Canada’s Dr Safety, Ed Napke, has died aged 99. The inventor of the pigeonhole "alert system" for adverse reactions was a fearless and determined campaigner for public health and the safer use of medicines.
BORN IN LEBANON IN 1924, his family moved to Canada when he was very young. There he studied and went on to obtain a BSc at the University of New Brunswick in 1945, then his medical degree from the University of Toronto in 1951, and a public health degree in 1968 from Toronto.
A turn of fate took him down the path of ground-breaking research on adverse effects from medicines not related to active ingredients, triggered by excipient components, and the almost infinite range of potential interactions resulting from a person’s diet, gender, age, genetics, lifestyle, location, and other variables. Unlike others at that time, he advocated not being limited to reporting single event terms, or even a collection of such terms, but recognised the importance of ‘syndromes’, both in the medical sense, and in finding collections and patterns in nature.
His research caused a stir in the research community; Ralph Edwards wrote, in the preface to the 2009 UMC collection of Ed Napke’s writings and thoughts, that he was “one of the pioneers in pharmacovigilance, and much else, whose work over the years has always brought the fresh air of innovation and controversy into medicine”.
Ed had a very broad view of his job which from the start he perceived as patient safety.....He energetically promoted the concept that any medicine is a cocktail of chemicals and not just an active ingredient.
In the early 1960s, a friend asked him to join the Canada Food and Drug Directorate because of the post thalidomide drug regulations. Believing it would only be for two to three years, in 1963 he and one other doctor began to medically review new drug submissions, which resulted in several visits to the US FDA. In 1965, he was asked to create the Canada Adverse Drug Reaction Reporting Program within the drug regulatory body. He decided to expand monitoring from drugs to all products on the Canadian market and had inherited a fast-expanding poisons control programme, and he renamed the ADR Reporting Program the ‘Product Related Disease Division’. The resulting database included all prescription and over-the-counter drug and veterinary products, vaccines, medical devices, cosmetics, foods, herbs, alternative medications, beverages, water pollutants, pesticides, and herbicides. This was a farsighted move, the only other centre considering monitoring other chemicals as well as medicines was being developed in New Zealand by his friend and colleague, Prof Garth McQueen.
Despite his considerable influence on pharmacovigilance research, Ed Napke is most well-known for using bold and adventurous approaches to managing case reports for ADRs. It was he who convinced WHO to accept Canadian ADR data on computer tapes rather than WHO forms, thus becoming the first country to do so. Ed is especially remembered for his ‘pigeon-hole alerting system’, where each ADR report could have up to five colour tags and thus be put in several different pigeon-holes. He said, “I wanted to visualise clusters of case reports, which with each report colour-tagged and time-slotted gave the onlooker an instant message”. The data were also computerised so that he could fine tune and alert and advise his regulatory body.
In 2009, Edwards noted “We certainly should have learned many lessons from Ed, though in my view we have some important ones still to adopt. The principle [of the ‘pigeon-hole system’] is the same as the computerised automatic data mining we use now, but this was done in the 1960s, and was very effective at minimal cost. Ed had a very broad view of his job which from the start he perceived as patient safety. He recognised the benefits to be gained by having a single national organisation monitoring poisons and devices as well as medicines, including herbals. Ed also took a broad view of what constitutes a drug and of adverse reactions. He energetically promoted the concept that any medicine is a cocktail of chemicals and not just an active ingredient.”
Edwards has also often alluded to Ed’s ability to entertain. One of Ed’s acts was to simulate, using only his mouth, the sound of a horn or trumpet: it was very convincing. With sadness he recalls one of Ed’s performances at the end of a day of meetings, was to simulate a horn playing the haunting ‘Last Post’, and that is perhaps a fitting way to both remember and say goodbye to an extraordinary, wonderful person.
To me adverse drug reaction monitoring is a commitment, not a job.
Ed Napke led the Canadian pharmacovigilance programme from its beginnings to 1990; in Uppsala Reports 25 (April 2004) he declared “to me adverse drug reaction monitoring is a commitment, not a job”. He continued work in the 90s and beyond as a keen founding member of the signal review panel in the Uppsala Monitoring Centre, as well as a co-author of an important and still cited paper on what might constitute a true signal from the aggregated data of case reports.
Alongside his work with medicines, he worked to create ‘warning’ statements on household products and over-the-counter medications, as well as getting involved in ‘child-resistant packaging’ legislation. His ongoing contact with Canadian Government departments and those concerned with chemical pollutants in water, air, and soil and their effect on humans, and other fauna led to his involvement with environmental groups and in cigarette smoke control groups.
One such unusual success story was the ‘beer–cobalt’ episode in Quebec in the mid-1960s where a brewery was allowed to add cobalt to beer to prevent foaming. Shortly after, a significant number of young, fit men became seriously ill with heart failure, and some died. He went to investigate and talking with the patients it became apparent that they were protein deficient. They drank huge volumes of beer (and cobalt) but had little food except some clear soup – the cardiac pathology was unique. The brewer dumped all its cobalt-tainted beer into the river – and went out of business – and the epidemic ceased.
Over the years Ed Napke held positions at McGill University, Psychopharmacology Division, at Ottawa General Hospital, at the Institute of Clinical Toxicology, Houston, Texas, the Memorial University of Newfoundland, and with the Royal Ottawa Hospital Chronic Fatigue Syndrome programme. In 1971 he was made an honorary member of the National University of Buenos Aires, in Toxicology, and in 1971 the Latin American Association of Toxicology made him a Correspondent Member.
His legacy lives on in the many people he has inspired through his work and research, such as Dr. Viola Macolić Šarinić, a scientific officer at the European Medicines Agency and member of the WHO Advisory Committee on Safety of Medicinal Products. “[Ed Napke was a] Wonderful and brilliant mind serving public health, and at the same time a modest and kind human being. Ed Napke’s name I came to know as a medical student and is one of those who inspired me to dedicate my professional life to pharmacovigilance. I also had the privilege to meet him in person when I became a pharmacovigilante.”
What better way to end an obituary for such a mind than with words from the brilliant man himself. For the 2018 UMC anniversary book Ed Napke summarised his outlook on disease prevention with the quote that we “must also return to the idea of preventing disease through good nutrition and exercise. Healthy bodies are cheaper, so we simply need to help people live better lives, with less fear. And I think that’s a hopeful message for the future”.
Edward Napke M.D., D.P.H.
21 January 1924 – 13 February 2023
I R Edwards et al, “Quality criteria for early signals of possible adverse drug reactions”, Lancet, 1990.
E Napke, "The Canadian Drug Adverse Reaction Reporting Program", Therapeutic Innovation & Regulatory Science, 1975.
E Napke, D G Stevens, "Excipients and additives: hidden hazards in drug products and in product substitution", CMAJ, 1984.