The new shingles vaccine: hype or good value for your money?

DRUG BUST
by Alan Cassels

A ‘game changing’ new vaccine arrived on the Canadian market last month, promising to relieve you of the pain associated with shingles. Shingles is caused by the varicella-zoster virus, which can appear as a blistering, painful rash that occasionally leads to complications. There is already a shingles vaccine on the market, but this new one, named Shingrix, is being promoted as “90% effective.” If it’s that good, why would anyone hesitate in getting it?

Since I have studied the marketing messages, I wondered whether Shingrix conforms to my theory that “the bigger the hype, the smaller the likely impact.”

If you were unaware of shingles up to now, that will soon likely change due to what seems to be a heavy, corporate-sponsored PR campaign designed to do what pharma campaigns do best: drive you to your doctor. In this case, by making the disease look incredibly painful and ubiquitous – one in three Canadians will get shingles we are told – our doctors’ offices will soon be flooded with people asking for this new vaccine.

Numerous talk shows on TV and radio, as well as newspaper and magazine articles, have warned of the dangers of the disease. The message here is simple and direct: if you want to avoid the dreaded shingles, you better get the shot. This is like other disease-mongering I’ve seen in the past where conditions like herpes, low testosterone or toenail fungus, among many other conditions, are running rampant and threatening the health and safety of populations. Fear sells and as any marketer knows, “You don’t sell the steak, you sell the sizzle.”

The corporate drug world is hoping this one pays off. FiercePharma (fiercepharma.com), a drug information news site, says that GSK, the manufacturer of Shingrix, “has big expectations for its new vaccine,” also noting, “Analysts have predicted more than $1 billion in 2022 sales for the shot.” Health departments around the country are understandably hesitant to pay for the vaccine because it’s expensive and would add millions to our annual provincial drug bill. There is no firm price yet set in Canada, but in the US, the cost is $280USD for the two-shot regime.

I can understand this hesitancy for three reasons. Given the nature of the research on the vaccine, surprisingly, few of us will ever get shingles (more on that in a bit). Secondly, given the research on the vaccine, based on a three-year trial in 14,000 people, the vaccine doesn’t seem very effective. The final, and perhaps the most worrisome thing, is the research which underpins the vaccine has a high risk of bias, which is to say, there is a high degree of doubt the results seen in the trial are even possible in the real world.

While governments everywhere will be asked to pay for this vaccine and seniors’ groups are already lobbying for coverage, I think we probably have better things to do with our health dollars.

For starters, the major clinical study paid for by manufacturer GSK shows a lot of promise, with newspaper headlines around the world promoting the vaccine as having an efficacy rate of “more than 90%.” That figure is essentially meaningless without important context. In the study of over 14,000 people over 50 who were followed for three years, half were given the vaccine and half the placebo. Of the 7,698 people who got the vaccine, nine developed shingles (a rate of about 0.1%). Of the 7,713 who got the placebo, 235 people got shingles (about 3%). This difference, of 2.9%, translates into what is called a NNV: numbers needed to vaccinate. In this case, it’s about 35, meaning that for every 35 people over 50 who get the two-shot dose of Shingrix, one case of the shingles will be prevented. Another way to say this is 34 out of 35 people will see no benefit whatsoever from the vaccine over three years.

One of the real concerns about shingles is whether it leads to complications such as neuralgia (nerve pain in your face or head). This only happens in about 10-15% of shingles cases and, in terms of the trial, it essentially showed doctors would have to vaccinate 261 people to prevent one case of neuralgia.

People bamboozled into thinking the vaccine is “90%” effective, as opposed to 2.9% effective, might be why we see seniors’ groups begging the government to pay for it. At a cost that could be as high as $300 for the two shots of Shingrix, this means millions of dollars if you were to vaccinate everyone over 50.

While shingles can be nasty and debilitating for some, if we take this study into account, most people don’t develop shingles. In this study, only about 1% of the placebo population develop shingles each year and while that rate may increase with age, can we say this is really a major public health problem deserving of millions of dollars of public money being spent?

There is one other nagging problem with the research on Shingrix: it hurts. In fact, the company’s own reports detailed the commonly reported side effects of the vaccination, which include “pain, redness and swelling at the injection site, muscle pain, tiredness, headache, shivering, fever and upset stomach.” Over 80% of the patients given the shot had some level of pain, as opposed to about 10% of the placebo patients.

My reading of this is the vaccine does not dish out an ordinary “ouchie” typical of when someone puts a needle in your arm. Commentators have explained Shingrix is an ultra painful shot because it’s an ultra potent vaccine. Compared to the placebo, the severity of the side effects of the vaccine were much more intense. The study showed 17% of the patients injected with the vaccine, versus 3% on placebo, had “grade 3” symptoms, defined as symptoms that “prevented normal everyday activities.” This gives a rate of 14% who were harmed to this level. The NNH (number needed to harm) is seven. So for every seven persons injected with the vaccine, one person will have “grade 3” symptoms and have difficulty functioning in everyday activities.

I don’t think the fear of a painful needle should prevent you from getting any vaccine, but there is a problem with this high rate of injection injuries: it unblinds the study.

In other words, if a randomized controlled study is to be believed, patients and clinicians involved must be blind to which treatment individual patients receive. If you know that patients in group A suffer a much higher rate of a certain type of effect over patients in group B, it is much easier to discern whether they were getting the intervention or the placebo. In this case, if the treating doctor knows his patient is getting the vaccine versus the placebo, there may be subtle ways in which his assessment of the patient’s health changes. Basically, it injects a level of subjectivity into the results and we all know “unblinded” trials must always be treated with caution.

There is another type of bias at play here and it’s called “funding” bias. Also known as “sponsorship bias,” the fact is the manufacturer and the researchers had a financial incentive to see a certain result, unlike the independent researchers who were only interested in the ‘truth’ of the vaccine. Again, this means we have to be cautious in interpreting the results.

This is not to besmirch the reputation of the manufacturer or the investigators who studied the vaccine. But, as we do with any drug, we have to ask ourselves, “Is the research believable and if it is, is it likely to be of an overall benefit?”

This is what our doctors and you, the prospective patients, need to ask. Do you want to spend $300 on a vaccine for a one in 35 chance of benefit and a one in seven chance of being harmed? We all need to be involved in ensuring governments and individuals spend their health dollars wisely. And that is why when a new drug or a new vaccine comes around, promising to be ‘game changing,’ everyone would benefit from a sober second opinion.

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Alan Cassels is a former drug policy researcher, a writer and the author of several books on the pharmaceutical industry.