National Academy of Sciences Engineering and Medicine
A Whole Person Approach to Lifting the Burden of Chronic Pain Among Service Members and Veterans
Posted on by Helene M. Langevin, M.D., National Center for Complementary and Integrative Health
Chronic pain and its companion crisis of opioid misuse have taken a terrible toll on Americans. But the impact has been even greater on U.S. service members and veterans, who often deal with the compounded factors of service-related injuries and traumatic stress.
For example, among soldiers in a leading U.S. Army unit, 44 percent had chronic pain and 15 percent used opioids after a combat deployment. That compares to 26 percent and 4 percent, respectively, in the general population [1,2].
This disproportionate burden of chronic pain among veterans [3] and service members led NIH’s National Center for Complementary and Integrative Health (NCCIH) to act. We forged a collaboration in 2017 across NIH, U.S. Department of Defense (DOD), and U.S. Department of Veteran’s Affairs (VA) to establish the Pain Management Collaboratory (PMC).
The PMC’s research focusing on the implementation and evaluation of nondrug approaches for the management of pain is urgently needed in the military and across our entire country. Nondrug approaches require a shift in thinking. Rather than focusing solely on blocking pain temporarily using analgesics, nondrug approaches work with the mind and body to promote the resolution of chronic pain and the long-term restoration of health through techniques and practices such as manual therapy, yoga, and mindfulness-based interventions.
Addressing chronic pain in ways that don’t only rely on drugs means addressing underlying issues, such as joints and connective tissue that lack adequate movement or training our brains to “turn down the volume” on pain signals. Using mind and body practices to reduce pain can help promote health in other ways. Possible “fringe benefits” include better sleep, more energy for physical activity, a better mindset for making good nutritional choices, and/or improved mood.
Indeed, there is a growing body of research on the benefits of nondrug approaches to address chronic pain. What is so powerful about PMC is it puts this knowledge to work by embedding research within military health care settings.
The PMC supports a shared resource center and 11 large-scale pragmatic clinical trials. Within this real-world health care setting, the clinical trials have enrolled more than 8,200 participants across 42 veteran and military health systems. These studies offer both strength in numbers and insights into what happens when learnings from controlled clinical trials collide with the realities of health care delivery and the complexities of daily life. [4]
Central to the PMC partnership is whole person health. Too often, we see health through the prism of separate parts—for example, a person’s cardiovascular, digestive, and mental health problems are viewed as co-occurring rather than as interrelated conditions. A whole person framework—a central focus of NCCIH’s current Strategic Plan—brings the parts back together and recognizes that health exists across multiple interconnected body systems and domains: biological, behavioral, social, and environmental.
The VA’s implementation of a whole health model [5] and their unique closed-loop health care system offers an opportunity to deliver care, conduct research, and illustrate what happens when people receive coordinated care that treats the whole person. In fact, VA’s leadership in this area was the impetus for a recent report by the National Academies of Sciences, Engineering, and Medicine. The report underscored the importance of implementing whole person health care in all settings and for every American.
There are many opportunities ahead for this interagency collaboration. It will help to achieve an important shift, from treating problems one at a time to promoting overall military readiness, resilience, and well-being for U.S. service members and veterans.
Congress appropriated $5 million to NCCIH in fiscal year 2023 to enhance pain research with a special emphasis on military populations. These additional resources will allow NCCIH to support more complex studies in understanding how multiple therapeutic approaches that impact multiple body systems can impact chronic pain.
Meanwhile, programs like the DOD’s Consortium for Health and Military Performance (CHAMP) will continue to translate these lessons learned into accessible pain management information that service members can use in promoting and maintaining their health.
While the PMC’s research program specifically targets the military community, this growing body of knowledge will benefit us all. Understanding how to better manage chronic pain and offering more treatment options for those who want to avoid the risks of opioids will help us all build resilience and restore health of the whole person.
References:
[1] Chronic pain and opioid use in US soldiers after combat deployment. Toblin RL, Quartana PJ, Riviere LA, Walper KC, Hoge CW. JAMA Intern. Med. 2014 Aug;174(8):1400-1401.
[2] Pain and opioids in the military: We must do better. Jonas WB, Schoomaker EB. JAMA Intern. Med. 2014 Aug;174(8):1402-1403
[3] Severe pain in veterans: The effect of age and sex, and comparisons with the general population. Nahin RL. J Pain. 2017 Mar; 18(3):247-254.
