Health

FDA Approval of a SARS-CoV-2 Vaccine and Surrogate Endpoints

Daniel Walsh, Ph.D, MJLST Staffer

The emergence of the SARS-CoV-2 virus has thrown the world into chaos, taking the lives of more than a million worldwide to date. Infection with SARS-CoV-2 causes the disease COVID-19, which can have severe health consequences even for those that do not succumb. An unprecedented number of vaccines are under development to address this challenge. The goal for any vaccine is sterilizing immunity, which means viral infection is outright prevented. However, a vaccine that provides only partially protective immunity will still be a useful tool in fighting the virus. Either outcome would reduce the ability of the virus to spread, and hopefully reduce the incidence of severe disease in those who catch the virus. An effective vaccine is our best shot at ending the pandemic quickly.

For any vaccine to become widely available in the United States, it must first gain approval from the Food and Drug Administration (FDA). Under normal circumstances a sponsor (drug manufacturer) seeking regulatory approval would submit an Investigational New Drug (IND) application, perform clinical trials to gather data on safety and efficacy, and finally file a Biologics License Application (BLA) if the trials were successful. The FDA will review the clinical trial data and make a determination as to whether the benefits of the therapy outweigh the risks, and if appropriate, approve the BLA. Of course, degree of morbidity and mortality being caused by COVID-19 places regulators in a challenging position. If certain prerequisites are met, the FDA as the authority to approve a vaccine using an Emergency Use Authorization (EUA). As pertaining to safety and efficacy, the statutory requirements for issuing an EUA are lower than normal approval. It should also be noted that an initial approval via EUA does not preclude eventual normal approval.  Full approval of the antiviral drug remdisivir is an example of this occurrence.

In any specific instance, the FDA must conclude that a reason for using the EUA process (in this case SARS-CoV-2):

can cause a serious or life-threatening disease or condition . . . based on the totality of scientific evidence available . . . including data from adequate and well-controlled clinical trials, if available, it is reasonable to believe that . . . the product may be effective in diagnosing, treating, or preventing [SARS-CoV-2] . . . the known and potential benefits of the product, when used to diagnose, prevent, or treat [SARS-CoV-2], outweigh the known and potential risks of the product . . . .

21 USC 360bbb-3(c). On its face, this statute does not require the FDA to adhere to the full phased clinical trial protocol in grating an EUA approval. Of course, the FDA is free to ask for more than the bare minimum, and it has wisely done so by issuing a set of guidance documents in June and October. The FDA indicated that, at the minimum, a sponsor would need to supply an “interim analysis of a clinical endpoint from a phase 3 efficacy study;” that the vaccine should demonstrate an efficacy of at least 50% in a placebo controlled trial; that phase 1 and 2 safety data should be provided; and that the phase 3 data “should include a median follow-up duration of at least two months after completion of the full vaccination regimen” (among other requirements) in the October guidance.

It is clear from these requirements that the FDA is still requiring sponsors to undertake phase 1, 2, and 3 trials before FDA will consider issuing an EUA, but that the FDA is not going to wait for the trials to reach long term safety and efficacy endpoints, in an effort to get the public access to a vaccine in a reasonable time frame. The Moderna vaccine trial protocol, for example, has a study period of over two years. The FDA also has a statutory obligation to “efficiently review[] clinical research and take[] appropriate action . . . in a timely manner.” 21 USC § 393(b)(1).

One method of speeding up the FDA’s assessment of efficacy is a surrogate endpoint. Surrogate endpoints allow the FDA to look at an earlier, predictive metric of efficacy in a clinical trial when it would be impractical or unethical to follow the trial to its actual clinical endpoint. For example, we often use blood pressure as a surrogate endpoint when evaluating drugs intended to treat stroke. The FDA draws a distinction between candidate, reasonably likely, and validated surrogate endpoints. The latter two can be used to expedite approval. However, in its June guidance, the FDA noted “[t]here are currently no accepted surrogate endpoints that are reasonably likely to predict clinical benefit of a COVID-19 vaccine . . . .  [and sponsors should therefore] pursue traditional approval via direct evidence of vaccine safety and efficacy . . . .” This makes it unlikely surrogate endpoints will play any role in the initial EUAs or BLAs for any SARS-CoV-2 vaccine.

However, as the science around the virus develops the FDA might adopt a surrogate endpoint as it has for many other infectious diseases. Looking through this list of surrogate endpoints, a trend is clear. For vaccines, the FDA has always used antibodies as a surrogate endpoint. However, the durability of the antibody response to SARS-CoV-2 has been an object of much concern. While this concern is likely somewhat overstated (it is normal for antibody levels to fall after an infection is cleared), there is evidence that T-cells are long lasting after infection with SARS-CoV-1, and likely play an important role in immunity to SARS-CoV-2. It is important to note that T-Cells (which coordinate the immune response and some of which can kill virally infected cells) and B-Cells (which produce antibody proteins) are both fundamental, and interdependent pieces of the immune system. With this in mind, when developing surrogate endpoints for SARS-CoV-2 the FDA should consider whether it is open to a more diverse set of surrogate endpoints in the future, and if so, the FDA should communicate this to sponsors so they can begin to build the infrastructure necessary to collect the data to ensure vaccines can be approved quickly.

