Boosters - Needed? When?

This week saw an announcement from the Biden administration that a 3rd Covid-19 vaccine shot would be recommended for everyone 8 months after their second mRNA (Pfizer or Moderna) shot. Is this a good idea? What does it mean for you?

Since antibodies gradually fade over time, most vaccines are given in multiple doses over an extended time. If you get hepatitis B immunization, you get 3 shots over 6 months. Most childhood vaccines are spread out over years. The current shingles vaccine is given as two shots, 2 to 6 months apart.

The mRNA vaccines were tested (and thus approved for use) using a relatively tight time frame, 3 or 4 weeks apart. I am sure this was because of the urgency of getting these vaccines tested and available. Indirect evidence from Britain, where the second shot was deliberately delayed to permit as many first shots as possible, suggests a longer interval gives even better protection.

Real world evidence shows that these vaccines are extremely effective, even against the Delta variant, with 80%+ prevention of infection and 90%+ prevention of hospitalization out to 6 months. The one group where evidence strongly suggests a third dose is needed are those with depressed immune systems, such as transplant patients.

A recent study found that among nursing home residents, who got the vaccine early, the protection gradually waned, falling as low as 53% 8 months after vaccination. Another, looking at New York residents, found that protection against infection dropped from 92 to 80%, though protection against hospitalization remained over 90%.

A very small recent study, done by Pfizer, found a marked increase in antibodies when a booster dose was given 8-9 months after the second original vaccine.

SO:

1.Yes, a booster is probably a good idea.

2.If you have a depressed immune system, you should get this as soon as possible.

3.If you are otherwise healthy, there is no need to panic and seek one out before you are due.



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Has the FDA lost its way?

The FDA failed the U.S. public by approving Biogen’s new Alzheimer’s drug against the recommendation of its expert advisory panel and its own statisticians. That event led me to explore whether this was an aberrancy or part of a pattern, and what I found disturbed me.

The FDA’s origins lie in the Food and Drugs Act, passed by Congress in 1906 and signed into law by President Teddy Roosevelt, which prohibited interstate commerce in misbranded and adulterated foods and medications. Much of the impetus for getting this bill enacted was the revelations by such “muckraking” journalists as Upton Sinclair, whose novel The Jungle exposed unsafe and unsanitary conditions in the meatpacking industry.

Probably the high point of the FDA was in 1961, when Canadian-born Dr. Frances Kelsey refused to allow the sale in the U.S. of thalidomide without further safety data, and her judgement was rewarded when the drug, widely prescribed in Europe for morning sickness, was found to cause serious birth defects.

This episode in turn led to passage of the Kefauver-Harris amendment to the Food and Drugs Act which required that all new drugs demonstrate “substantial evidence” of efficacy as well as safety. This is where the recent FDA decision failed to meet the intent of the law, but it is not the only time.

Under pressure from AIDS activists in the early 1980’s, the FDA developed an accelerated pathway to approve promising new drugs for otherwise poorly treated diseases, with the proviso that on-going studies be done to prove that the drugs fulfilled their promise. A study published this year in the British Medical Journal found that many drugs approved under this accelerated pathway stayed on the market for years or decades without the required studies being done and with major doubts about their efficacy persisting.

I am particularly concerned about the frequent approval of new cancer drugs, most with huge price tags and major side effects, based on “surrogate outcomes:” measures of changes in blood tests or imaging findings that might show the disease is responding, but which do not show meaningful results in terms of prolonging life.

The FDA is also responsible for regulating medical devices such as implants and pacemakers. Here too, as a ProPublica investigative report found, the FDA has often deferred to manufacturers and allowed dangerous products to stay on the market far too long.

How can these problems be improved?

First, as much as possible, the FDA, and the CDC, should be insulated from political pressure. The heads of these agencies should have terms that do not overlap with presidential terms and should be able to be removed only for malfeasance, so that they can make decisions based on science, not politics. Many public health decisions involve trade-offs but improving a president’s reelection odds should not be a factor when it comes to saving lives.

A much more “arms-length” relationship between the regulators at the FDA and the device and pharmaceutical industries must be enforced. No revolving door between agency and industry should color the regulators’ decision making.

The FDA should not be allowed to overrule the decisions of medical experts unless these decisions are close. If a vote is 6-5 with one abstention, there is room for the FDA to decide on approving a new drug based on their judgement. When there is a super majority vote, it should be respected.

Let us demand that the FDA uphold Dr. Kelsey’s standards.

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Do I need to wear a mask (AGAIN!)?

The headlines this morning were all about the CDC changing its guidelines about whether vaccinated people need to wear masks. In typically nuanced language, they tried to differentiate between those living in areas with high spread and low vaccination rates and those in areas with fewer cases and better vaccination uptake.