[4] Justice and equity in pragmatic clinical trials: Considerations for pain research within integrated health systems. Ali J, Davis AF, Burgess DJ, Rhon DI, Vining R, Young-McCaughan S, Green S, Kerns RD. Learn Health Sys. 2021 Oct 19;6(2): e10291
[5] The APPROACH trial: Assessing pain, patient-reported outcomes, and complementary and integrative health. Zeliadt S, Coggeshall S, Thomas E, Gelman H, Taylor S. Clin. Trials. 2020 Aug;17(4):351-359.
Links:
National Center for Complementary and Integrative Health (NIH)
NCCIH Strategic Plan FY 2021-2025: Mapping a Pathway to Research on Whole Person Health (NIH)
Pain Management Collaboratory (Yale University, New Haven, CT)
Whole Health (U.S Department of Veteran’s Affairs, Washington, D.C.)
Consortium for Health and Military Performance (Department of Defense, Bethesda, MD)
Achieving Whole Health: A New Approach for Veterans and the Nation. (National Academies of Sciences, Engineering, and Medicine, Washington, D.C.)
Note: Dr. Lawrence Tabak, who performs the duties of the NIH Director, has asked the heads of NIH’s Institutes, Centers, and Offices to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 26th in the series of NIH guest posts that will run until a new permanent NIH director is in place.
Advancing Access to Hearing Health Care
Posted on by Debara L. Tucci, M.D., M.S., M.B.A., National Institute on Deafness and Other Communication Disorders
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 [1]. 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. [2].
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 [3] 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 [4].
In 2017, the first randomized, double-blind, placebo-controlled clinical trial comparing an over-the-counter delivery model [5] 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 [6] 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.
References:
[1] Hearing loss prevalence in the United States. Lin F, Niparko J, Ferrucci L. Arch Intern Med. 2011 Nov 14;171(20):1851-1852.
[2] Research drives more accessible, affordable hearing care. Tucci DL, King K. The Hearing Journal. May 2020.
[3] 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.
[4] 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.
[5] 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.
[6] 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.
Links:
National Institute on Deafness and Other Communication Disorders (NIDCD) (NIH)
Funded Research Projects on Accessible and Affordable Hearing Health Care (NIDCD)
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.]
Seeking Consensus on the Use of Population Descriptors in Genomics
Posted on by Eric Green, M.D., Ph.D., National Human Genome Research Institute
Cataloging and characterizing the thousands of genomic variants—differences in DNA sequences among individuals—across human populations is a foundational component of genomics. Scientists from various disciplinary fields compare the variation that occurs within and between the genomes of individuals and groups. Such efforts include attributing descriptors to population groups, which have historically included the use of social constructs such as race, ethnicity, ancestry, and political geographic location. Like any descriptors, these words do not fully account for the scope and diversity of the human species.
The use of race, ethnicity, and ancestry as descriptors of population groups in biomedical and genomics research has been a topic of consistent and rigorous debate within the scientific community. Human health, disease, and ancestry are all tied to how we define and explain human diversity. For centuries, scientists have incorrectly inferred that people of different races reflect discrete biological groups, which has led to deep-rooted health inequities and reinforced scientific racism.
In recent decades, genomics research has revealed the complexity of human genomic variation and the limitations of these socially derived population descriptors. The scientific community has long worked to move beyond the use of the social construct of race as a population descriptor and provide guidance about agreed-upon descriptors of human populations. Such a need has escalated with the growing numbers of large population-scale genomics studies being launched around the world, including in the United States.
To answer this call, NIH is sponsoring a National Academies of Sciences, Engineering, and Medicine (NASEM) study that aims to develop best practices in the use of race, ethnicity, and genetic ancestry in genomics research. The NASEM study is sponsored by 14 NIH institutes, centers, offices, and programs, and the resulting report will be released in February 2023.
Experts from various fields—including genomics, medicine, and social sciences—are conducting the study. Much of the effort will revolve around reviewing and assessing existing methodologies, benefits, and challenges in the use of race and ethnicity and other population descriptors in genomics research. The ad hoc committee will host three public meetings to obtain input. Look for more information regarding the committee’s next public session planned for April 2022 on the NASEM “Race, Ethnicity, and Ancestry as Population Descriptors in Genomics Research” website.
