What happens when you gather dozens of healthcare experts from Massachusetts General, Brigham and Women’s Hospital, and Harvard Medical School and ask them to predict what will change medicine in the next year or so? What you’ll get is the “Disruptive Dozen”—an authoritative list of the 12 innovations mostly likely to have a significant impact on healthcare by the end of 2021.
This list is the result of interviews with 100 medical experts from the facilities noted above (among others), followed by a rigorous selection process, to identify 12 emerging technologies with the potential to “disrupt” healthcare in the next 18 months, one of which could even help us gain some ground against COVID-19. These innovations were presented as part of the World Medical Innovation Forum, held virtually on May 11.
Reducing the burden of prior authorizations
Prior authorizations are intended to flag inappropriate or excessive treatment and help reduce unnecessary healthcare spending. But, for many physicians and patients, the cure (prior authorizations) seems worse than the disease (unnecessary healthcare spending).
“Recent years have seen a sharp rise in procedures subject to prior authorization, inappropriate delays of prior authorization decisions, payment denials for medically necessary care, and unilateral changes in the rules for both patients and clinicians,” said Marcela del Carmen, MD, MPH, professor of obstetrics, gynecology and reproductive biology, Harvard Medical School, and chief medical officer, Massachusetts General Physicians Organization, Boston, MA. “Clearly our system can serve patients and clinicians much better than it currently does.”
Dr. del Carmen described how technological developments are underway to streamline and automate the prior authorization process. This includes standardizing the data shared between healthcare providers and insurance plans. It would also involve transmitting information digitally, directly from patients’ electronic health records. Notably, she said that “plans will be asked to communicate denials in writing immediately and transmit them electronically to allow a timely appeal process to ensue.”
This kind of “end-to-end automation,” as Dr. del Carmen described it, will not only save time but money: approximately $450 million for the healthcare industry.
More importantly, Dr. del Carmen noted that “implementing standards in the above areas is going to lead to a reduction in the significant administrative burden associated with prior authorization, as well as the cost over time, and will better ensure that patients receive access to the services they need.”
Video games for stroke patients
For individuals who’ve had a stroke, recovery often requires intensive physical and cognitive therapy to regain impaired or lost functions. This can be a long and difficult struggle that challenges patients’ willpower and their bank accounts. Now, clinicians are increasingly turning to video games—from standard consumer units to sophisticated virtual reality systems—to help increase patient motivation and compliance, as well as expand access to rehabilitation services.
“In the area of stroke, gaming technologies and virtual reality technologies have recently been shown to be virtually approximate to therapies for upper extremity stroke. In the area of limb dysfunction, virtual technologies are also enhancing sensory impairment as well as motor impairment. What we can do, then, is deliver ‘mass practice’ to people—delivering more to many and changing the world,” said Ross Zafonte, DO, senior vice president, Research Education and Medical Affairs, Spaulding Rehabilitation Network, and Earle P. and Ida S. Charlton professor and chair, Physical Medicine and Rehabilitation, Harvard Medical School.
“These kinds of interventions have [both] a near-term and then a long-term benefit,” Dr. Zafonte explained. “And we're just starting to understand who might benefit the most, how we can deliver it, and what are the worldwide implications of delivering mass practice to many.”
Making cells larger to see them more clearly
Visualizing cells, even with high-resolution microscopes, has its limits. But, scientists have recently developed a new solution to this problem: expansion microscopy. Instead of improving the microscope, they developed methods to physically enlarge or expand cells and tissues of interest.
“I’m sure any pathologist like me can attest to the many times when we have wanted to go just that one magnification step higher...but then find ourselves unable to do so,” said Astrid Weins, MD, PhD, associate pathologist, Brigham Health, and assistant professor of pathology, Harvard Medical School.
“Expansion microscopy is a great tool for researchers and diagnostic pathologists alike that can help us to not only visualize but also to annotate with molecular markers nanometric structures such as, for example, the kidney filtration barrier or small organelles within cells. We can visualize disease processes that then enables us to make better and more precise diagnoses,” she said.
