June 07, 2021

Deja Vu All Over Again?

 

The big news in geriatrics this week was the FDA  approval granted to a drug against Alzheimer's disease, the first new drug in 20 years. It reminded me of the day in 1986 when the initial report about what would be the very first FDA-approved drug against this disease appeared.


It was November 13, 1986 and I had been a practicing geriatrician for four years. My weekly copy of the New England Journal of Medicine had arrived right on time, as it did every Thursday. I scanned the table of contents and one article immediately jumped out at me. It had the suitably serious, scientific-sounding title “Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type.”

 

During four years  of clinical practice—plus a year of geriatrics fellowship and three years doing an internal medicine residency—I had encountered patients with what we then called “SDAT,” (senile dementia of the Alzheimer’s type) and which we now simple call Alzheimer’s disease. The cognitive impairments of dementia were to me, to family members of the afflicted, and often to the affected themselves, among the saddest of the many disorders that develop among older individuals. Death, while also very sad, was part of the natural order of things, especially when it came after a long and rich life. But dementia in general and Alzheimer’s disease in particular was devastating because it attacked personality; some would say it assaulted personhood itself. While I would go on to spend much of my career thinking about how best to enable people with dementia (as well as those with physical frailty) to live meaningful lives despite their limitations, I recognized then and continue to believe today that the condition is a scourge that we should strive to prevent, eradicate, or at least ameliorate.

 

The medication described in the 1986 NEJM article would ultimately be approved by the FDA under the name of Tacrine for treatment of mild to moderate Alzheimer’s disease; it would be supplanted by its first cousin, the drug donepezil, brand name Aricept; and Aricept would top $2 billion in US sales by the time it came off patent in 2013. The story of the drug’s development says volumes about Americans’ desperation for a medical fix to Alzheimer’s, about big business, and about our regulatory system. Both the similarities and the differences between the Tacrine story and the tale of the new drug approved by the FDA for the treatment of Alzheimer’s are illuminating.


That 1986 study ostensibly showing that Tacrine led to improvements in cognition as well as to overall functioning was based on a whopping 17 patients, only 14 of whom actually completed the study. Its lead author was Dr. William Summers, a psychiatrist at UCLA medical center who had never before published anything of importance and had done very little research altogether. The scientific community immediately began questioning not only Summers’ credibility but also his methodology. Did the 17 patients actually have compelling evidence of an Alzheimer’s diagnosis? Did the “global assessment rating” used to measure outcomes translate into meaningful improvement?

 

After Summers filed for FDA approval for his drug,the FDA investigated Summers and his lab. The agency issued a rare “interim report” in 1991 in which it criticized Summers for the absence of documentation that the study was actually performed as  claimed in the NEJM  paper.  It questioned the randomization process and whether the physicians were, as asserted by Summers, blinded to what drug the patient was receiving. The best the FDA could say was that there was “no clear evidence of purposeful misrepresentation.”

 

In response, the public vilified the FDA, claiming the agency was “heartlessly impeding the relief of suffering.” David Kessler, the FDA director, received hate mail.

 

Approval of the drug came, but only after the release in 1992 of a larger more carefully conducted study by the “Tacrine Collaborative.” The trial lasted for 12 weeks and was carried out at 23 centers involving 468 patients. The results, published in the Journal of the American Medical Association, showed a statistically significant improvement in cognition and in overall function, whether measured by physicians or caregivers. And so, the first drug was approved for treatment of Alzheimer’s disease. Sales soared.  But questions continued to plague use of the drug—a subsequent study, for example, testing the effectiveness of a higher dose of the drug,  found that the higher dose was more effective than lower doses—but more than 2/3 of the patients dropped out of the study. Tacrine was soon effectively replaced by donepezil (Aricept), another cholinesterase inhibitor that differed only from Tacrine in that it is taken once a day rather than twice and has fewer gastrointestinal side effects. Patients and families demanded these drugs, which were soon followed by chemically slightly different but no more effective agents such as Excelon; the drug companies advertised them widely and made a small fortune on their  sales; but clinicians remained skeptical. I, for one, believe that the cholinesterase inhibitors are next to useless. None of the numerous studies of the drugs carried out since 1986 have persuaded me otherwise.

 

Fast forward to 2021 and the approval by the FDA of aducanumab under the brand name of Aduhelm. This is a completely different kind of treatment. Tacrine and Aricept are cholinesterase-inhibitors: they work by increasing the level of the neurotransmitter, acetylcholine, which is dramatically reduced in Alzheimer’s. They are given orally and were never terribly expensive, although Aricept got cheaper when the generic version became available. Side effects, particularly in the case of Aricept, are modest and consist of nausea and very rarely of liver enzyme abnormalities.  The new drug, by contrast, is a monoclonal antibody that works to mop up deposits of beta-amyloid from the brain, the chemical widely thought to cause Alzheimer’s disease. It must be given intravenously once a month. The average yearly cost will be set at $56,000. Two years ago, its manufacturer, Biogen, stopped an ongoing clinical trial of the drug after interim analysis failed to demonstrate efficacy. The drug company then re-analyzed the data and claimed it was effective after all, but an FDA Advisory Panel, convened in  November, 2020 unanimously concluded there was insufficient evidence of significant benefit to proceed. 

 

Multiple other monoclonal antibodies targeting beta amyloid have also failed, leading some to suggest that by the time these drugs are given to patients, it’s already too late. Or maybe beta amyloid is a marker for the disease and not the cause of the disease. It is in this setting, that the FDA approval of aducanumab is something of a surprise.


What is particularly striking about today’s FDA approval is that it is not based on the clinical effectiveness of the drug. Rather, it is based on its ability to clear the brain of amyloid deposits. There is a long tradition of requiring that drugs cause improvement in clinically meaningful outcomes, not just in “surrogate markers.” Cholesterol-lowering drugs were approved based on their ability to prevent heart attacks, not just on their ability to lower blood cholesterol levels. Antihypertensive drugs were approved based on their effectiveness in reducing strokes, not just on their capacity to lower blood pressure. To be sure, the FDA is holding off on full, unconditional approval until it sees the results of a yet to be performed large clinical trial demonstrating long-term benefit of amyloid plaque reduction. In the meantime, anxious patients and their families will submit to monthly injections of a drug that has been shown to cause symptomatic brain swelling, manifested by nausea, vomiting, visual problems, headaches and sometimes small strokes, in 40 percent of cases. 

