 EUAs and added approximately 2 billion tests and test products to the U.S. capacity. These remarkable numbers have steadily increased from more than16 million tests in September 2020, just five months after the program was established .
RADx Tech has also made significant contributions to the distribution of 1 billion free OTC tests via the government site, COVID.gov/tests. It has also provided critical guidance on serial testing and variants that have improved test performance and changed regulatory practice [9,10]. In addition, the RADx Mobile Application Reporting System (RADx MARS) reduces barriers to test reporting and test-to-treat strategies’ The latter offers immediate treatment options via telehealth or a POC location whenever a positive test result is reported. Finally, the When to Test website provides critical guidance on when and how to test for individuals, groups, and communities.
As we look to the future, RADx Tech has enormous potential to impact the U.S. response to other pathogens, diseases, and future pandemics. Major challenges going forward include improving home tests to work as well as lab platforms and building digital health networks for capturing and reporting test results to public health officials .
A recent editorial published in the journal Nature Biotechnology noted, “RADx has spawned a phalanx of diagnostic products to market in just 12 months. Its long-term impact on point of care, at-home, and population testing may be even more profound .” We are now poised to advance a new wave of precision medicine that’s led by innovative diagnostic technologies. It represents a unique opportunity to emerge stronger from the pandemic and achieve long-term impact.
 NIH mobilizes national innovation initiative for COVID-19 diagnostics, NIH news release, April 29, 2020.
 Rapid scaling up of Covid-19 diagnostic testing in the United States—The NIH RADx Initiative. Tromberg BJ, Schwetz TA, Pérez-Stable EJ, Hodes RJ, Woychik RP, Bright RA, Fleurence RL, Collins FS. N Engl J Med. 2020 Sep 10;383(11):1071-1077.
 We need more covid-19 tests. We propose a ‘shark tank’ to get us there. Alexander L. and Blunt R., Washington Post, April 20, 2020.
 RADx® Tech/ATP dashboard, National Institute of Biomedical Imaging and Bioengineering, NIH.
 New HHS actions add to Biden Administration efforts to increase access to easy-to-use over-the-counter COVID-19 tests. U.S. Department of Health and Human Services Press Office, October 25, 2021.
 A method for variant agnostic detection of SARS-CoV-2, rapid monitoring of circulating variants, detection of mutations of biological significance, and early detection of emergent variants such as Omicron. Lai E, et al. medRxiV preprint, January 9, 2022.
 Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection. Smith RL, et al. J Infect Dis. 2021 Sep 17;224(6):976-982.
 Comparison of rapid antigen tests’ performance between Delta (B.1.61.7; AY.X) and Omicron (B.1.1.529; BA1) variants of SARS-CoV-2: Secondary analysis from a serial home self-testing study. Soni A, et al. MedRxiv preprint, March 2, 2022.
 Reporting COVID-19 self-test results: The next frontier. Health Affairs, Juluru K., et al. Health Affairs, February 11, 2022.
 Radical solutions. Nat Biotechnol. 2021 Apr;39(4):391.
Get Free At-Home COVID Tests (COVID.gov)
When to Test (Consortia for Improving Medicine with Innovation & Technology, Boston)
RADx Programs (NIH)
RADx® Tech and ATP Programs (National Institute of Biomedical Imaging and Biomedical Engineering/NIH)
[Note: Acting NIH Director Lawrence Tabak has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the eighth in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.]
There’s exciting news for people with von Hippel-Lindau (VHL) disease, a rare genetic disorder that can lead to cancerous and non-cancerous tumors in multiple organs, including the brain, spinal cord, kidney, and pancreas. In August 2021, the U.S. Food and Drug Administration (FDA) approved belzutifan (Welireg), a new drug that has been shown in a clinical trial led by National Cancer Institute (NCI) researchers to shrink some tumors associated with VHL disease , which is caused by inherited mutations in the VHL tumor suppressor gene.
As exciting as this news is, relatively few people have this rare disease. The greater public health implication of this advancement is for people with sporadic, or non-inherited, clear cell kidney cancer, which is by far the most common subtype of kidney cancer, with more than 70,000 cases and about 14,000 deaths per year. Most cases of sporadic clear cell kidney cancer are caused by spontaneous mutations in the VHL gene.
This advancement is also a great story of how decades of support for basic science through NCI’s scientists in the NIH Intramural Research Program and its grantees through extramural research funding has led to direct patient benefit. And it’s a reminder that we never know where basic science discoveries might lead.
Belzutifan works by disrupting the process by which the loss of VHL in a tumor turns on a series of molecular processes. These processes involve the hypoxia-inducible factor (HIF) transcription factor and one of its subunits, HIF-2α, that lead to tumor formation.