 


It’s a Small World, and Getting Smaller: The Need for Global Health Security

Madeline Vavricek, MJLST Staffer

The word “unprecedented” has been used repeatedly by every news organization and government official throughout the last several months. Though the times that we live in may be unprecedented, they are far from being statistically impossible—or even statistically unlikely. Based on the most recent implementation of the International Health Regulations released by the World Health Organization (WHO) in 2005, more than 70% of the world is deemed unprepared to prevent, detect, and respond to a public health emergency. The reality of this statistic was evidenced by the widespread crisis of COVID-19. As of September 29, 2020, the global COVID-19 death toll passed one million lives, with many regions still reporting surging numbers of new infections. Experts caution that the actual figure could be up to 10 times higher.

The impact of COVID-19 has made pandemic preparedness paramount in a way modern times have yet to experience. While individual countries look inward towards their own national response to the coronavirus, it is apparent now more than ever that global issues demand global solutions. The ongoing COVID-19 pandemic indicates a need for increased resiliency in public health systems to manage infectious diseases, a factor known as global health security.

The Centers for Disease Control and Prevention (CDC) defines global health security as “the existence of strong and resilient public health systems that can prevent, detect, and respond to infectious disease threats, wherever they occur in the world.” Through global health security initiatives, organizations such as the Global Health Security Agenda focus on assisting individual countries in planning and resource utilization to address gaps in health security in order to benefit not only the health and welfare of the individual countries, but the health and welfare of the world’s population as a whole. The Coronavirus has been reported in 214 countries, illustrating that one country’s health security can impact the health security of dozens of others. With the ever-increasing spread of globalization, it is easier for infectious diseases to spread more than ever before, making global health security even more essential than in the past.

Global health security effects more than just health and pandemic preparedness worldwide. Johnson & Johnson Chief Executive Officer Alex Gorsky recently stated that “[g]oing forward, we’re going to understand much better that if we don’t have global public health security, we don’t have national security, we don’t have economic security and we will not have security of society.” As demonstrated by COVID-19, failure to adequately prevent, detect, and respond to infectious diseases has economic, financial, and societal impacts. Due to the Coronavirus, the Dow Jones Industrial Average and the Financial Times Stock Exchange Group saw their biggest quarterly drops in the first three months of the year since 1987; industries such as travel, oil, retail, and others have all taken a substantial hit in the wake of the pandemic. Unemployment rates have increased dramatically as employers are forced to lay off employees across the majority of industries, amounting in an estimated loss of 30 million positions in the United States alone. Furthermore, Coronavirus unemployment has been shown to disproportionally affect women workers and people of color. The social and societal effects of COVID-19 continue to emerge, including, but not limited to, the interruption of education for an estimated 87% of students worldwide and an increase in domestic violence rates during shelter in place procedures. The ripple effect caused by the spread of infectious disease permeates nearly every aspect of a nation’s operation and its people’s lives, well beyond that of health and physical well-being.

With a myriad of lessons to glean from the global experience of COVID-19, one lesson countries and their leaders must focus on is the future of global health security. The shared responsibility of global health security requires global participation to strengthen health both at home and abroad so that future infectious diseases do not have the devastating health, economic, and social consequences that the coronavirus continues to cause.

 


Can the Legal System Help Combat COVID-19

Amanda Jackson, MJLST Staffer

As the novel coronavirus, COVID-19, continues its global rampage, the United States has been hard hit.  Now third with respect to number of new cases, there is little evidence to show that the case count will decrease any time soon.  If Italy provides any indication of what is to come, the United States is only going to be hit harder by the life-threatening virus.  Both federal government and local governments have taken drastic measures to combat the spread of COVID-19, including state-wide shelter-in-place orders, closing schools and universities, banning dining in at bars and restaurants, and moving non-essential businesses to work-from-home models.

As the confirmed cases continue to rise, so does uncertainty and uneasiness among the nation and the world as a whole.  What will fix this crisis?  How long will these measures be in place?  How many more people will get sick and potentially pass away from the virus?  What will happen to the economy?  Will my loved ones be okay?  The questions never seem to end.  Luckily, however, there are some answers as to how different laws, administrative agencies, and regulations in place in the United States can aid in the fight against the quickly spreading coronavirus.

First, the Defense Production Act (DPA) can alleviate shortages in medical equipment.  As concern about the novel virus itself grows, concern for the availability of necessary supplies and equipment also seems to grow at record speeds.  A lack of masks and other personal protective equipment for healthcare workers, a shortage in ventilators and beds for sick patients, and even a need for healthcare workers and hospital space are becoming more prevalent as the COVID-19 crisis continues.   The DPA, a Korean War-era law, enables the federal government to require private companies to provide for the needs of national defense.  The DPA may not be able to satisfy the need for healthcare workers and hospital space, but it can allow the federal government to direct manufacturers to produce the desperately needed medical equipment for healthcare workers and patients.  However, the President must invoke the DPA in order for it to make a difference, and as of right now, the DPA has not been invoked to aid in the fight against coronavirus.  Although some companies have increased or altered production to help restock the necessary equipment, it remains unclear whether that alone, without invoking the DPA, will be enough to meet the needs of the United States in the coming weeks.  Even so, the DPA provides a robust option to fulfill the needs of the nation in the fight against the pandemic.