We are a long way from the trials and tribulations of tacrine, but in the end, is the tale of aducanumab any less disturbing? In both cases, there was enormous pressure by the public to approve a drug that offered hope, some hope, however slim, of ameliorating this terrible disease. In both cases, the FDA, after seemingly acting based on scientific considerations alone, seemed to succumb to external pressures. And in both cases, the pharmaceutical industry stood to gain enormously by release of the drug. The FDA currently has an acting director: President Biden has yet to name a new, permanent head. Maybe it's time for the FDA director to become a civil servant, selected by the FDA members, rather than a political appointee. At the very least, the new director, when chosen, should take a long hard look at decision-making within the organization.

May 21, 2021

Tiptoeing Towards the End Zone

On January 12, 2006, I launched this blog, which I first called “Perspectives on Aging” and, a number of years later, reincarnated as “Life in the End Zone.” Initially, the frequency of my posts was erratic but then, a year and a half after the blog’s inception, NY Times columnist Paula Span gave “Perspectives” a boost, recommending it along with just one other blog on aging in her weekly column, “The New Old Age.”  She sent me an email at the time, telling me that my readers would expect predictability and that I was now obligated to post weekly and on a fixed schedule. 

For years, I faithfully followed Paula Span’s advice, but more recently have been writing only sporadically. Every few years I contemplated retiring the blog, but then I would get an email out of the blue from a reader who told me how useful she found a particular post. Two months before his death in 2019, the distinguished ethicist Dan Callahan, who I was privileged to call a friend, commented in his last email to me that he “particularly appreciated” my piece on “dignity and the insensitive nurses”—a post I wrote about an episode at an area nursing home in which nurses and nursing assistants were cruel and callous to a resident they disliked. How could I stop writing when I received this kind of feedback?

After I published the 400th post I thought surely this was a good time to stop. But then came the pandemic, which disproportionately affected older people. There was a great deal to say, so on March 2, 2020, I began writing more regularly. I wrote about the devastating Covid outbreaks in nursing homes; I wrote about the role of telemedicine; I wrote about vaccines. And then, gradually, as the pandemic began to recede, as vaccination rates in older people soared, and as Covid disappeared from nursing homes, I again found I had less to say. So, when I saw Jane Brody’s column in the NY Times this week, “A Birthday Milestone: Turning 80,” I was inspired.  I would write about my own birthday milestone—last week I turned 70.

 

What Jane Brody says, in a nutshell, is that “the secret of a happy, vibrant old age” is to “strive to do what you love for as long as you can do it.” But she says more about what it takes to live a long and fulfilling life.” First, exercise. Without regular exercise, she opines, “you can expect to experience a loss of muscle strength and endurance, coordination and balance, flexibility and mobility, bone strength and cardiovascular and respiratory function.”  Translated into geriatric lingo, what she is saying is that to preserve function, the ability to walk, to do errands, even to dress and bathe without help, regular exercise is important. Next in importance, she says, is “quality fuel,” or a good diet. Here Brody is vague, but stresses avoiding “ultra-processed foods” and eating plenty of fruit and vegetables.  Finally, there are “attitude, motivation, and perspective” about which she does not further elaborate.

 

What Brody is talking about is “successful aging.” For years I have wanted to write about successful aging, as it was called by Rowe and Kahn in their landmark 1987 work of the same title. The idea of successful aging has been the subject of both intense criticism and passionate enthusiasm. One problem is that we all want to lead a “good life,” but we may have very different ideas of what that looks like. Sometimes, what we think we need for a good life turns out not to be what we need at all: people who have a life-altering medical condition, whether Parkinson’s or osteoarthritis or chronic obstructive pulmonary disease may wish they hadn’t developed that disorder but find that they are nonetheless able to lead rich, enjoyable lives. 

 

Since Rowe and Kahn’s original work appeared, the gerontologic literature has discussed “active aging” (to avoid the invidious comparison between success and its opposite, presumably failure). It has talked about “productive aging,” “healthy aging,” “aging well,” or “a good old age.”  But these alternative formulations all stigmatize in much the same way as does “successful aging.” The opposite of active is inactive, of productive is unproductive; the opposite of healthy aging is sick aging and the opposite of aging well is aging poorly. The opposite of a good old age is a bad old age. It seems to me that another way of looking at all this is to distinguish between the steps you should take when you are young and healthy to maximize the likelihood that you will retain certain capacities in old age, on the one hand, and the way you should deal with old age once it has arrived, on the other. 


What people may aspire to, in addition to simply living longer, includes the ability to take care of yourself (physical function), the ability to think and reason (cognitive function), and (emotional function). But as they begin to become old, whether denoted by reaching eligibility for Medicare or suffering physical or cognitive decline or becoming afflicted with chronic diseases, they need to figure out how to make the best of their existing condition. Whether they become short of breath on exertion due to years of cigarette smoking or due to environmental exposures or due to idiopathic pulmonary fibrosis (idiopathic implying that nobody has a clue what causes this progressive, debilitating condition), they have to make decisions about how best to live their lives, given their limitations. And those decisions reflect their personal preferences (what matters most to the individual), their circumstances (their financial, physical, and social situation), as well as what they aspire to for whatever time they have left.

 

In light of these distinct considerations—1) planning for the distant future, 2) planning for the near future, or 3) making the most of the current reality—I will offer my personal thoughts on turning 70. These are not prescriptions for other people; they are a description of my thought process, which may serve as an illustration of the kind of process others may wish to go through.

 

I start with the current reality. I am blessed with good health, which I attribute at least as much to genes and luck as to virtuous past behavior in the realms of exercise and nutrition. I am also fortunate to be financially comfortable enough that I do not need to work. At age 70, I find that I for the most part accept myself as I am, which doesn’t mean I cannot change (either for better or for worse) but rather that I feel I can focus on what I derive satisfaction from doing, not from what I feel I ought to do. That means spending time with my husband, who after 49 years of marriage remains my best friend. It means spending time with my 95-year-old mother and with my three sons, who have become fine and interesting adults. It involves trying to make sense of the world, which I often try to do by reading broadly about about health and medicine, incorporating what I learn from the realms of history, politics, science, sociology, and other disciplines to shed light on current problems. While I will engage in activities that I find meaningful, I will avoid activities that are stressful or create conflict. That has meant giving up seeing patients, which used to make me feel useful and even important, but which increasingly became burdensome as medicine became bureaucratic, patients became litigious, and disease remained as intractable as ever. I also want to devote more time to arguably purely selfish activities such as exploring the worlds of novels and of nature.