In addition, expansion microscopy can allow researchers to perform tasks more rapidly and without the expense of high-powered microscopes.
Simply put, “Expansion microscopy has the potential to revolutionize diagnostic pathology and disease research,” Dr. Weins said.
First disease-modifying therapy for Alzheimer disease
“Alzheimer’s is devastating. It robs you of your most human qualities: your ability to reason, to abstract, to understand, to make judgments and, especially in the early phases, to remember things that are important to you. So, if there were a treatment approved for Alzheimer’s disease, it would not only be disruptive, it would be absolutely, I think, world-changing,” said Dennis Selkoe, MD, co-director, Ann Romney Center for Neurologic Diseases, Brigham Health, and Vincent and Stella Coates professor of neurologic diseases, Harvard Medical School.
Researchers like Dr. Selkoe anticipate that later this year, the FDA could approve a monoclonal antibody called aducanumab for the treatment of Alzheimer disease. Aducanumab targets amyloid-beta plaques. Many researchers believe that slowing the buildup of these plaques would slow the progression of Alzheimer disease.
The drug is somewhat controversial, though. In two phase 3 studies, aducanumab failed to achieve its primary endpoints. However, a secondary analysis of the data from one of the trials did indicate that the drug showed a significant decrease in cognitive decline in patients treated with the highest dose.
“It's fair to say that it will not be by any means the best agent we ever approve and use. Almost certainly other trials that are already underway will produce other molecules...that will also address the pathology of Alzheimer’s,” Dr. Selkoe said. “But you have to walk before you run, and the advent, potentially in 2020, of the first approved disease-modifying drug for Alzheimer’s is an enormous advance for patients and their families worldwide who are suffering.”
Keeping transplant organs fresher for longer
“Every day, about 20 people will die waiting for an organ transplant,” stated Leonardo Riella, MD, PhD, medical director, Vascularized Composite Tissue Transplantation, Brigham Health, and associate physician, Harvard Medical School.
With current methods, most organs have to be transplanted within 12 hours before they’re no longer viable, he explained.
Now, a new technique involves supercooling the organ to -6 °C but preventing it from freezing. Freezing can cause permanent damage to the organ, rendering it unusable. The supercooling method keeps organs healthier for longer.
“So, the number of organs that potentially would be discarded and now could be used for transplantation is significantly increased,” Dr. Riella said. “Not only that, these organs are also more preserved, and this will impact not only complications after transplant but also it’s going impact survival—how long this organ is going to last in the long term.”
New therapeutic options for sickle cell disease
“Sickle cell disease is one of the blood diseases that is truly like a curse. It destroys the lives of the people who have it, with chronic pain syndromes and devastating complications that really disrupt the ability to have an organized life,” said David Scadden, MD, director, Center for Regenerative Medicine, Massachusetts General Hospital, co-director, Harvard Stem Cell Institute, and Gerald and Darlene Jordan professor of medicine, Harvard Medical School.
The cause of sickle cell disease has been known for more than 50 years, yet only one drug—hydroxyurea—has been widely used for treating it.
“That has really changed very recently,” Dr. Scadden noted, citing two new medications for sickle cell disease approved by the FDA within just the past few months.
The first is Adakveo (crizanlizumab-tmca, Novartis), which prevents sickled red blood cells from accumulating and blocking small blood vessels. The other new medicine is Oxbryta (voxelotor), which helps prevent red blood cells from forming into a sickle shape.
“These are two developments that will truly have a major impact on the lives of patients, but also have...now opened the door for a whole host of new agents that are being tested,” Dr. Scadden said.
Gene therapies transform treatment of rare, devastating diseases
After decades of investigation, the first gene therapies were finally approved, starting in 2017. Following these first successes, a new wave of gene therapies is now arriving for the treatment of rare genetic conditions.