Second, the Federal Drug Administration’s (FDA) and the National Institute of Health’s (NIH) ability to fast track vaccines and therapeutic drugs can speed up development of a COVID-19 vaccine or therapy.  Called an Emergency Use Authorization (EUA), the FDA is able to authorize emergency use of an unapproved product or an unapproved use of an approved product under a declaration of a public health, domestic, or military emergency, or a material threat.  The evidence required for approval of an EUA is that the product “may be effective” to treat, diagnose, or prevent the conditions associated with the declaration.  This is a lower standard than the “effectiveness” standard used for typical FDA approvals, a process that takes on average twelve years to go from a new drug in a laboratory to a drug on a pharmacy shelf.  In determining whether to approve the EUA, the Commissioner has to determine that the known and potential benefits of the product outweigh the risks associated with the product, while also considering the threat prompting the emergency declaration.  Fortunately, the FDA has already issued multiple EUAs with respect to the novel coronavirus, such as for tests to detect COVID-19.  The FDA has also instituted flexible measures outside of EUAs that enable states to take a more prominent role than typically allowed.  For example, the FDA is now allowing states to approve COVID-19 tests without requiring FDA approval or an EUA.  Moreover, NIH is also fast-tracking development of a coronavirus vaccine, with a Phase I clinical trial of the vaccine candidate having already begun.

Third, declarations of major disaster areas will open up emergency funds to help states and local governments respond to an outbreak.  Major disaster area declarations are often requested when a disaster exceeds the response capabilities of state and local governments under extremely severe circumstances.  Major disaster area declarations enable a wide range of federal assistance for both individuals and public infrastructure.  With respect to coronavirus, the President has already declared New York and other hard-hit states as major disaster areas, the first time in United States history that a major disaster has been declared for a public health threat.  The declaration enables the federal government to pay for a majority of the states’ costs and mobilize the Federal Emergency Management Agency (FEMA) to deploy assistance in the state, among other methods of assistance.

Fourth, shelter-in-place orders by local governments may reduce the spread of the virus.  Shelter-in-place orders mandate that residents stay in their homes, except for essential trips (e.g., to the grocery store or a pharmacy).  Many shelter-in-place orders also force all non-essential businesses to close.  These orders are generally constitutional under a state’s police power.  At least eight states and many cities have issued shelter-in-place orders as a means to flatten the curve and reduce the impact of coronavirus on society and the healthcare system.  Some law enforcement officials appear to be taking the orders very seriously, breaking up parties in violation of the shelter-in-place rules or stating that the orders will be “strictly enforced.”

Moreover, there are multiple bills working their way through the federal government that will hopefully provide some more answers and relief for the American people.  Although those options are only a few of the tools in the government’s toolbox, if used properly, they can help the nation combat COVID-19.


Privacy, Public Facebook Posts, and the Medicalization of Everything

Peter J. Teravskis, MD/JD Candidate, MJLST Staffer

Medicalization is “a process by which human problems come to be defined and treated as medical problems.” Medicalization is not a formalized process, but is instead “a social meaning embedded within other social meanings.” As the medical domain has expanded in recent years scholars have begun to point to problems with “over-medicalization” or “corrupted medicalization.” Specifically, medicalization is used to describe “the expansion of medicine in people’s lives.” For example, scholars have problematized the medicalization of obesity, shynesshousing, poverty, normal aging, and even dying, amongst many others. The process of medicalization has become so pervasive in recent years that various sociologists have begun to discuss it as the medicalization “of everyday life,” “of society,”  “of culture,” of the human condition, and “the medicalization of everything”—i.e. turning all human difference into pathology. Similarly, developments in “technoscientific biomedicine” have led scholars to blur the line of what is exclusively “medical” into a broader process of “biomedicalization.”

Medicalization does not carry a valence of “good” or “bad” per se: medicalization and demedicalization can both restrict and expand personal liberties. However, when everyday living is medicalized there are many attendant problems. First, medicalization places problems outside a person’s control: rather than the result of choice, personality, or character, a medicalized problem is considered biologically preordained or “curable.” Medicalized human differences are no longer considered normal; therefore, “treatment” becomes a “foregone conclusion.” Because of this, companies are incentivized to create pharmacological and biotechnological solutions to “cure” the medicalized problem. From a legal perspective, Professor Adele E. Clarke and colleagues note that through medicalization, “social problems deemed morally problematic . . . [are] moved from the professional jurisdiction of the law to that of medicine.” This process is referred to, generally, as the “medicalization of deviance.” Further, medicalization can de-normalize aspects of the human condition and classify people as “diseased.”

Medicalization is important to the sociological study of social control. Social control is defined as the “mechanisms, in the form of patterns of pressure, through which society maintains social order and cohesion.” Thus, once medicalized, an illness is subject to control by medicinal interventions (drugs, surgery, therapy, etc.) and a sick people are expected to take on the “sick role” whereby they become the subjects of physicians’ professional control. A recent example of medical social control is the social pressure to engage in hygienic habits, precautionary measures, and “social distancing” in response to the novel coronavirus, COVID-19. The COVID-19 pandemic is an expressly medical problem; however, when normal life, rather than a viral outbreak, is medicalized, medical social control becomes problematic. For example, the sociologist Peter Conrad argues that medical social control can take the form of “medical surveillance.” He states that “this form of medical social control suggests that certain conditions or behaviors become perceived through a ‘medical gaze’ and that physicians may legitimately lay claim to all activities concerning the condition” (quoting Michel Foucault’s seminal book The Birth of the Clinic).