 

When I plan for the near future, say the next five to ten years, maybe longer if I’m lucky, I think of this as investing. Not in the stock market or the bond market, though insuring there will be sufficient retirement money to live comfortably is certainly important, but rather in my physical health and physical functioning. This is where exercise comes in, both aerobic exercise to guard against cardiovascular disease and strength training to remain nimble. Strength will be essential to enable me to continue to climb stairs and lift my new granddaughter and any other grandchildren who may come along. I also need to invest in building and deepening friendships, since I am persuaded that over the long run, the best bulwark against depression will be a strong social network. Finally, I want to continue to find ways to be engaged with the world, not just through friends and family. For me, that means remaining intellectually engaged. 

 

As to planning for the distant future—it’s too late for that. Truly long-range planning involves decisions about diet and exercise when you’re in your 20s and 30s; it entails deciding early on not to smoke; it means getting an education (education decreases but by no means eliminates the chance of developing dementia in later life).

 

As I enter a new phase of life—which feels more like a new stage because I recently became a grandmother, not because I had a birthday—I am going to make a conscious effort to develop new interests and new activities. Unlike Jane Brody, who advocates doing whatever you are passionate about as long as you can in large measure, I suspect, because she herself continues to be passionate about the same things she has always loved, I find that my enthusiasm for clinical medicine waned, as did my excitement about other aspects of geriatrics. I want to move more in the direction of reading, thinking, and ultimately writing about the history of medicine, and how that can help shape contemporary health policy. Recognizing that interests change over the life course, I gave up the practice of medicine. I’m not quite ready to let go of this blog, but I will write when there is a topic relevant to “life in the end zone” about which I feel strongly. I’m no longer going to peruse the New England Journal of Medicine and JAMA weekly for new developments that I might write about as I increasingly feel that what is published in medical journals no longer excites me the way it once did. I will still read Health Affairs and I’m expanding my horizons to include the Bulletin of the History of Medicine. I expect that my eagerness to blog will wax and wane. I hope you will bear with me as I begin to think about the end zone in a new and very personal way. 




April 05, 2021

Covid Cathy Bites the Dust

Now that just under half of older people have been fully vaccinated against Covid-19 and only about a quarter have not received any vaccinations at all,  the burning question is, what can vaccinated people do safely? 

 

The answer comes in two parts: what can vaccinated people do that does not jeopardize their own health and what can they do without risking harming others? The CDC has weighed in on this, focusing principally on the first issue, safety of the individual. Their guidance includes the recommendations that those who are fully immunized (who are at least two weeks out from their second shot) can visit other fully immunized people indoors without masking or social distancing and that they can travel without self-quarantining upon arriving at or returning from their destination.

 

To answer the second question, the public health concern, we need to know whether a vaccinated individual can be infected with Covid-19, remain asymptomatic, and transmit the disease to an unvaccinated person. Physicians have been concerned that while the antibody response to vaccination is highly effective in squelching the virus in the lungs, what’s not clear is whether it’s also effective in killing the SARS-Cov2 virus in the nasal passages. If so, vaccinated individuals could indeed be surreptitious sources of disease, like the notorious Mary Mallon, who was an asymptomatic carrier of the bacteria causing typhoid fever, salmonella typhi. Could asymptomatic Covid carriers act like “Typhoid Mary,” perhaps earning the nickname Covid Cathy? At last, we have very reassuring data addressing this issue.

 

The current issue of MMWR, the weekly journal published by the CDC, reports on the experience of just under 4000 people during the period mid-December and mid-March, 2479 of whom received two shots of either the Pfizer or Moderna vaccines and 989 controls who remained unvaccinated. They also report on 477 people who received one dose, but for simplicity, I will ignore these partially immunized individuals. The investigators leading this small study took one crucial step that has previously been largely lacking: they tested all the participants weekly using the gold standard polymerase chain reaction (PCR) test for the SARS-Cov2 virus—whether or not they had been vaccinated and whether or not they reported symptoms. What did they find?

 

The outcomes are reported based on “person-days” since the group who were vaccinated got their shots at varying times and therefore differed in the number of days they could have become infected. They found that among the fully immunized, the number of new positive tests/1000-person-days was 0.04 whereas among the unvaccinated, it was 1.38. The bottom line: once you are fully immunized, you are far less likely to test positive for Covid-19 than if you have received no vaccinations.

 

The study also found that only 23 percent of the people who did develop an infection got sick enough to see a physician, only two people were hospitalized, and no one died. 

 

Until this admittedly small but carefully conducted study appeared, it seemed to me that while vaccinated people could feel personally quite safe, they had to exercise caution in the interest of public health. It wasn’t really true that vaccinated people could socialize indoors with other vaccinated people—until the issue of Covid Cathy was resolved, they had to be worried about about any unvaccinated household contacts their friends might have, lest an asymptomatic carrier inadvertently transmit the virus to a friend, who while also asymptomatic, manages to give the virus to an unvaccinated household member. Now it increasingly looks as though this theoretical concern is not, in practice, of great consequence. 

 

Just because fully vaccinated individuals are reasonably safe today doesn’t mean they will necessarily remain safe tomorrow. Vaccine effectiveness is calculated based on how much less likely a vaccinated person is to get the disease than an unvaccinated one. But if the disease is running rampant in the surrounding community, that is, if it is quite common among the unvaccinated, then while the relative risk of the vaccinated will be unchanged, the absolute risk will go up. And if new variants appear against which the vaccines offer only limited protection, then the relative risk itself will be affected. 

 

So, keep an ear to the ground—monitor how common the virus is in the community where you live and pay attention to the type and pervasiveness of viral variants. If the situation is stable, enjoy your freedom.

March 04, 2021

How I Taught My 95-Year-Old Mother to Make and Receive Video Calls--Most of the Time

My 95-year-old mother has been using a computer for email since our then teenage son arranged to gift her his old computer so he could get a new one. That was 25 years ago. But like most people in her age cohort, she has never been comfortable with the technology and has trouble learning anything new related to the computer. The difficulty has gotten worse over time along with her memory. But when Covid hit and visits to the independent living complex where she lives were restricted and then eliminated, the limitations of a landline telephone became all too evident. If my mother could make and/or receive video calls, she could communicate with me, with her three grandsons in California, and with friends. But using the video technology proved to be an endless source of frustration. We tried FaceTime, we tried Skype, we tried Zoom. Nothing worked. 


Now, after months of trial and error and refining the approach, I’m pleased to report that my mother can receive—and sometimes initiate—FaceTime calls. I’m so pleased that I’m going to use this blog post to describe in as much detail as I can recall every step necessary to accomplish this feat, suspecting as I do that others may find themselves in a similar predicament.

