A simple question that seems to be unanswered but should be answered, says Richard Smith

I don’t think that I’ve ever had the flu, certainly nothing that affected me for more than a day, but last year I had the influenza vaccine for the first time. Three factors influenced me: two tough friends who had each for the first time spent a week in bed with the flu; the doctor telling my wife that she should have the vaccine “for the sake of others”; and an Australian critical care doctor telling me on Twitter that they had in their winter that precedes ours seen more severe cases of flu than usual. Unfortunately I developed flu-like symptoms within a few hours of my vaccination, leaving me wondering who is most likely to have side effects from the vaccine. Could it be that I was having it for the first time? Will I be likely to get them again if I’m vaccinated next year?

I have deliberately delayed in posting this blog because I don’t want to put people off having the flu vaccine. The flu season is now largely over, and I have not had the flu. Indeed, I haven’t had any illness at all since my flu vaccine. By the autumn when the time will come again for the influenza vaccine my blog will be forgotten and not discourage anybody for being vaccinated–but the research questions I’m posing will still be valid.

I had both the influenza vaccine and the pneumococcal vaccine at the same time through the same needle in the morning. I hadn’t gone to get the pneumococcal vaccine, but the nurse suggested that I have it as well. Immediately afterwards I cycled seven miles to and from a lunch with a friend on a delightful sunny day. We even ate our lunch out of doors, which is unusual for London in December. It wasn’t until the evening when I began to shiver and feel cold. My arm was red, hard, and sore where I’d been vaccinated. I went to bed but slept badly, unable to sleep on the side vaccinated, and becoming feverish during the night. The next morning I felt grotty and looked up the symptoms of adverse effects from influenza vaccination on NHS Choices. The side effects are said to occur in between one in 10 and one in 100 people, so I’d been unlucky. The side effects includes headache, aching muscles or joints, fever, feeling generally unwell, sweating, shivering, fatigue, and pain, swelling, redness, bruising or at the injection site. I had a full house. None of the symptoms were severe, but they were enough to stop me having an effective day. I went to bed early, slept soundly, and the next morning I was fine.

(Illogically I didn’t when this happened look up the side effects of the pneumococcal vaccine, but I have now and they are similar and seem to be commoner. Perhaps in retrospect I reacted to it rather than the flu vaccine; and perhaps reactions are commoner if they are given together. That’s another research question. Despite my illogicality I think that my suggestions for research still apply—and to the pneumococcal vaccine as well as the flu vaccine.)

I wondered if I could find an answer to the simple question of “Who is most likely to experience adverse effects of influenza vaccination?” Might it be related to age, gender, having the vaccine for the first time, having reactions in the past, being pregnant, a history of not having the flu, or other factors?

The first paper I found, from JAMA, seemed to conclude that there are no side effects; I had imagined them or, as my wife correctly pointed out, it might be coincidence that I had the vaccination and then symptoms from some other cause. That was hard for me to believe, but I knew that she could be right. Perhaps she was. The JAMA authors randomised 336 people to either the vaccine or placebo and found the same incidence of side effects in the two groups, suggesting that there were no side effects attributable to the vaccine. But if side effects occur only in, say, one in 20 or even fewer people the study is clearly underpowered (meaning there aren’t enough people in the study to reach a confident conclusion).

Another study looked at the frequency of side effects in 816 people, of whom 650 (80%) responded to a telephone survey. About one in 20 reported fever, and one in 10 “disability.” One in seven of those called after seven days reported a “flu-like illness” (although many of them without fever presumably) within two days of being vaccinated compared with one in 12 phoned after three weeks, suggesting that some of the people called later had not been much incapacitated or they would have remembered their flu-like symptoms. The overall conclusion is that: “These symptoms did not result in a decreased ability to perform usual daily activities.” I would, I think, have struggled with my flu-like illness to go to work if I had to, even though in seven years at school I missed not a day and only two days in 25 years at The BMJ.

So I couldn’t find an answer to my simple question of who was most likely to get side effects from influenza vaccination despite hundreds of millions being vaccinated every year. I was also left with the conclusion that researchers are much more interested in efficacy than side effects, which fits with the observation that adverse effects are poorly collected and poorly reported in randomised trials. Indeed, I found two systematic reviews of multiple trials of effectiveness. It’s understandable that researchers, particularly those who develop vaccines, will be much more interested in efficacy than side effects, particularly in the context of antivaccinationists making a tremendous amount of noise about mostly false adverse effects of vaccines. The researchers, who will rightly believe in the great effectiveness of vaccines, will not want people to be put off from being vaccinated. But patients are interested in both efficacy and side effects, and if they are to give genuinely informed consent they need high quality evidence on both. The nurse who vaccinated gave me no information at all (perhaps because she knew I was a doctor, and I didn’t ask) and told my wife there were no side effects (perhaps she’d read the JAMA trial).

I’d like some young researcher to do a simple case control study to answer my question of who is most likely to have an adverse reaction to influenza vaccination.

Richard Smith was the editor of The BMJ until 2004.