The effects of medical social control are amplified due to the communal nature of medicine and healthcare, leading to “medical­legal hybrid[]” social control and, I argue, medical-corporate social control. For example, employers and insurers have interests in encouraging healthful behavior when it reduces members’ health care costs. Similarly, employers are interested in maximizing healthy working days, decreasing worker turnover, and maximizing healthy years, thus expanding the workforce. The State has similar interests, as well as interests in reducing end-of-life and old age medical costs. At first glance, this would seem to militate against overmedicalization. However, modern epidemiological methods have revealed the long term consequences of untreated medical problems. Thus, medicalization may result in the diversion of health care dollars towards less expensive preventative interventions and away from more expensive therapy that would help later in life.

An illustrative example is the medicalization of obesity. Historically, obesity was not considered a disease but was a socially desirable condition: demonstrating wealth; the ability to afford expensive, energy-dense foods; and a life of leisure rather than manual labor. Changing social norms, increased life expectancy, highly sensitive biomedical technologies for identifying subtle metabolic changes in blood chemistry, and population-level associations between obesity and later-life health complications have contributed to the medicalization of this conditions. Obesity, unlike many other conditions, it not attributable to a single biological process, rather, it is hypothesized to result from the contribution of multiple genetic and environmental factors. As such, there is no “silver bullet” treatment for obesity. Instead, “treatment” for obesity requires profound changes reaching deep into how a patient lives her life. Many of these interventions have profound psychosocial implications. Medicalized obesity has led, in part, to the stigmatization of people with obesity. Further, medical recommendations for the treatment of obesity, including gym membership, and expensive “health” foods, are costly for the individual.

Because medicalized problems are considered social problems affecting whole communities, governments and employers have stepped in to treat the problem. Politically, the so-called “obesity epidemic” has led to myriad policy changes and proposals. Restrictions designed to combat the obesity epidemic have included taxes, bans, and advertising restrictions on energy-dense food products. On the other hand, states and the federal government have implemented proactive measures to address obesity, for example public funds have been allocated to encourage access to and awareness of “healthy foods,” and healthy habits. Further, Social Security Disability, Medicare and Medicaid, and the Supplemental Nutrition Assistance Program have been modified to cope with economic and health effects of obesity.

Other tools of control are available to employers and insurance providers. Most punitively, corporate insurance plans can increase rates for obese employees.  As Abby Ellin, writing for Observer, explained “[p]enalizing employees for pounds is perfectly legal [under the Affordable Care Act]” (citing a policy brief published in the HealthAffairs journal). Alternatively, employers and insurers have paid for or provided incentives for gym memberships and use, some going so far as to provide exercise facilities in the workplace. Similarly, some employers have sought to modify employee food choices by providing or restricting food options available in the office. The development of wearable computer technologies has presented another option for enforcing obesity-focused behavioral control. Employer-provided FitBits are “an increasingly valuable source of workforce health intelligence for employers and insurance companies.” In fact, Apple advertises Apple Watch to corporate wellness divisions and various media outlets have noted how Apple Watch and iPhone applications can be used by employers for health surveillance.

Indeed, medicalization as a pretense for technological surveillance and social control is not exclusively used in the context of obesity prevention. For instance, the medicalization of old age has coincided with the technological surveillance of older people. Most troubling, medicalization in concert with other social forces have spawned an emerging field of technological surveillance of mental illness. Multiple studies, and current NIH-funded research, are aimed at developing algorithms for the diagnosis of mental illness based on data mined from publicly accessible social media and internet forum posts. This process is called “social media analysis.” These technologies are actively medicalizing the content of digital communications. They subject peoples’ social media postings to an algorithmic imitation of the medical gaze, whereby, “physicians may legitimately lay claim to” those social media interactions.  If social media analysis performs as hypothesized, certain combinations of words and phrases will constitute evidence of disease. Similar technology has already been coopted as a mechanism of social control to detect potential perpetrators of mass shootings. Policy makers have already seized upon the promise of medical social media analysis as a means to enforce “red flag” laws. Red flag laws “authorize courts to issue a special type of protection order, allowing the police to temporarily confiscate firearms from people who are deemed by a judge to be a danger to themselves or to others.” Similarly, it is conceivable that this type of evidence will be used in civil commitment proceedings. If implemented, such programs would constitute a link by which medical surveillance, under the banner of medicalization, could be used as grounds to deprive individuals of civil liberty, demonstrating an explicit medical-legal hybrid social control mechanism.

What protections does the law offer? The Fourth Amendment protects people from unreasonable searches. To determine whether a “search” has occurred courts ask whether the individual has a “reasonable expectation of privacy” in the contents of the search. Therefore, whether a person had a reasonable expectation of privacy in publicly available social media data is critical to determining whether that data can be used in civil commitment proceedings or for red flag law protective orders.

