Wednesday, May 27, 2020

Musings on masks

Let me start with the punch line and then work backwards.

You do not wear a face mask to protect yourself, though it may offer some modest protection. You wear one to protect your fellow human beings. Refusing to wear a mask does not indicate bravery and toughness but rather a lack of concern for others.

How does the coronavirus spread? It spreads almost entirely when viral particles are expelled from the respiratory tract of an infected person and inhaled by another person. Huge numbers of viral particles are spread when an infected person coughs or sneezes, large numbers when they sing or shout, and fewer but enough to spread with normal talking or even breathing.

Who can be a virus spreader? Alas, it is not only people who are obviously ill. There are still gaps in our knowledge, and it is hard to give exact numbers, but all experts agree, backed up by increasing data, that many people who harbor coronavirus and can spread it have minor or no symptoms. The most recent study I found, published in a British medical journal, found that 81% of passengers on a cruise ship who tested positive had no symptoms when they were tested. Moreover, even those who develop symptoms are most infectious just before symptoms develop. Lack of symptoms seems to be more common in women than men, and in younger adults. Roughly half the Covid-19 patients in China appeared to have been infected before the patient from whom they caught it knew they were sick.

How much do masks protect the wearer? Probably not a lot. Only N95 masks, which remain in short supply and are needed by healthcare workers, filter out most viral particles, which are very small and can pass through the fabric of cloth or disposable surgical masks. They do offer modest protection against moist droplets which carry viral particles from a sneeze or cough.

The masks do cut down on spread of the droplets generated by speaking, coughing or sneezing. The key point is not that masks do not block every virus particle, but that they filter out many. Every virus particle that does not escape into the air is a virus that will not be inhaled by others or fall on surfaces and perhaps be picked up on the hands of others.

Just as wearing a seat belt does not confer immortality if you get in a car accident, but does cut down on deaths, wearing a face mask will not prevent all spread of coronavirus but will reduce it. Wearing a mask is an easy, inexpensive and harmless way to show that you care about others.

Prescription for Bankruptcy. Buy the book on Amazon

Friday, May 22, 2020

Surrogate or real?

The dictionary defines surrogate as “a person appointed to act for another,” and to the general public probably the most common use is in terms such as surrogate parent

In medicine, it is common to have surrogate decision-makers, such as the parents of a minor child, or the spouse or child of a person who is incapable of making their own decisions. Such surrogate decision makers have all-too-often been put in the difficult position during the COVID-19 pandemic of making dread decisions such as whether to have a loved one put on a ventilator. It is very common for an elderly patient to undergo intensive care when they have asked this not be done, and researchers have also found that many surrogates’ wishes are not followed by the medical staff. It is always best, and Covid-19 has just underlined this, for a older person (or a person of any age with serious medical problems) to be sure their wishes regarding the trade-off between possibly life-sustaining care and comfort be explicit, in writing, and discussed with family.

I want to focus, however, on another form of surrogate – the use of “surrogate end points” to approve a new drug.

The gold standard for proving that a new treatment works, or works better than an existing one, is the controlled clinical trial. A large group of patients are randomly given Drug X or Drug Y, or, if there is no existing useful treatment, Drug X or a placebo. They are then followed until a pre-specified outcome occurs and the results of the two groups compared. As regular readers of these posts know, I am much more impressed with a trial that uses death as the outcome being measured. For many of the events reported, the definition is often fuzzy. The research group frequently establishes a committee to “adjudicate” whether an event occurs. You do not need a committee to decide if a patient is alive or dead.

From a researcher’s perspective, the problem with using death as the outcome is that to establish that one treatment is better than another may take a large sample followed over a long time unless the disease is rapidly lethal. Large trials over a long time are costly to perform.

Enter the “surrogate.” The trial of a cancer drug may use “shrinking of the tumor by 50% on CT scan” or “reduction of a biomarker (blood test)” as the outcome studied. While these MAY correlate well with outcomes of more value to the patient, such as lifespan or quality of life, they may not. More and more cancer drugs are now being approved by the FDA based on surrogate outcomes. A recent study published in JAMA Internal Medicine found only a very weak correlation between these end points and overall survival. While a drug approved on this basis is supposed to have further tests done that do track overall survival, in a large percentage these studies are never done. Since these new drugs are often very expensive and have many major side-effects, it appears that patients are often exposed to potential harm with minimal potential meaningful benefit.

So, when the latest “wonder drug” is suggested, be sure to ask just HOW wonderful it really is. The reported results may be “statistically significant,” but are they clinically significant? Can anyone tell you this treatment will make you feel better or live longer, or will there just be a meaningless "surrogate" improvement?

Prescription for Bankruptcy. Buy the book on Amazon