To further underscore the need for the NASEM study, an NIH study published in December 2021 revealed that the descriptors for human populations used in the genetics literature have evolved over the last 70 years [1]. For example, the use of the word “race” has substantially decreased, while the uses of “ancestry” and “ethnicity” have increased. The study provided additional evidence that population descriptors often reflect fluid, social constructs whose intention is to describe groups with common genetic ancestry. These findings reinforce the timeliness of the NASEM study, with the clear need for experts to provide guidance for establishing more stable and meaningful population descriptors for use in future genomics studies.
The full promise of genomics, including its application to medicine, depends on improving how we explain human genomic variation. The words that we use to describe participants in research studies and populations must be transparent, thoughtful, and consistent—in addition to avoiding the perpetuation of structural racism. The best and most fruitful genomics research demands a better approach.
Reference:
[1] Evolving use of ancestry, ethnicity, and race in genetics research—A survey spanning seven decades. Byeon YJJ, Islamaj R, Yeganova L, Wilbur WJ, Lu Z, Brody LC, Bonham VL. Am J Hum Genet. 2021 Dec 2;108(12):2215-2223.
Links:
Use of Race, Ethnicity, and Ancestry as Population Descriptors in Genomics Research (National Academies of Sciences, Engineering, and Medicine)
“Language used by researchers to describe human populations has evolved over the last 70 years.” (National Human Genome Research Institute/NIH)
Genomic Variation Program (NHGRI)
[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 third in the series of NIH institute and center guest posts that will run until a new permanent NIH director is in place.]
Experts Conclude Heritable Human Genome Editing Not Ready for Clinical Applications
Posted on by Dr. Francis Collins
We stand at a critical juncture in the history of science. CRISPR and other innovative genome editing systems have given researchers the ability to make very precise changes in the sequence, or spelling, of the human DNA instruction book. If these tools are used to make non-heritable edits in only relevant tissues, they hold enormous potential to treat or even cure a wide range of devastating disorders, such as sickle cell disease, inherited neurologic conditions, and muscular dystrophy. But profound safety, ethical, and philosophical concerns surround the use of such technologies to make heritable changes in the human genome—changes that can be passed on to offspring and have consequences for future generations of humankind.
Such concerns are not hypothetical. Two years ago, a researcher in China took it upon himself to cross this ethical red line and conduct heritable genome editing experiments in human embryos with the aim of protecting the resulting babies against HIV infection. The medical justification was indefensible, the safety issues were inadequately considered, and the consent process was woefully inadequate. In response to this epic scientific calamity, NIH supported a call by prominent scientists for an international moratorium on human heritable, or germline, genome editing for clinical purposes.
Following on the heels of this unprecedented ethical breach, the U.S. National Academy of Sciences, U.S. National Academy of Medicine, and the U.K. Royal Society convened an international commission, sponsored by NIH, to conduct a comprehensive review of the clinical use of human germline genome editing. The 18-member panel, which represented 10 nations and four continents, included experts in genome editing technology; human genetics and genomics; psychology; reproductive, pediatric, and adult medicine; regulatory science; bioethics; and international law. Earlier this month, this commission issued its consensus study report, entitled Heritable Human Genome Editing [1].
The commission was designed to bring together thought leaders around the globe to engage in serious discussions about this highly controversial use of genome-editing technology. Among the concerns expressed by many of us was that if heritable genome editing were allowed to proceed without careful deliberation, the enormous potential of non-heritable genome editing for prevention and treatment of disease could become overshadowed by justifiable public outrage, fear, and disgust.
I’m gratified to say that in its new report, the expert panel closely examined the scientific and ethical issues, and concluded that heritable human genome editing is too technologically unreliable and unsafe to risk testing it for any clinical application in humans at the present time. The report cited the potential for unintended off-target DNA edits, which could have harmful health effects, such as cancer, later in life. Also noted was the risk of producing so-called mosaic embryos, in which the edits occur in only a subset of an embryo’s cells. This would make it very difficult for researchers to predict the clinical effects of heritable genome editing in human beings.
Among the many questions that the panel was asked to consider was: should society ever decide that heritable gene editing might be acceptable, what would be a viable framework for scientists, clinicians, and regulatory authorities to assess the potential clinical applications?