Public social media data is, obviously, public, so courts have generally held that individuals have no reasonable expectation of privacy in its contents. By contrast, the Supreme Court has ruled that individuals have a reasonable expectation of privacy in the data contained on their cell phones and personal computers, as well as their personal location data (cell-site location information) legally collected by third party cell service providers. Therefore, it is an open question how far a person’s reasonable expectation of privacy extends in the case of digital information. Specifically, when public social media data is used for medical surveillance and making psychological diagnoses the legal calculation may change. One interpretation of the “reasonable expectation of privacy” test argues that it is an objective test—asking whether a reasonable person would actually have a privacy interest. Indeed, some scholars have suggested using polling data to define the perimeter of Fourth Amendment protections. In that vein, an analysis of the American Psychiatric Association’s “Goldwater Rule” is illustrative.

The Goldwater Rule emerged after the media outlet “Fact” published psychiatrists’ medical impressions of 1964 presidential candidate Barry Goldwater. Goldwater filed a libel suit against Fact, and the jury awarded him $1.00 in compensatory damages and $75,000 in punitive damages resulting from the publication of the psychiatric evaluations. None of the quoted psychiatrists had met or examined Goldwater in person. Subsequently, concerned primarily about the inaccuracies of “diagnoses at a distance,” the APA adopted the Goldwater Rule, prohibiting psychiatrists from engaging in such practices. It is still in effect today.

The Goldwater Rule does not speak to privacy per se, but it does speak to the importance of personal, medical relationships between psychiatrists and patients when arriving at a diagnosis. Courts generally treat those types of relationships as private and protect them from needless public exposure. Further, using social media surveillance to diagnose mental illness is precisely the type of diagnosis-at-a-distance that concerns the APA. However, big-data techniques promise to obviate the diagnostic inaccuracies the 1960s APA was concerned with.

The jury verdict in favor of Goldwater is more instructive. While the jury found only nominal compensatory damages, it nevertheless chose to punish Fact magazine. This suggests that the jury took great umbrage with the publication of psychiatric diagnoses, even though they were obtained from publicly available data. Could this be because psychiatric diagnoses are private? The Second Circuit, upholding the jury verdict, noted that running roughshod over privacy interests is indicative of malice in cases of libel. Under an objective test, this seems to suggest that subjecting public information to the medical gaze, especially the psychiatrist’s gaze, unveils information that is private. In essence, applying big-data computer science techniques to public posts unveils or reveals private information contained in the publicly available words themselves. Even though the public social media posts are not subject to a reasonable expectation of privacy, a psychiatric diagnosis based on those words may be objectively private. In sum, the medicalization and medical surveillance of normal interactions on social media may create a Fourth Amendment privacy interest where none previously existed.


Undocumented Americans and a Pathway to Health Care Coverage

Jacob Hauschild, MJLST Staffer

In a June Democratic Primary debate, moderator Savannah Guthrie asked the field of candidates who would provide undocumented immigrants access to health care coverage. When all ten candidates raised their hands, the issue of health care access for undocumented immigrants was pushed to the forefront of the health care reform debate.

Despite this apparent unanimity, Democrats are far from aligned on the issue—never mind the policy’s poor popularity among voters. But lacking from the public discourse is due attention to how undocumented immigrants currently engage with our health care system.

Health care coverage is usually attained by U.S. citizens through one of three sources: (1) employer-sponsored insurance (ESI), (2) public health care programs (for example, Medicare and Medicaid), and (3) the individual market. Not all of these doors are open to undocumented immigrants, however. While some do have access to ESI, undocumented immigrants are generally prohibited from enrolling in federal public programs such as Medicare and Medicaid[1], and they are also not permitted to purchase health insurance on the federal or state-based marketplaces. While they can buy short- or long-term coverage directly from an insurer or an insurance broker, this coverage is often prohibitively expensive. Therefore, undocumented immigrants who cannot access health care insurance through their employer are often left with no coverage options; in fact, undocumented immigrants are uninsured at a rate of about 45%, compared to the only 8% of citizens who are uninsured.

The lack of access to health care coverage causes lower utilization of health care services, particularly preventative care. Some uninsured patients have access to income-based Community Health Centers—which are an “important source of primary care” for the uninsured—but these facilities often lack “stable revenue streams [and] sufficient staffing support.” Further, most hospital systems have “Charity Care” programs, but these programs tend to focus on paying for health care costs already incurred, rather than promoting use of preventative care to help patients stay healthy and reduce future cost.

Low access to preventative care services results in poorer health care outcomes and more complex and expensive health care needs later in life for the undocumented and other uninsured groups. That care is often delivered in the emergency room, where care for an emergency medical condition cannot be denied due to ability to pay. The financial burden of this uncompensated care weighs on the entire health care system and poses a detriment to the financial and physical wellness of our communities. Further, the financial loss from this uncompensated care is ultimately spread among all health care consumers—for example, through increased taxes; diversion of public funds from other programs; and, as is often claimed, increases to the costs of private health insurance—and is leading to the insolvency of health care systems in communities with fewer commercially insured patients.