“The ones we are referring to here [include] gene therapy for cerebral adrenoleukodystrophy, a devastating disorder of the brain that causes loss of all neurological function or death in a few years, and affects mostly boys,” said Patricia Musolino, MD, PhD, co-director, Pediatric Cerebrovascular Service, Massachusetts General Hospital, and assistant professor, Harvard Medical School.
She explained that this gene therapy is a one-time procedure that consists of using a viral vector to bring the “normal” gene into the cells that produce circulatory immune cells. Correcting these cells halts the inflammation in the brain that causes the destruction of the myelin sheath that protects neurons.
“Preliminary results published in The New England Journal of Medicine already show that this therapy will be changing the lives of these patients. These boys are now preserving their neurological function,” Dr. Musolino said. “Not only that, they are sparing themselves from side effects that standard therapy with bone marrow transplantation will bring.”
The other gene therapy coming to the fore is a treatment for hemophilia A. In this chronic bleeding disorder, patients are missing the gene that produces blood-clotting factor VIII. As a result, patients suffer from frequent and sometimes life-threatening bleeds in the joints, brain, and other parts of the body.
The gene therapy for this disease takes a different strategy, with the corrective gene inside an adeno-associated viral vector that is injected directly into the patient’s liver cells, according to Dr. Musolino. This jump-starts the liver cells into producing blood-clotting factor VIII to sufficient levels to stop chronic bleeding.
New tools to help aging eyes and ears
Age-related disorders affecting vision and hearing are very common in older Americans. Fortunately, new innovations are helping clinicians to better diagnose and treat these ubiquitous conditions.
“Optical coherence tomography, or OCT, is an imaging technology that ophthalmologists use to diagnose and monitor retinal diseases, and it’s especially important now in making treatment decisions for age-related macular degeneration where our patients are needing monthly or every-other-month injections of drugs into the eye,” explained Joan Miller, MD, chief of ophthalmology, Massachusetts Eye & Ear, Massachusetts General Hospital, and Boston Hospital, and David Glendenning Cogan professor of ophthalmology and chair, Department of Ophthalmology, Harvard Medical School.
However, it can be difficult for vision-impaired seniors to get into the ophthalmologist’s office for testing on a frequent basis. Enter the home-based OCT, in which patients can test themselves with an OCT at home—as often as daily—and upload their results to the cloud. Artificially-intelligent (AI) algorithms then alert the doctor when changes warrant further evaluation.
Besides decreasing the number of office visits, Dr. Miller explained that “we may actually be able to improve patients’ vision outcomes, because if they’re able to monitor more frequently, we can really personalize when they need to come in for treatment.”
“I think it will lead to better compliance and better treatment timing for patients,” she added.
Regarding age-related hearing loss, there are currently no FDA-approved treatments for sensorineural hearing loss, except hearing aids and cochlear implants. But, new drugs are now in the pipeline that may reduce hearing loss or even lead to recovery, Dr. Miller noted.
Solving the problem of infection in total joint replacements
An increasing number of people are undergoing total joint replacement, and most recover with no major problems. But, for about 2% of patients, an infection of the joint can be a nightmare.
“To treat those patients, it costs about $1.6 billion in the US alone, and the mortality rate is comparable to certain types of cancer,” said Orhun Muratoglu, PhD, Alan Gerry scholar and director, Harris Orthopaedics Lab, Massachusetts General Hospital, and professor, Orthopedic Surgery, Harvard Medical School.
But Dr. Muratoglu and co-investigators came up with an innovative solution. They developed implants that actively prevent bacterial adhesion.
“We discovered methods to do this by adding certain therapeutic agents to these permanent implants, and these implants then elute [ie, release] these therapeutic agents into the joint space,” he explained. “Our ultimate goal is to eliminate infection by treating everyone [prophylactically] with these modified implants.”
Digital management of chronic disease
Chronic disease is an enormous challenge in the United States, and the problem is only getting worse. In 2016, the United States spent more than a trillion dollars caring for patients with heart disease, diabetes, cancer, and other chronic conditions.