In response to that question, the experts replied: heritable gene editing, if ever permitted, should be limited initially to serious diseases that result from the mutation of one or both copies of a single gene. The first uses of these technologies should proceed incrementally and with extreme caution. Their potential medical benefits and harms should also be carefully evaluated before proceeding.
The commission went on to stress that before such an option could be on the table, all other viable reproductive possibilities to produce an embryo without a disease-causing alteration must be exhausted. That would essentially limit heritable gene editing to the exceedingly rare instance in which both parents have two copies of a recessive, disease-causing gene variant. Or another quite rare instance in which one parent has two copies of an altered gene for a dominant genetic disorder, such as Huntington’s disease.
Recognizing how unusual both scenarios would be, the commission held out the possibility that some would-be parents with less serious conditions might qualify if 25 percent or less of their embryos are free of the disease-causing gene variant. A possible example is familial hypercholesterolemia (FH), in which people carrying a mutation in the LDL receptor gene have unusually high levels of cholesterol in their blood. If both members of a couple are affected, only 25 percent of their biological children would be unaffected. FH can lead to early heart disease and death, but drug treatment is available and improving all the time, which makes this a less compelling example. Also, the commission again indicated that such individuals would need to have already traveled down all other possible reproductive avenues before considering heritable gene editing.
A thorny ethical question that was only briefly addressed in the commission’s report is the overall value to be attached to a couple’s desire to have a biological child. That desire is certainly understandable, although other options, such an adoption or in vitro fertilization with donor sperm, are available. This seems like a classic example of the tension between individual desires and societal concerns. Is the drive for a biological child in very high-risk situations such a compelling circumstance that it justifies asking society to start down a path towards modifying human germline DNA?
The commission recommended establishing an international scientific advisory board to monitor the rapidly evolving state of genome editing technologies. The board would serve as an access point for scientists, legislators, and the public to access credible information to weigh the latest progress against the concerns associated with clinical use of heritable human genome editing.
The National Academies/Royal Society report has been sent along to the World Health Organization (WHO), where it will serve as a resource for its expert advisory committee on human genome editing. The WHO committee is currently developing recommendations for appropriate governance mechanisms for both heritable and non-heritable human genome editing research and their clinical uses. That panel could issue its guidance later this year, which is sure to continue this very important conversation.
Reference:
[1] Heritable Human Genome Editing, Report Summary, National Academy of Sciences, September 2020.
Links:
“Heritable Genome Editing Not Yet Ready to Be Tried Safely and Effectively in Humans,” National Academies of Sciences, Engineering, and Medicine news release, Sep. 3, 2020.
International Commission on the Clinical Use of Human Germline Genome Editing (National Academies of Sciences, Engineering, and Medicine/Washington, D.C.)
Video: Report Release Webinar , International Commission on the Clinical Use of Human Germline Genome Editing (National Academies of Sciences, Engineering, and Medicine)
National Academy of Sciences (Washington, D.C.)
National Academy of Medicine (Washington, D.C.)
The Royal Society (London)
Gene Drive Research Takes Aim at Malaria
Posted on by Dr. Francis Collins
Malaria has afflicted humans for millennia. Even today, the mosquito-borne, parasitic disease claims more than a half-million lives annually [1]. Now, in a study that has raised both hope and concern, researchers have taken aim at this ancient scourge by using one of modern science’s most powerful new technologies—the CRISPR/Cas9 gene-editing tool—to turn mosquitoes from dangerous malaria vectors into allies against infection [2].
The secret behind this new strategy is the “gene drive,” which involves engineering an organism’s genome in a way that intentionally spreads, or drives, a trait through its population much faster than is possible by normal Mendelian inheritance. The concept of gene drive has been around since the late 1960s [3]; but until the recent arrival of highly precise gene editing tools like CRISPR/Cas9, the approach was largely theoretical. In the new work, researchers inserted into a precise location in the mosquito chromosome, a recombinant DNA segment designed to block transmission of malaria parasites. Importantly, this segment also contained a gene drive designed to ensure the trait was inherited with extreme efficiency. And efficient it was! When the gene-drive engineered mosquitoes were mated with normal mosquitoes in the lab, they passed on the malaria-blocking trait to 99.5 percent of their offspring (as opposed to 50 percent for Mendelian inheritance).