Keeping in mind the impact of high uninsurance among undocumented immigrants, the manner in which health care access is “expanded” is of tremendous consequence. Proposals like Joe Biden’s only allow for undocumented immigrants to purchase coverage at full cost on the ACA marketplaces, without access to tax subsidies. Due to excessive cost and the fact that undocumented immigrants live in poverty at twice the rate of U.S. born citizens, it is unlikely for such a policy change to reduce uninsurance amongst this population. Meanwhile, plans like Bernie Sanders’ Medicare-for-All apparently cover all residents of the United States, regardless of immigration status. Such expansive health care reform is controversial in its own right, and should Medicare-for-All or a similar proposal advance through Congress in the future, it seems likely that access—and the extent of that access—to undocumented immigrants will be a dividing point among Democrats, as well as a nonstarter among many Republicans.

Yet the issue merits attention. Because the health care costs of undocumented immigrants are spread across the health care system regardless of whether or not they have access to coverage, it is good policy to curb those costs with preventative care, particularly when we consider the specific health care needs of the population, which in the modern era include significant trauma. A solution could take several forms, ranging from full access to the marketplace and its tax credits; to Medicaid benefits for income-eligible, undocumented children; to expanded funding for Community Health Centers and culturally competent outreach. Whatever that solution may be, it will affect not only the 10.7 million undocumented immigrants in the United States but also each and every health care consumer in the country.

[1] Sixteen states permit undocumented women who are pregnant and meet income guidelines to temporarily access Medicaid by utilizing federal CHIP funding to cover the unborn child, and income-eligible individuals who receive emergency services in an emergency room may be eligible for Medicaid to exclusively cover those costs.


Will the Vaping Industry Go Up in Smoke?

Stephen Wood, MJLST Staffer

It’s no secret that vaping has become increasingly popular. The number of users has increased from 7 million in 2011 to 41 million as of 2018. The total market is now worth an estimated $19.3 billion. Less clear is the future of industry regulation in light of the recent respiratory illnesses linked to vaping. On September 24, 2019, the Centers for Disease Control and Prevention reported that vaping was attributed to 805 illnesses and 12 deaths. Pressure is building on the industry’s major players. In the last week, we have seen the cancellation of a merger between two of the largest tobacco companies, Altria and Philip Morris, and the release of the CEO of Juul, Kevin Burns.

However, the respiratory illnesses associated with vaping haven’t been linked to a specific product, and it is unclear what the long-term effects of vaping are. Because of this uncertainty, some states have implemented blanket restrictions on the sale of vaping products, President Trump has proposed new regulations, and the CDC has issued warnings regarding their safety. This is blindsiding the industry, which has been free from regulation by the FDA until recently.

Vaping devices, also known as electronic nicotine delivery systems (ENDS), became subject to the FDA’s regulatory scheme for all tobacco products on August 8, 2016. The Deeming Rule placed ENDS in the same category of products as cigarettes and other traditional tobacco products, which have been regulated under the Family Smoking Prevention and Tobacco Control Act since 2009. For this reason, the minimum age for purchasing ENDS is 18 years old, and the marketing, manufacturing, and distribution of ENDS is heavily regulated.

Juul, in particular, has come under fire for its marketing strategies. Among other claims, many lawsuits allege that the company specifically targeted minors through its use of social media and distribution of enticing flavors. These practices have also been the focal point of the recent surge of state regulations, which “are filling what many see as a regulatory void caused by federal inaction.” For example, in Michigan, Governor Gretchen Whitmer implemented an emergency ban, limiting the sale of vaping products to those which are tobacco flavored. New York did the same but exempted menthol from the ban. Massachusetts, notably, implemented a four-month emergency ban on all products. President Trump’s proposed ban, on the other hand, would be limited to flavored products.

If President Trump’s proposal is adopted, the industry would see an estimated 80% loss in sales. It will be interesting to see what the regulatory landscape looks like once the smoke clears.

 


Treating Depression with Ketamine? How The Investment Was Made

Hunter Moss, MJLST Staffer

Depression is a serious mental disorder that afflicts millions of Americans each year. One in three of these individuals struggles to find a treatment method that alleviates their condition, and are aptly said to suffer from treatment-resistant depression. In the most severe cases, treating depression can be a life or death decision—depression is the leading cause of over 41,000 suicides every year. For those dealing with depression, every day is a struggle to persevere and try to regain a sense of normalcy.

A new therapy for treatment-resistant depression was approved by the Food and Drug Administration (FDA) earlier this week, one that could help those that have been unable to find relief elsewhere. The unexpected source of the therapy is esketamine. If the name of this drug sounds familiar, it is because the name is based on, and molecularly similar to, the street drug named ketamine. While originally synthesized in the 1960’s as an anesthetic and first used widely in the Vietnam War, ketamine is now known as a party drug, providing the user with mild hallucinations and a sense of euphoria. Due to its dangerous side-effects and potential for abuse, ketamine was placed on the Schedule III of the United States Controlled Substance Act in August of 1999.

In the early 1990’s, researchers at Yale University first recognized the potential for ketamine to treat the symptoms of depression. Since then, scientists sought to confirm the viability of ketamine as a treatment option for individuals who did not experience relief from other treatment methods. A 2012 study out of Baylor College of Medicine proved just that: 85% of patients with severe depression reported the treatment to be effective. Unlike selective serotonin reuptake inhibitors (SSRIs), which are most commonly prescribed to treat depression and can take weeks to build in a patient’s system before becoming effective, ketamine can provide nearly immediate relief with its full effect being felt in as little as two days.