What should YOU do?

A few facts:

The Delta variant is now dominant. Nationally, over 80% of strains tested are Delta. Even in Massachusetts, which has one of the highest vaccination rates and lowest cases/population in the country, Delta now makes up over 50% of Covid cases.

Delta is not more deadly – hospitalizations and deaths from Delta are similar to those caused by the original strain.

Delta IS much more contagious. People infected with the Delta variant carry many more virus particles in their nose and upper airway, and thus are much more likely to transmit the virus to others. This is why case counts are rapidly rising in almost every state.

The m-RNA vaccines, in particular, are very good at protecting you from getting infected and even better at preventing serious illness and death from Delta, but they are not 100%. Even if you are vaccinated, you can catch COVID-19 and pass the virus to others.

So, my advice is:

Avoid travel to Florida and other hotbeds for now until they get their act together.

If you live in a state with low vaccination rates, I would wear a mask any time you are indoors with people you do not know are vaccinated and outdoors when you will be in crowds.

If you live in New England or another region with high vaccination rates, it gets more complicated. Life is never risk-free. Every time you get in a car, you are accepting some risk. At the same time, you do common sense things to lower the risk: you wear a seatbelt and you obey traffic laws.

What seems sensible is to wear a mask when you are indoors in crowded spaces: theatres, grocery stores, houses of worship. I would also wear one outdoors if it is a very crowded space where people are always close such as parades and stadiums. This will both reduce your risk and the risk that you could pick up a mild infection but pass the virus to others. It is thus particularly important if you have friends or relatives with poor immune systems.

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Delta dawns

The news media have been filled with stories about the delta variant of the coronavirus, some factual, some scary. What do you need to know?

First, it is a fact of life that many viruses constantly mutate. That is why you get a flu vaccine every fall: not because your immunity from last year has faded, but because the expected influenza virus will be different than the one that circulated last season. Some of the changes in the virus’ genes make them more dangerous to humans, some less. Some mutations make them less easily transmitted, some more. If a variant is more infectious and/or more easily transmitted from one person to another, it eventually becomes the dominant strain.

This appears to be happening in the U.S. with the delta variant. Luckily it does not seem to be more lethal than earlier strains, but it is more easily spread, and is rapidly becoming the most common form of the virus. Along with the appearance of the delta variant, we are seeing a recrudescence of COVID-19 infections. The lifting of restrictions and decreased mask use is almost certainly also playing a role.

I track the virus in Massachusetts and a month ago our average of new cases was down to 57 a day, and the percentage of Covid tests that were positive had fallen to 0.3%. This week, we are seeing 250 new cases daily and 1% of tests are coming back positive.

This is true across the country. The head of the CDC noted on July 16 that the number of new cases had risen 70% from the prior week. Along with rising cases, hospital admissions had gone up 36% and deaths 26%.

The natural immunity acquired after a mild case of COVID-19 does not seem nearly as effective against the delta variant as it is against to original virus strain. The good new is that the available vaccines do seem very effective, and if you are fully vaccinated, you are extremely unlikely to get seriously ill or die.

Virtually all the recent hospitalizations and deaths have been in unvaccinated people.

While being unvaccinated is clearly dangerous to those individuals, it is also dangerous to others. People who get infected are the source of new variants, and the unvaccinated serve as incubators to produce potentially more lethal variants. Lambda anyone? This new variant now rampant in South America is less susceptible to current vaccines.

If you have not been, PLEASE get vaccinated, for your sake and for ours.

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Vaccines and the Heart

There has been considerable discussion in the media and medical journals about possible heart damage in young males who received the m-RNA vaccines against COVID-19. While we do not yet know enough to make absolute pronouncements, we are learning quite a bit and can make some informed decisions.

Some facts:

1.Myocarditis, inflammation of the heart, occurs from many causes, including COVID-19 infection itself. Some 1% of athletes who had mild COVID infections had evidence of heart inflammation when carefully studied, though most of them had no symptoms.

2.The “normal” occurrence of myocarditis in the U.S is about 10 cases/100,000 people/year. Based on studies in Israel and the U.S. military, the incidence in young adults receiving 2 doses of the Pfizer or Moderna vaccines was several times higher than would be expected, albeit still rare. In the U.S. military, 23 cases were reported after 2.8 million does had been given. The CDC reported 196 cases among young adults, 16-24, when 27,000,000 vaccine doses had been given to this age group.

3.To date, most of the reported cases have occurred in adolescent or young adult males and almost all were soon (less than a week) after the second dose of vaccine.

4.Symptoms included chest pain, and most had some combination of elevated enzymes showing heart muscle damage, minor ECG abnormalities and abnormal heart scans. Virtually all the reported patients had mild illness, with good recovery in about 4 days with a variety of treatments or with no treatment.