                                                Happy geriatric iPad user 
                                                (not my mother)

Step 1: Choose an appropriate device. I purchased my mother a new 10.2 inch, 32GB iPad. It’s portable, so she can use it while sitting in her favorite recliner. The screen is big enough so that people’s faces appear almost life-size and photographs are easy to see. In principle, Apple products are user-friendly, though as it turned out, my mother is a genius at outwitting the human-computer interface gurus at Apple by coming up with ways to make the system fail. Nonetheless, I think the iPad was probably as good a choice as any and better than some. The rest of the steps below apply primarily to an iPad.


Step 2: Obtain a cover that automatically turns the device off when it is closed and turns the device on when it is opened. Turning the iPad on manually was an unnecessary obstacle.


Step 3: Disable password protection for turning the device on. This may be a bit risky, but my mother was having trouble remembering her password. I “enrolled” her in touch ID, but she usually managed to put her finger in not quite the right place, so it did not work reliably. Nothing is more frustrating than being unable to even turn the thing on.


Step 4: Go to Settings, Accessibility, Assistive Touch. This setting allows my mother to use the iPad even though she has poor fine motor control and touches the screen erratically.


Step 5: Label the home button. I stuck an arrow on either side of the home button to help my mother find it. The device is designed with a very slight indentation signaling the home button, so slight that it’s hard for 95-year-old eyes to see. ➡️ ⏺ ⬅️


Step 6: Make sure Siri is disabled. I initially thought it would be easiest if my mother used Siri to make calls, simply saying “hey Siri, call Muriel Facetime video.” Wrong. She would leave out “FaceTime” or leave out “video” or forget to start with “hey Siri.” She felt compelled to speak in grammatically correct sentences, as though Siri would understand her better that way. When I left Siri enabled, just in case things changed, I found that my mother would sometimes hold the home button down too long and inadvertently invoke Siri, who would helpfully inquire “may I help you?” Having her device suddenly speak really rattled my mother.


Step 7: Put only the most essential icons in the dock. For my mother, this includes the icon for her email, Safari, and for FaceTime video. I’ve recently added the photos icon.


Step 8: Declutter the screen by putting as many of the obligatory icons, the ones you can’t get rid of, on the next screen, not the screen that is opened when the device turns on.


Step 9: Put the handful of phone numbers (with associated names) that are most likely to be used in the FaceTime contacts screen. This way, when my mother taps on the video icon, she will see 4 or 5 names and can choose which one she wants to call. Sometimes she taps on the wrong spot and calls the wrong person, but at least she’s not accidentally going to call Social Security or the Boston Globe, just a different family member from the person she intended.


Step 10: Practice! When visiting my mother, I would get her settled in her recliner with the iPad and call her from another room. For a while she had trouble with the command “slide to answer.” I finally figured out that she was carefully sliding her finger along the words “slide to answer” and assiduously avoiding the green virtual button to the left of the words. Unless she accidentally touched the button, she failed to answer the call. Now I regularly remind her that she needs to slide the button and it works like a charm. Another aspect of practicing is using the system regularly. At one point, my mother was doing great and then we didn’t make any video calls for a few days, by which time she had forgotten about sliding the button rather than the words. Making or receiving a call once a day is probably a good idea.


Sounds simple, doesn’t it? Since it literally took me months to figure this out, I thought I’d pass along what I learned, in case these steps can help someone else.

 

 

February 26, 2021

Pfizer in Practice

This week brought a medical article worth discussing: the New England Journal of Medicine published the results of a study of the efficacy of the Pfizer SARS-CoV-2 vaccine in the real world. The article provides compelling evidence that the vaccine works extremely well.

The data come from Israel, which has been doing a superior job of vaccinating its citizens. As of a week ago, two-thirds of the currently eligible population in Israel had gotten both of the recommended doses (individuals under age 16 and those who have had Covid-19 are not eligible). In Israel, health insurance is mandatory for all permanent residents; they must join one of four healthcare organizations called “funds.” The new study reports data from Israel’s largest health organization (Clalit Health Services) and includes information on a stunning 1.2 million people.

The study’s authors, led by Dr. Noa Dagan, used Clalit's integrated electronic medical record to capture health data for 596,618 people who received both doses of the Pfizer vaccine between December 20, 2020 and February 1, 2021. They then matched them, based on demographic and clinical characteristics, with another group of identical size who had not received any vaccine. Next, they looked at five different outcomes: documented Covid-19 infection; symptomatic Covid-19 infection, Covid-related hospitalization, Covid-related severe illness, and Covid-related deaths. Because the sample was so large, they were also able to collect extensive information about a number of interesting subgroups defined by age or specific co-existing health conditions such as cancer or diabetes.

The article includes an enormous amount of intriguing data. The most exciting results, from my perspective, address outcomes a week or more after receiving the second dose of the vaccine. At that point, the vaccine conferred 94% protection against symptomatic Covid-19 (95 percent confidence interval 87-98), 87 percent protection against Covid-related hospitalization (CI 55-100), and 92 percent protection against severe Covid (CI 70-100).  The efficacy in people over 70 was identical to those in younger individuals, and the rate in people with one chronic health condition such as diabetes was only slightly lower than in people without the condition. 

These numbers strongly resemble the results that Pfizer and BioNTech reported to the FDA in their application for emergency approval.  But, as the study authors point out, Pfizer drew its conclusions based on 44,000 people; the Israeli study is based on 1.2 million people. As a result, when Pfizer calculated the efficacy against severe Covid-19, they drew on a total of 10 cases (one of whom had been vaccinated and 9 of whom had not been); when the Israelis calculated the risk of severe Covid, their estimate was based on 229 cases, vastly increasing the credibility and certainty of the calculation. Moreover, Pfizer’s data was based on the somewhat artificial conditions of a clinical trial: for example, the subjects were all highly motivated to optimize their health and may have regularly worn masks and practiced social distancing; the Israeli study drew on real life experience, in which participants’ behavior reflected community norms.

The new study, like all studies, has its limitations. It excluded people living in nursing homes and medical personnel working on Covid units in the country’s hospitals, arguing that the rate of the disease in their particular communities, i.e. the nursing home or the Covid ward, was highly atypical. The study was performed during a period when the South African variant was very rare in Israel so we cannot draw conclusions about the efficacy of the vaccine against this strain. The information on the ability of the vaccine to prevent Covid-related deaths is limited because of the short follow-up period: there were nine Covid deaths in the fully vaccinated and 32 deaths in the unvaccinated group, but these numbers might change when more time elapses. The data on deaths may also be difficult to generalize as Israel has an unusually low case fatality ratio: in Israel, according to Johns Hopkins' "Our World in Data," is currently 0.7 percent whereas in the U.S. it is 1.8 percent.