With the science firmly in place, the next hurdle advocates of ketamine faced was of perception—in the eyes of the FDA and the public alike. Radical clinics began to emerge across the country to provide patients suffering from treatment-resistant depression with a safe, heavily-monitored environment to undergo care. Because ketamine had yet to be recognized as a potential aid for depression by the FDA, clinic physicians would often have to prescribe the drug under the guise of using it as an anesthetic. The “don’t ask, don’t tell” approach to a new treatment for a severe mental disorder created some inevitable quandaries for both doctors and patients, who would be unable to receive insurance coverage for a non-FDA approved treatment program.

While the medical community was well aware of the healing potential of ketamine, pharmaceutical companies were reluctant to make the investment. The average price-tag of a clinical trial for the FDA is $19m. There is certainly a market for the drug with countless Americans suffering from depression. The issue holding pharmaceutical companies back is related to patent law. In order to receive a patent, the proposed invention must be novel—and considering that ketamine has been around for nearly sixty years, that would be an impossible claim to make. Without patent protection, the multi-million dollar investment is bad economics for big pharma, even if the trials could provide relief for millions of Americans.

So why did Janssen Pharmaceuticals, the developer of a treatment method for depression based on ketamine, make the investment and receive FDA approval for its new drug Sprovato? The answer is because Sprovato is esketamine, a sufficiently different molecule from ketamine to be patentable. Certain molecules can be left-handed and have right-handed doppelgangers. While it is beyond the scope of this blog piece (and the ability of its author) to explain the difference between the two, esketamine is the left-handed version of ketamine’s right hand. The deviation between the molecules is a significant enough difference to pass the novelty requirement necessitated by the U.S. Patent and Trademark Office (USPTO). While there is some debate as to whether esketamine is as effective as its counterpart, esketamine passed the FDA’s clinical trials and, for the most part, has been received as a viable alternative to ketamine treatment. This development could help legitimize the countless ketamine clinics that have emerged across the United States over the last few years, yielding a promising new alternative for those struggling with severe depression. At the same time, the story of ketamine raises questions about the roles of several actors in the health care system, specifically pharmaceutical companies, the FDA and the USPTO, in delaying the introduction of life saving medication in order to adhere their respective financial and regulatory requirements.


“Juuling”: Gen Z’s Alleged Addiction May Mean Major Legal Problems for E-Cigarette Companies

By: Jack Kall, Minnesota Journal of Law, Science & Technology Vol. 20 Staffer

With every new week comes new headlines regarding Gen Z and their latest craze. After years of Millennials being cast as the generation responsible for everything wrong in the world, (Business Insider’s list of 19 things Millennials are killing, including everything from homeownership, banks, football, and oil to beer, napkins, cereal, and bars of soap; NPR describing how Millennials are killing Applebee’s; Forbes claiming Millennials might kill home-cooked meals and kitchens) it seems the media has found a new culprit, Gen Z! Gen Z’s supposed addiction to e-cigarettes, specifically to the JUUL brand, is common among the headlines.

Depending on how you define the generation, Gen Z includes anyone born in the years starting with 1995–2000 and ending between 2014–25. Pew Research has yet to name or define the end date of Gen Z, but it defines the “Post-Millennial generation” as those born 1997 and later.

No matter how you define Gen Z, it includes high school students, many of whom are under the legal tobacco consumption age of 18. High schoolers have been a major reason for both the rise of e-cig popularity and for giving JUUL Labs major market share in the e-cig industry. Browse through social media pages popular within the Gen Z community and you’ll inevitably see numerous posts about “Juuling.” However, Gen Z isn’t alone in its supposed obsession with e-cigs, as Leonardo DiCaprio (a member of Gen X) has long been known to appreciate vaping (e.g., 1, 2, 3).

JUUL Labs, which launched in 2015, has been repeatedly investigated for targeting minors through its advertising and sued for targeting teens with false claims of product safety. In 2017, Consumer Reports found that teens who vape are seven times more likely to turn to regular cigarettes. Additionally, the CDC has declared e-cig use among young people a public health concern.

As further research is published, JUUL should expect be the main target of continued legal action. One current case, a nationwide class action with ten named plaintiffs aged above 13, alleges in part that JUUL’s decision to market through social media was aimed at soliciting those under the legal smoking age. Another case, filed on behalf of a high school sophomore, alleges that JUUL is commonplace among his school, including use “on the school bus, in the bathrooms, outside of school and even in class.”

JUUL Labs will hope to continue to have success while under major legal scrutiny for its marketing practices. JUUL, importantly, hopes it can continue to show growth following its impressive financial valuation (most recently raising $1.2 billion in a financing round that valued the company at over $15 billion).


Act Fast! Get Access To Your Genetic Past, Present, and Future For One Low, Low Price

Hannah Mosby, MJLST Staffer

 

It’s Saturday morning, and you’re flipping through channels on your TV when you hear the familiar vocal inflections of an infomercial. For three monthly installments of $19.99, you can get access to your complete genetic ancestry, and any genetic predispositions that might impact your health—both now and in the future. From the comfort of your couch, you can order a kit, provide a DNA sample, and poof. . . a month or two later, you know everything you could ever want to know about your own genetic makeup. Sounds a little far-fetched, right?