The Advisory Committee on Immunization Practice has strongly advocated that the vaccines’ benefits for adolescent males exceed their risk, and this is probably true. The benefits of vaccination do outweigh the risk, even in this select group, but how vaccination is done can take the myocarditis risk into account.

One could argue that healthy young males might prefer to receive the J&J one-shot vaccine, in which this condition has not been reported. I would also argue that young males who have recovered from COVID-19 could be considered safely immune after a single rather than both doses of the m-RNA vaccine and thus avoid the second dose that seems to be the trigger.

Stay tuned. I am sure we will learn more.

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It is not all someone else's fault!

As regular readers of these posts know, I think that all parties in the U.S. healthcare “non-system” overcharge for what they do, and often under-deliver. While hospitals, insurance companies, the pharmaceutical industry and many doctors clearly contribute to our excess spending, the under-performance of the U.S. in health outcomes is largely not their fault.

Most public health experts agree that 75-80% of a nation’s health is the result of factors other than the quality of its hospitals and doctors. Things such as housing, travel, air and water quality and poverty are much more important to our life expectancy. Also outside of the control of the healthcare system are our personal behaviors.

This post was prompted by a recent study out of Michigan looking at the modifiable risk factors in patients found to have advanced coronary disease. We know that beyond age, major risk factors for coronary disease include cigarette smoking, hypertension, hyperlipidemia, diabetes and obesity. Almost all (95.5%) patients undergoing angioplasty had one or more of these risk factors, and half had three or more. Current smokers presented a full decade earlier than non-smokers and obese patients four years younger than those at normal weight with their advanced coronary disease.

These findings dovetailed nicely with a 2018 study in the journal Circulation. That study looked at five factors almost entirely in our control: a healthy diet, not smoking, modest or no alcohol use, regular aerobic exercise and keeping a healthy weight. Doing more of these things resulted in fewer cancers, fewer heart attacks and longer lives. They calculated that a 50 year old woman who did all five of these things right would live 14 years longer than a woman who did none; a 50 year old man who was 5/5 would live 12 years longer than one who did none.

So, get off that couch, put down the remote and the chips and get out there!

To quote William Shakespeare, "The fault, dear Brutus, is not in our stars, but in ourselves.."

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The FDA Fails

On June 7, the U.S. Food and Drug Administration (FDA) over-ruled the advice of its own expert advisory panel and approved for sale Biogen’s aducanumab, a manufactured monoclonal antibody that will be marketed as Aduhelm, for the treatment of Alzheimer’s disease (AD). Since then, at least three of its experts have resigned from their advisory roles in protest. The drug, which requires monthly IV infusion, will be priced at $56,000 per year.

The stock market certainly applauded the FDA decision: Biogen’s stock price rose 38% on the day of the announcement. The Alzheimer’s Disease Association took out a full page ad in the Wall Street Journal applauding this “breakthrough” approval. The response of the medical community has been much more muted, with a majority of experts who treat dementia urging caution in its adoption.

Why the sharp difference? Amyloid, an abnormal protein made of clumps of naturally occurring proteins, is a hallmark pathologic finding in the brain of patients with AD. Whether it causes AD or is simply a marker is unclear. A variety of similar drugs have been tested over the years and while many have reduced the amount of amyloid in the brain, none have produced any clinical benefit.

Biogen sponsored two trials of aducanumab and both were stopped by their steering committees because no benefit was seen. Biogen then reanalyzed one of the trials and did show some benefit. Despite the claim of “breakthrough,” even the benefit found by Biogen’s scientists was at best modest. The difference in a score of AD severity between treated and untreated patients was 0.39, on a scale of 0 to 18 – statistically significant according to Biogen but hardly overwhelming.

Additional concerns raised by objectors were that 1% of patients receiving the active drug had major side effects, primarily due to the brain swelling that occurs early in treatment, and this was in the setting of a clinical trial, with very close patient monitoring and dose adjustments made based on brain imaging – conditions unlikely to be met in the real world. Finally, patients in these trials were very carefully selected, with mild AD and with specific findings in the brain on PET scans, scans not covered by Medicare or most health insurers.

AD is such a devastating illness, with tragic impact on both the sufferers and on their caregivers, that I fear the pressure on physicians will be overwhelming to prescribe aducanumab to every AD patient for want of any good alternatives. This is likely to harm more patients than it helps. It will also add to the already enormous cost burden faced by patients and their families, as the cost of the drug is unlikely to be paid by many commercial insurers and no insurer will pay for the associated scan costs.

The FDA’s role is to protect the public from pharmaceutical companies’ natural desire to market products on which they have spent huge amounts of development and testing money. In the case of Biogen, the FDA has failed the public.

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