Some of the study’s greatest strengths are also potential weaknesses: the “real world” nature of the investigation means it is an observational study rather than a randomized controlled trial, raising the possibility that the differences in outcomes between the vaccinated and the unvaccinated were related to some factor other than their vaccination status. Despite these limitations, the study provides very encouraging information.

The fact that the Israelis could carry out their study sends another message over and beyond the efficacy of the Pfizer BioNTech vaccine. The study could only be conducted because Israel did a good job acquiring and distributing vaccine. Early on, the country developed mass vaccination sites. Since everyone is enrolled in a health plan and the plans all have electronic records, there was no need to waste as much time on bureaucracy as we do in the U.S, where more time is spent filling out forms than on administering the shot. The study could only be conducted because of Israel’s electronic health records, which assured that information about who got what dose when, and the age, sex, and chronic medical conditions of each individual was digitally recorded. Finally, the entire rollout was centrally coordinated, assuring efficiency and consistency: from the outset of the pandemic, the Israeli Ministry of Health collected Covid-related data from all four health plans, negotiated to purchase vaccine from Pfizer, and organized distribution. The good news reported in the NEJM article is a result both of the biological properties of an mRNA vaccine that was designed in record time to deal with an international health crisis of enormous proportions, and of the characteristics of a health care delivery system that can actually deliver.

February 21, 2021

The Next Big One

              As new cases of Covid-19 fall throughout the world but the US approaches 500,000 deaths from Covid-19 and the world nears 2.5 million deaths, it is time to start planning for the next pandemic. 

               We have known since the 1918 influenza pandemic, which killed upwards of 50 million people world-wide, that it’s not a question of if, but rather of when. Moreover, recent decades have seen the emergence of several new and terrifying diseases. These diseases have principally been caused by viruses, viruses that jumped species. They moved from their usual host, say a civet or a bat, into people for one of several reasons: climate change may have destroyed their hosts’ usual habitat, forcing them to find a new home where they came into greater contact with humans; alternatively, humans encroached on the hosts’ habitat by clearing forest or planting a crop that deprived the host of its usual food source, again leading the host to relocate; or humans may have developed a taste for certain types of wild animal, bringing the two species into unaccustomed contact and thus facilitating viral transmission.

              As a result of these factors, we have had Zika, SARS, MERS, avian influenza and now Covid-19 in the twenty-first century, and Ebola, Marburg hemorrhagic fever, and HIV in the last part of the twentieth century. These are only the best-known of “zoonoses.” Today, 75 percent of new infectious diseases are zoonotic in origin and their numbers have been rising steadily. 

            The good news is that we know a great deal about how to go about preventing outbreaks, detecting them early, and responding if they nonetheless occur. The bad news is that the world in general and the U.S. in particular have a poor track record of implementing the necessary strategies. Allocating scarce resources now to help alleviate problems that will develop at some unspecified time in the future has proved to be a hard sell. 

                The irony is that we in the U.S., as in many other countries, spend an enormous amount of money on our military. We have accepted the need to devote a large fraction of our budget to the armed forces and to equipment including both “conventional” and nuclear weapons. We have not yet acknowledged that the far greater threat to our national security and our well-being is from lowly viruses, strange biological entities that are not strictly speaking alive since they cannot survive outside a host organism, not from invading armies. 

            The current US budget consists of just under $3 trillion on “mandatory spending,” which includes Social Security, Medicare, and Medicaid; and another nearly $1.5 trillion on “discretionary spending,” over half of which is for military spending, including the VA and Homeland Security as well as the armed forces. The base budget for the Department of Defense is $636 billion.

             By comparison, the CDC (Centers for Disease Control), the site for most of the U.S. epidemic preparedness activities, has a total budget of $6.6 billion, of which $509 million is allocated to “Emerging and Zoonotic Infectious Diseases.” Other disaster preparedness activities are financed through various departments, including Homeland Security, which is part of the military. But as a very rough approximation, it is not far-fetched to say that the core budget for potential epidemics is $509 million compared to the core budget for the military of $636 billion, or .08 percent.  This comparison reveals an enormous imbalance between spending on the military and on epidemic preparedness, with too much to fight armed invasions and not nearly enough to combat microbial enemies.

            If we are to spend more on epidemics—and, arguably, less on bombs and fighter planes—what should we spend it on? A basic framework was outlined at a symposium called “Building Interdisciplinary Bridges to Health in a Globalized World,” organized by the Wildlife Conservation Society in 2004. The symposium called for an international, interdisciplinary approach to preventing disease, or “One Health, One World.” It articulated its views in a document called the Manhattan Principles which laid the foundation for what would become an international movement. The Manhattan Principles is built on  the recognition that modern epidemics stem from the inter-connections between humans, domestic animals, and wildlife, and that these interactions arise either directly from human behavior (eg agricultural practices, clear cutting forests, and eating wildlife), or indirectly, mediated by climate change that is in turn due to human behavior. Since the problem is fundamentally multidisciplinary, its solution must likewise be multidisciplinary. And since the modern world is interconnected, the solution must be international, involving sharing information.

            An implementation framework was drawn up in 2008 by a group consisting of representatives from UNICEF, WHO, the World Bank among others. Entitled “A Strategic Framework for Reducing Risks of Infectious Diseases at the Animal-Human-Ecosystems Interface,” it argued for the development of an international system of disease surveillance drawing on multidisciplinary expertise (to include veterinarians, physicians, wildlife specialists, and ecologists). In addition, it sought to help build robust public health systems across the globe and to promote good communication between those systems. Finally, it advocated support for strategic research, to be shared internationally. 

            The One Health approach was adopted by the CDC in 2009, which housed it within its National Center for Emerging and Zoonotic Infectious Diseases. It was formally endorsed by the UN, the World Bank, and the EU in 2010. More recently, the World Bank came up with a revised operational framework to fight EIDS as a means of fulfilling its mission to promote prosperity and decrease poverty.