A solution to the problem must involve not only lowering costs but also improving care and, ultimately, averting preventable chronic diseases from developing. Interestingly, the COVID-10 pandemic has accelerated the adoption of just such a solution: digital management of chronic disease.
“One of the things that is obvious from the last few weeks and months in the current coronavirus pandemic is that patients really quite like remote care because it helps them manage their chronic disease in the context of the rest of their lives,” said Calum MacRae, MD, PhD, vice chair for scientific innovation, Department of Medicine, Boston Hospital, and associate professor of medicine, Harvard Medical School.
Remote care, as Dr. MacRae envisions it, is not simply a video chat between doctor and patient, although that is a central part of it. This approach involves frequent remote interactions with patients, provided by a multidisciplinary team and enabled by AI and digital device technology, to help patients get better care and to help them become more involved in their own care.
“When you start to add in information from remote sensors—whether those are wearables, or sensors in somebody’s home, or in their bathroom scale, or in their mirror, or in their car—you begin to realize how collecting more information about yourself in a private and secure fashion can also be a really important piece of understanding your health and wellness,” Dr. MacRae said. “And if that information can be gathered in a way that the system can then learn about you over time, suddenly you have the ability to trigger interventions not when you feel unwell or you go to see your physician, but when [your] actual biology starts to change.”
Not only will such an approach help individuals to improve themselves, but the healthcare system overall might be able to improve itself continuously by design, he predicted.
Harnessing technology to reduce health disparities
A multitude of factors influence health, such as genes, diet, exercise, and more. But, the environments and societies in which we live also play roles in our health, and they’re factors that are becoming increasingly more recognized. Addressing these factors—including issues such as quality housing, access to healthy food, and the ability to exercise safely outdoors—may not only improve health for people impacted but also minimize the health disparities that can arise from social and economic inequalities.
“When we think about health equity and technology, there are two roads that we should take: One is that, as we have advanced healthcare technology...we often leave behind different corners of our population—people who aren’t able to access the technology that we’ve already developed,” said Thomas Sequist, MD, chief patient experience and equity officer, Partners HealthCare System, and professor of medicine and healthcare policy, Harvard Medical School. So, this “road” involves bringing up those who have been left behind.
“The second road that I often think about in terms of health technology and inequities, is thinking about how can we use technology in new ways to specifically address the inequities that we see.”
A variety of health technology startups are now working to address these two “roads” of health equity. For example, some companies are developing software to help clinicians connect with community and social service providers. This platform enables clinicians to coordinate and track patients to help them gain access to community-based support programs. Other organizations are addressing specific barriers—such as lack of transportation—that prevent patients from having access to healthcare.
Battling COVID-19: maps, technology, and AI
One of the first efforts to use geographic methods to track disease occurred in 1874 when physician John Snow used mapping techniques and statistical analysis to trace the source of a cholera outbreak to a public water pump in London’s Soho district.
Nearly 150 years later, public health researchers are applying similar, though much more sophisticated, methods to track COVID-19 in real time. With the aid of computers and statistical algorithms, their tracking tool gathers self-reported information from the general public, anonymized and mapped by ZIP codes, to trace the spread of the disease and identify potential hotspots.
“I think that this technology is really incredible to think about how we can leverage it in this time of COVID-19,” said Rochelle Walensky, MD, chief, Division of Infectious Diseases, Massachusetts General Hospital, and professor of medicine, Harvard Medical School.
For instance, apps, smartphones, and other technologies could be used for monitoring temperatures, symptoms, and social distancing among all the children in a particular school or school system.
Contact tracing—a major concern right now—could be another important way to use this technology, Dr. Walensky suggested.
“There have been studies published that demonstrate that our current method of contact tracing—where we find a person who has disease and then we have to interview that person and go find all of the people that they’ve been in contact with—takes a huge amount of manpower and also a lot of time,” she said. “And it's been speculated that we don't have the time or the manpower that that will take.”
Instead, Dr. Walensky suggested that “we might be able to use mobile apps to do this contact tracing for us to...detect who people have been in contact with and then quickly notify them to let them know.”