The unraveling of the complex relationship among VHL, the HIF pathway, and cancer progression began in 1984, when Bert Zbar, Laboratory of Immunobiology, NCI-Frederick; and Marston Linehan, NCI’s Urologic Oncology Branch, set out to find the gene responsible for clear cell kidney cancer. At the time, there were no effective treatments for advanced kidney cancer, and 80 percent of patients died within two years.
Zbar and Linehan started by studying patients with sporadic clear cell kidney cancer, but then turned their focus to investigations of people affected with VHL disease, which predisposes a person to developing clear cell kidney cancer. By studying the patients and the genetic patterns of tumors collected from these patients, the researchers hypothesized that they could find genes responsible for kidney cancer.
Linehan established a clinical program at NIH to study and manage VHL patients, which facilitated the genetic studies. It took nearly a decade, but, in 1993, Linehan, Zbar, and Michael Lerman, NCI-Frederick, identified the VHL gene, which is mutated in people with VHL disease. They soon discovered that tumors from patients with sporadic clear cell kidney cancer also have mutations in this gene.
Subsequently, with NCI support, William G. Kaelin Jr., Dana-Farber Cancer Institute, Boston, discovered that VHL is a tumor suppressor gene that, when inactivated, leads to the accumulation of HIF.
Another NCI grantee, Gregg L. Semenza, Johns Hopkins School of Medicine, Baltimore, identified HIF as a transcription factor. And Peter Ratcliffe, University of Oxford, United Kingdom, discovered that HIF plays a role in blood vessel development and tumor growth.
Kaelin and Ratcliffe simultaneously showed that the VHL protein tags a subunit of HIF for destruction when oxygen levels are high. These results collectively answered a very old question in cell biology: How do cells sense the intracellular level of oxygen?
Subsequent studies by Kaelin, with NCI’s Richard Klausner and Linehan, revealed the critical role of HIF in promoting the growth of clear cell kidney cancer. This work ultimately focused on one member of the HIF family, the HIF-2α subunit, as the key mediator of clear cell kidney cancer growth.
The fundamental work of Kaelin, Semenza, and Ratcliffe earned them the 2019 Nobel Prize in Physiology or Medicine. It also paved the way for drug discovery efforts that target numerous points in the pathway leading to clear cell kidney cancer, including directly targeting the transcriptional activity of HIF-2α with belzutifan.
Clinical trials of belzutifan, including several supported by NCI, demonstrated potent anti-cancer activity in VHL-associated kidney cancer, as well as other VHL-associated tumors, leading to the aforementioned recent FDA approval. This is an important development for patients with VHL disease, providing a first-in-class therapy that is effective and well-tolerated.
We believe this is only the beginning for belzutifan’s use in patients with cancer. A number of trials are now studying the effectiveness of belzutifan for sporadic clear cell kidney cancer. A phase 3 trial is ongoing, for example, to look at the effectiveness of belzutifan in treating people with advanced kidney cancer. And promising results from a phase 2 study show that belzutifan, in combination with cabozantinib, a widely used agent to treat kidney cancer, shrinks tumors in patients previously treated for metastatic clear cell kidney cancer .
This is a great scientific story. It shows how studies of familial cancer and basic cell biology lead to effective new therapies that can directly benefit patients. I’m proud that NCI’s support for basic science, both intramurally and extramurally, is making possible many of the discoveries leading to more effective treatments for people with cancer.
 Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R; MK-6482-004 Investigators. N Engl J Med. 2021 Nov 25;385(22):2036-2046.
 Phase 2 study of the oral hypoxia-inducible factor 2α (HIF-2α) inhibitor MK-6482 in combination with cabozantinib in patients with advanced clear cell renal cell carcinoma (ccRCC). Choueiri TK et al. J Clin Oncol. 2021 Feb 20;39(6_suppl): 272-272.
Von Hippel-Lindau Disease (Genetic and Rare Diseases Information Center/National Center for Advancing Translational Sciences/NIH)
Clear Cell Renal Cell Carcinoma (National Cancer Institute/NIH)
Belzutifan Approved to Treat Tumors Linked to Inherited Disorder VHL, Cancer Currents Blog, National Cancer Institute, September 21, 2021.
The Long Road to Understanding Kidney Cancer (Intramural Research Program/NIH)
[Note: Acting NIH Director Lawrence Tabak has asked the heads of NIH’s institutes and centers to contribute occasional guest posts to the blog as a way to highlight some of the cool science that they support and conduct. This is the first in the series of NIH institute and center guest posts that will run until a new permanent NIH director is in place.]