            Our response to future epidemics, when they occur, will hinge on more than international and multidisciplinary collaboration. Scientific developments are likely to have a major impact when future EIDs arise. The new technique of vaccine design using mRNA is vastly accelerating the development of effective vaccines, the most powerful preventive tool available. Work on anti-viral medications is ongoing and could revolutionize treatment of viral diseases much as antibiotics revolutionized the treatment of bacterial diseases. Currently, the only virus for which there is effective treatment is HIV, and that treatment (which took years to develop) involves a multi-drug regimen that converts HIV into a chronic disease but rarely eradicating the infection. 

            We also need to strengthen the public health infrastructure in the U.S. Poor coordination, insufficient manpower, and inadequate communication to the public have afflicted domestic public health departments for years. WHO and the World Bank have focused on shoring up public health in much of the world but assumed that the richest countries would serve as models of success. 

            The One World framework could itself be expanded to address climate and the environment more expansively, but the basic formulation is sound. As Andrew Cunningham, Peter Daszak, and James Wood argue in their 2017 article, “One Health: Emerging Infectious Diseases and Wildlife: Two Decades of Progress?” little has been done at the policy level to address what remain major threats to health and well-being, as Covid-19 attests. It’s time to adjust our national priorities and focus on what counts. 

 

 

January 11, 2021

The Home Stretch

For Americans over age 65, the Covid-19 vaccine really is coming soon. States have varying policies on prioritizing distribution of the vaccine, with some states already giving it to those older than 65 and others planning to get to the over 75 group very soon and the 65-74-year-olds shortly thereafter. In all cases, the expectation is that by April, all older Americans will have had the opportunity to be vaccinated. 

If you are reading this post, you have made it this far—so my message today is don’t blow it now by throwing caution to the winds. The virus is striking more people each day than ever before, and despite the progress in treatment, more people are hospitalized and more people are dying than at any time in the past year. 




The US also has the dubious distinction of being number one in the world in terms of cumulative mortality from Covid-19.  

Tired as we all are of masks and social distancing and of just plain staying home, these are the only strategies we have until we are vaccinated—and even then, we’ll need to wait until most of the population has been vaccinated before we can relax. A more infectious strain, isolated in the UK, is here in the US. It may be far more widespread than we know since public health officials are not routinely testing for it. Just because we haven’t found it doesn’t mean it doesn’t exist: it just means we’re not looking for it. 

The implication of all this is that it would be prudent not merely to remain careful, but to increase your vigilance. Writing in the medical news periodical, STAT, several physicians and an engineer argue that we should wear high filtration masks such as the N-95. We should take their proposal seriously. While N-95 masks are primarily restricted to health care workers, KN-95 masks, which are in many cases equivalent, are available from Amazon, some local pharmacies, and a variety of other on-line sources. Most of these have not been tested for effectiveness or reliability by American government regulators, but many have been subjecting to assessment by one or more international agencies. The CDC has made available a list of many KN95 masks and the results of the assessments. 

My recommendation is to start wearing one of the KN-95 masks on this list, choosing one that has a minimum filtration efficiency of at least 95 percent. Wear it indoors in any public space. Do not socialize indoors except with members of your household. Do not take unnecessary risks and don’t let down your guard! 

January 01, 2021

Looking Forward

            Once the 1918-1919 influenza pandemic finally came to an end—after killing somewhere between 50 and 100 million people worldwide—Americans did their best to forget about it. Later tragedies such as AIDS and 9/11 figured prominently in much American fiction, but influenza was seemingly forgotten by American writers: Katherine Anne Porter’s short story, “Pale Horse, Pale Rider” and William Maxwell’s novella, “They Came Like Swallows,” are rare exceptions. Historians and journalists writing about the 1918 flu have hypothesized that the pain and suffering inflicted by the flu paled by comparison with that attributable to World War I, which came to an end at the same time, even though ten times more Americans died of the flu than died in combat. Or perhaps Americans were so optimistic about scientific medicine, which was just coming into its own in the twentieth century, that they chose to ignore medicine’s great failure, its inability to diagnose, treat, prevent, or cure influenza. Maybe Americans simply repressed this traumatic episode that killed people in the prime of life, leaving families without a means of support and children without a mother or father. Will the Covid-19 pandemic similarly be forgotten, or will it have a profound and enduring effect on us as individuals and on us as a society?

            The pundits are already speculating about the long-lasting effects of the pandemic on the real estate market and on the work place, on professional conferences and the movie industry. But what I would like to address is the life lessons we should take away from this devastating and unexpected year. The first is that our lives are tenuous. We in the developed world have come to expect a long healthy life, especially if we are white and middle class. Life expectancy at birth in the US is just under 79 years; if you make it to age 65, you can expect to live another 20 years. Covid-19 showed us that we should not take those years for granted: while 80 percent of the Covid deaths have been in people aged 65 or older, that means that 20 percent have been in people under 65. As of the end of December, 2020, 346,000 Americans had died from the disease, which translates to 69,000 younger people. There’s nothing like awareness of our own mortality to concentrate the mind and encourage us to live life well and to the fullest. This is the first lesson and the one we are perhaps most likely to forget.

            The second lesson is that what matters most to us as human beings is our relationships with other people. That’s what made “social distancing” so painful; it’s why eliminating family visits to nursing homes was so devastating; it’s why Zoom, FaceTime, and other video chat programs have been such a lifesaver. We need to cultivate our friendships, to nourish them, to work to improve them. The pandemic made us believe that other people are the enemy, which runs counter to our essence as social creatures.

            The third lesson that I want to emphasize is of a different sort: it is that to make decisions about most anything important and certainly to make medical decisions, we need to understand something about risk. How to behave during the epidemic was all about how to evaluate risk, how to think about risk. Just because most people who don’t wear masks and who go to group gatherings won’t get sick doesn’t mean that these are safe activities. It means that you markedly increase the chance that you will contract the virus if you go around without a mask or attend a group meeting. And understanding risk is more complicated still: how much you increase your risk depends on how widespread the virus is in the surrounding community. If very few people in the vicinity of where you live are sick, then your likelihood of getting the disease is low, even if you fail to take precautions. But as the virus begins to circulate more widely, then precisely the same behavior pattern that was only slightly unsafe before will become far more dangerous. 

            Understanding risk is tricky because the epidemiological measures designed to protect individuals, whether wearing a mask, practicing social distancing, or getting vaccinated, are not perfectly effective. Some people who wear a mask will nonetheless contract the virus; ditto for people who stay six feet away from others. Individuals who received either the Pfizer or Moderna vaccination in the clinical trials were one-twentieth as likely to get sick as those who received a placebo. But that means that just how safe you can feel if you are vaccinated  (even if the effectiveness holds up in a much larger population than was tested in the trials) also depends on how widespread the virus is: while vaccination lowers your relative risk of getting sick, if the number of infectious people in the community suddenly increases, say by a factor of ten, your chance of getting the disease also goes up by a factor of ten, even if you've been vaccinated. Grasping the concept of risk is essential—not just to dealing with an infectious disease, but also to deciding whether to undergo screening for prostate cancer, whether to take medication for borderline high blood pressure, and whether to invest in the stock market. 