 

Wrong. It’s 2017, and genetic testing kits are not only readily accessible to the public—they’re relatively inexpensive. Curious about whether you’re really German and Irish? Wondering if you—like your mother and her grandmother—might develop Alzheimer’s disease? Companies like 23andMe have you covered. The company advertises kits that cover both ancestry and certain health risks, and has recorded the sale of over 2 million testing kits. Maybe you’ve heard your friend, your coworker, or your sister talking about these genetic tests—or maybe they’ve already ordered their own kit.

 

What they’re probably not talking about, however, is the host of bioethical implications this sort of at-home genetic testing has. To some, ancestry may be cocktail party conversation, but to others, heritage is an enormous component of their personal identity. Purchasing a genetic testing kit may mean suddenly finding out that your ancestry isn’t what you thought it was, and consumers may or may not understand the emotional and psychological implications of these kinds of results. Genetic health risks present an even bigger ethical challenge—it’s all too easy to mistake the word “predisposition” for a diagnosis. Unless consumers are thoroughly educated about the implications of specific gene variants, companies like 23andMe aren’t providing useful health data—they’re providing enormously impactful information that the average consumer may not be equipped to understand or cope with.

 

It’s also easy to forget about the data privacy concerns. According to 23andMe’s commercial website, “23andMe gives you control over your genetic information. We want you to decide how your information is used and with whom it is shared.” That sounds nice—but is that “meaningful choice” masked in legal-ese? Existing federal regulation bars discriminatory use of genetic information by insurance companies and employers, but how does that affect other entities, if it does at all? Third-party access to this highly personal information is under-regulated, and it can’t be adequately safeguarded by “consent” without thoroughly explaining to consumers the potential implications of third-party disclosure.

 

It’s easy to get wrapped up in new and exciting biotechnology—especially when it’s publicly accessible. And we should be excited. . . accessibility and transparency in a field as intimidating as genetics can be is worth celebrating. Further, genetic testing brings with it a host of preventative health and personal benefits. However, it also raises some ethical and regulatory concerns, and it’s important to make sure our enthusiasm—as consumers, but also as entrepreneurs—for genetic technology doesn’t outpace the regulatory systems available to govern it.


Health in the Fast Lane: FDA’s Effort to Streamline Digital Health Technology Approval

Alex Eschenroeder, MJLST Staffer

 

The U.S. Food and Drug Administration (FDA) is testing out a fast-track approval program to see if it can accommodate the pace of innovation in the technology industry and encourage more ventures into the digital health technology space. Dr. Scott Gottlieb M.D., Commissioner of the FDA, announced the fast-track pilot program—officially named the “Pre-Cert for Software Pilot Program” (Program)—on July 27, 2017. Last week, the FDA announced the names of the nine companies it selected out of more than 100 applicants to participate in the Program. Companies that made it onto the participant list include tech giants such as Apple and Samsung, as well as Verily Life Sciences—a subsidiary of Alphabet, Inc. The FDA also listed smaller startups, indicating that it intends to learn from entities at various stages of development.

The FDA idea that attracted applicants from across the technology industry to the Program is roughly analogous to the TSA Pre-Check Program. With TSA Pre-Check certification, travelers at airports get exclusive access to less intensive pre-boarding security procedures because they submitted to an official background check (among other requirements) well before their trip. Here, the FDA Program completes extensive vetting of participating technology companies well before they bring a specific digital health technology product to market. As Dr. Gottlieb explained in the July Program announcement, “Our new, voluntary pilot program will enable us to develop a tailored approach toward this technology by looking first at the . . . developer, rather than primarily at the product (as we currently do for traditional medical products).” If the FDA determines through its review that a company meets necessary quality standards, it can pre-certify the company. A pre-certified company would then need to submit less information to the FDA “than is currently required before marketing a new digital health tool.” The FDA even proposed the possibility of a pre-certified company skipping pre-market review for certain products, as long as the company immediately started collecting post-market data for FDA to confirm safety and effectiveness.

While “digital health technology” does not have a simple definition, a recently announced Apple initiative illustrates what the term can mean and how the FDA Program could encourage its innovation. Specifically, Apple recently announced plans to undertake a Heart Study in collaboration with Stanford Medicine. Through this study, researchers will use “data from Apple Watch to identify irregular heart rhythms, including those from potentially serious heart conditions like atrial fibrillation.” Positive research results could encourage Apple, which “wants the Watch to be able to detect common heart conditions such as atrial fibrillation”, to move further into FDA regulated territory. Indeed, Apple has been working with the FDA, aside from the Program, to organize the Heart Study. This is a critical development, as Apple has intentionally limited Watch sensors to “fitness trackers and heart rate monitors” to avoid FDA regulation to date. If Apple receives pre-certification through the Program, it could issue updates to a sophisticated heart monitoring app or issue an entirely different diagnostic app with little or no FDA pre-market review. This dynamic would encourage Apple, and companies like it, to innovate in digital health technology and create increasingly sophisticated tools to protect consumer health.