           Americans, along with people across most of the globe, have lost much from our encounter with the corona virus. We have also gained something: an appreciation for life’s fragility, a recognition of the importance of relationships, and a deeper understanding of risk. It is up to us to remember, both those we have lost and what we have learned. 

December 07, 2020

Dateline: Pearl Harbor

Exactly 79 years ago today, Japanese planes bombed Pearl Harbor, an American naval base on Oahu, Hawaii, catapulting the U.S. into World War II. "A day which will live in infamy," President Franklin Roosevelt would call it--a day which lives on in the memory of the oldest Americans (though not, evidently, of the NY Times, which did not mention it in today's newspaper). The attack, which destroyed more than 300 planes and killed or wounded 3400 Americans, dealt a devastating blow to America’s sense of invulnerability and to our isolationist tendencies. It was also the last time the armed forces of a foreign nation would penetrate the American homeland. And yet, deep into the 21st century, the U.S. continues to place disproportionate weight on armed invasion as the major threat to the security of all Americans, young and old.

As the Covid-19 pandemic, the devastating wild fires on the west coast, and the unprecedented number of named storms this season demonstrate, America must address several other crucially important problems if its citizens are to remain safe and its democracy strong. Epidemics and climate change are two of the principal non-military threats; cyber-attacks and attacks on science are two additional substantial threats. 

Why do these non-traditional forms of attack constitute a threat to the national security? Epidemics have the potential to harm or kill tens of thousands, hundreds of thousands, or even millions of Americans; in addition, they can disrupt the economy (either because sick people cannot work or as society limits economic activity to protect health); and they can damage or destroy fundamental institutions such as the health care system by overwhelming its capacity. Climate change, by causing sea level rise, risks destroying coastal property or submerging entire cities; by contributing to natural disasters such as mudslides and wild fires, climate change endangers life and property. Rising maximum temperatures may make parts of the country uninhabitable or cause death from hyperthermia; they might destroy industries such as cod or lobster fishing as entire animal species migrate north in search of cooler waters. 

Cyber-attacks, whether carried out by state actors, by international terrorists, or by domestic criminals, can disrupt the financial system, the energy grid, our elections, or other fundamental institutions essential to the health and safety of Americans. Attacks on science constitute a fourth non-traditional threat, one that is just coming to be recognized as endangering both progress and our democracy: progress because a citizenry that rejects science will reject legislators who support science, resulting in diminished funding of the research essential for improvements in health and security; democracy because citizens cannot tell truth from falsehood will not have the information necessary to vote in their best interest. Undermining science will, in addition, exacerbate climate change and increase the likelihood of pandemics.

The idea that threats might not come from a foreign state actor but rather from microorganisms (in the case of a pandemic), from the anthropogenic production of greenhouse gases (in the case of climate change), from a computer hacker (in the case of cyber-attacks), or from lies and propaganda distributed via social media (in the case of the attack on science and, more generally, on truth, knowledge and expertise) represents a fundamental change in the way we need to think about national security. And just as the terrorist attacks of 9/11/2001 led to the creation of the Department of Homeland Security, so too should the current pandemic push us to reconsider the effort we devote to fending off other non-traditional types of attack. 

Consider the case of microbial threats. The idea of investing in pandemic preparedness is not new: the danger of pandemics and the importance of a coherent response strategy has been acknowledged by public health professionals since the influenza epidemic of 1918-1920. Each of the subsequent pandemics of the 20th century (Asian flu in 1957 and AIDS beginning in 1981), as well as the first pandemics of the 21st century (SARS in 2003, Swine Flu in 2009, and Ebola in 2014), brought renewed interest in both prevention and mitigation. Increased understanding of the origins of these outbreaks has led to a recognition of the importance of surveillance: we now realize that all the major pandemics have been zoonoses, they have arisen from viruses that jumped from one species, such as bats, to another species, humans, because of disruptions in the natural habitat of the original host. Furthermore, realization that global interconnectedness promotes rapid spread of the most readily transmissible organisms has resulted in an appreciation of the importance of international cooperation in combating pandemics.

Such recognition and realization emerged from thoughtful and comprehensive reports such as the workshop on "ethical and legal considerations in mitigating pandemic disease" sponsored by the Institute of Medicine. Its proceedings were published in 2007. This was followed in 2016 by a chilling report from the National Academy of Medicine, “The Neglected Dimension of Global Security: A Framework to Counter Infectious Disease Crises,” that made explicit the connection between national security and epidemics.

These documents did not just collect dust in government archives; their conclusions were, to a limited extent, translated into US public policy. Beginning with President Clinton, each presidential administration has put forward a new or revised pandemic preparedness plan. Congress authorized the establishment of a Global Emerging Infections Surveillance program within the Department of Defense in 1997, a program intended to improve surveillance, to foster prevention, and to plan for a response to potential new microbial threats. George W. Bush had his “Biodefense for the 21st Century” plan, precipitated by the anthrax scare, though this focused principally on bioterrorism, the deliberate dissemination of disease-causing organisms by state actors or individual terrorists. Obama had two: the “National Strategy for Countering Biological Threats” in 2009 and the “National Strategy for Bio-Surveillance” in 2012. Trump had his “National Biodefense Strategy” in 2018, which addressed naturally occurring, deliberate, and accidental biological threats, and theoretically centralized the federal response in the Department of Health and Human Services. 

These policies sound good on paper. But implementation, coordination, and funding have lagged. For example, the Centers for Disease Control budget allocation for prevention of zoonotic diseases in 2020 was $636 million out of a budget of $6.5 billion; Trump’s proposed 2021 budget asks for $550 million. The total Department of Defense allocation for FY 2021, by contrast, is $933 billion.

More generally, both the current (FY2020) and proposed (FY2021) federal budgets include support for combating pandemics and cyber-attacks, but do little to support combating climate change (the phrase is nowhere to be found) and nothing to defend against attacks on truth or on science. Even when the threats are acknowledged, the programs responsible for combating them are disseminated through multiple disparate agencies, are poorly coordinated, and receive only modest funding. 

Pearl Harbor Day should serve as a reminder of how threats to national security have changed in the three quarters of a century since Japanese bombers crossed the Pacific and entered American airspace. For starters, we should have a cabinet level department to take these new threats rather than embedding them into the Department of Defense, which has been structured to focus on the military. Perhaps we should simply reconfigure the Homeland Security Department, which no longer focuses on the prevention of terrorist attacks, the rationale for its establishment, but rather devotes its efforts to the enforcement of immigration policies. Immigration is not a threat to national security; but pandemics, climate change, cyber warfare, and the attacks on truth in general and on science in particular pose a real and present danger.

 

 

 

November 17, 2020

Now Hear This

On November 9, we learned that the preliminary data from the Pfizer/BioNTech COVID-19 vaccine trial are very promising; exactly one week later, we got similarly good news from the ModernaTX/NIH study.  What do the Moderna data show and how do they compare with the Pfizer data?

Moderna began enrolling patients last summer and has recruited 30,000 volunteers, half of whom received two doses of vaccine and half of whom got placebo, in both cases at 30-day intervals.  

The subjects, adults over the age of 18, were divided into 3 groups: people age 65 or older; people under 65 with known risk factors for coronavirus; and people under age 65 with no known risk factors. The principal outcomes that the researchers are tracking are the ability of the vaccine to safely prevent symptomatic COVID-19 infection and the capacity of the vaccine to stimulate antibody production in recipients. In addition, the researchers are looking at whether the vaccine can prevent severe COVID-19 infections and whether it can prevent asymptomatic infection (as measured by markers for COVID indicating current or previous infection despite the absence of symptoms).

The newly reported results are based on the 95 enrolled subjects who have thus far been diagnosed with COVID-19. Being diagnosed with COVID-19, according to the definition in the study, means having a positive PCR (polymerase chain reaction) nasal swab after developing symptoms consistent with the disease. What we know is that of these 95 individuals, 5 had received active vaccine and 90 had received placebo. We also know that 20 of the 95 people with the illness were over age 65 and that 11 people developed severe disease, none of whom had been vaccinated. While the specific numbers have not been reported, Moderna has asserted that the efficacy was the same among the different age groups as well as among various ethnic groups (or, more accurately, given the very small numbers of sick people, they were unable to detect any differences).

What we don’t know is the duration of the protective effect. We don’t yet know whether the vaccine prevented asymptomatic infection, although we should know something about its capacity to do so when the endpoint of the study is reached, namely when 151 enrolled individuals have been diagnosed with symptomatic disease. And we don’t know whether the vaccine is effective in children.So, how does the Moderna vaccine compare to the Pfizer vaccine 

They are both mRNA vaccines, a type of vaccine that has never been approved for human use. The efficacy rates reported thus far are extremely similar: from a statistical standpoint, the 95 percent efficacy quoted by Moderna is not any different from the 90 percent efficacy quoted by Pfizer, given the small number of sick patients.  

Both vaccines have to be kept cold to remain viable, but shipment and long-term storage of the Pfizer vaccine has to be at 70 degrees below zero Centigrade while long-term storage of the Moderna vaccine can be at 20 degrees below zero Centigrade; on arrival at your local drug store or physician’s office the Pfizer vaccine can be refrigerated at normal temperatures for up to 5 days while the Moderna vaccine can be refrigerated at normal temperatures for up to 30 days without losing potency. 

The Pfizer vaccine has been tested in children; the Moderna vaccine has not so we just don’t know whether it will work in this age group. Finally, the Pfizer vaccine is to be given as two doses separated by 3 weeks while the Moderna vaccine is given as two doses separated by 4 weeks; efficacy was tested by Pfizer beginning 1 week after the second dose and by Moderna beginning 2 weeks after the second dose. These differences may not reflect actual differences in the two vaccines, simply different protocols instituted for studying them. In sum, it looks as though the two agents are very similar except for differing refrigeration requirements. 

Quite apart from the biochemistry of these vaccine candidates and the data on their efficacy, what do we know about Pfizer and Moderna? 

Pfizer is the Goliath of pharmaceutical companies. As of March, 2020, it was the largest drug company in the world, as measured by revenue, with annual revenues of $51.75 billion. It has experience in producing vaccines and in recent times was responsible for the development of one of the major pneumonia vaccines. But Pfizer is also a leading offender among the major drug companies in unethical and illegal behavior. In 2009, it achieved notoriety for the largest settlement ever made by a drug company with the Department of Justice: It agreed to pay $2.3 billion for fraud involving the atypical antipsychotic drug Geodon and the painkillers Bextra and Lyrica. It would lose the distinction in 2012, when GlaxoSmithKline settled with the DOJ for $3 billion. 

Despite signing a “Corporate Integrity Agreement” in 2009, a quick internet search reveals that Pfizer continued to engage in bad behavior: in 2011, it paid $14.5 million for the illegal marketing of Detrol; in 2016, it paid $784.6 million to resolve a lawsuit involving Medicaid fraud; in 2018, Pfizer paid $23.85 million to resolve a suit over Medicare kickbacks. It’s worth noting that most of the big pharmaceutical companies have engaged in fraud, including such names as Johnson & Johnson, Eli Lilly, Abbott, Novartis, and Merck. They seem to regard playing fast and loose with the rules as part of doing business.

If Pfizer is the Goliath of the industry, Moderna is the David of the industry—or was until it went public in 2018, raising $604 million through the sale of its shares and gaining a valuation of $7.5 billion despite never having brought a product to market.

Moderna began as a small biotech startup in 2010 and has focused on mRNA vaccines since its inception. Questions have been raised about the integrity of the company in light of its culture of secrecy and the high-stress environment created by its CEO. 

Some have even wondered whether Moderna would be the next Theranos, the unicorn ultimately exposed as a fraud, a story detailed in the chilling account by WSJ investigative journalist John Carreyrou in “Bad Blood: Secrets and Lies in a Silicon Valley Startup.

Moderna has partnered with NIH (specifically the National Institute of Allergy and Infectious Diseases) in its COVID-19 vaccine project. Hopefully, the involvement of a highly reputable, not-for-profit, academically oriented organization has provided a layer of oversight to the drug company.

So far, the data from both the Moderna/NIH trial and the Pfizer/BioNTech trial look very auspicious (BioNTech, by the way, is a German company devoted to developing immunotherapies, principally as treatment for cancer; it has partnered with Pfizer for years in a thus far unsuccessful effort to produce an mRNA vaccine against influenza). Let’s hope that the record of American Pharma in general, and the questionable past behavior of both principal companies in particular, prove irrelevant to our health.