Hugh Tunstall-Pedoe overview of the WHO Surveillance Study MONICA
I first met Zbynek Písa, MONICA’s godfather, in 1969 in the office of Professor Ron Prineas from Minneapolis. Prineas was a consultant at these early meetings. We used the European Myocardial Infarction Community Registers (3), the Minnesota Field Survey Manual (12) and Cardiovascular Survey Methods (11) to plan the study. In 1981 I moved to Scotland and helped to initiate Scottish MONICA, fortunately for me, as England did not participate.
Months later I attended a World Health Organization Working Group Meeting in Copenhagen. Zbynek Písa told me that, as the English-language participant, I was to write up the proceedings—in WHO terminology I was the Rapporteur. I had brought my family with me for a holiday. I never did so again. Diagnostic criteria for definite myocardial infarction were based on a WHO document of 1959 (2). This provided, with illustrations, two electrocardiographic criteria: development of new Q waves, and evolution and disappearance of an injury current in three stages. A footnote said that an injury current was not necessary if new Q waves were observed. I questioned whether evolution of an injury current was also sufficient—otherwise it was illogical and redundant. Nobody knew. I summoned up courage and inserted ‘and/or’ between the two criteria where they have remained ever since (3, 4). Diagnostic criteria are not just descriptions—they have to be watertight and to be able to classify potential cases consistently, something often forgotten even now (5).
Quality control
At the next meeting I suggested circulating test case-histories, to see whether coding was consistent. I was asked to do so. Results showed major disagreements on certain items, and failure by some participants to understand why these were included. One group claimed that all their coronary deaths occurred in hospital. It was a minority in the other centres. The explanation given by the group was that nobody was dead until a doctor said so: there were no doctors outside the hospital. Jerry Morris chaired this meeting. He insisted that we start again using only data collected after key items had been more specifically defined. However, earlier data re-emerged in the final publication. Looking back now it was rather primitive—bundles of incomplete record forms being sent to and fro across Europe. Although we had defined definite and possible myocardial infarction, the latter including some very borderline cases, results were pooled in the final analyses. Zbynek Písa, by this time in Geneva, asked me to write a chapter on methods for a monograph on Myocardial Infarction Community Registers (3). I did so, stating what had worked, what had not, and identifying problems. The chapter was acknowledged, but the monograph appeared without it. I was told later that my chapter was “not quite what was wanted.” By this time I was working on another WHO study with coronary end-points, the European factory study, with Professor Geoffrey Rose (6). I published my critique of heart attack registers in a cardiology journal, its title honouring Jerry Morris (7).
Preparations for MONICA
In 1979 Zbynek Písa asked me to send him reprints of this critique to be used as a working document for a small meeting that followed the Bethesda Conference on the Decline of Coronary Heart Disease Mortality (8). The plan was to revive heart attack registration so as to study trends over time. That year I spent several weeks in Minneapolis at the then Laboratory of Physiological Hygiene, Stadium Gate 27, where the Minnesota Heart Survey was being launched to monitor trends in coronary disease and risk factors. This was the home of the Seven Countries Study (9), and of Minnesota coding of the electrocardiogram (10), as well as the joint parent of Cardiovascular Survey Methods (11). Immediately after Zbynek Písa’s small meeting in September 1979 he asked me to be Rapporteur at another meeting taking place two months later in Geneva, and to draft the outline of a protocol for a study of trends by listing the subject headings in preparation for this. So began my involvement with a series of meetings leading to MONICA. Ron Prineas from Minneapolis was a consultant at these early meetings. We used the European Myocardial Infarction Community Registers (3), the Minnesota Field Survey Manual (12) and Cardiovascular Survey Methods (11) to plan the study. In 1981 I moved to Scotland and helped to initiate Scottish MONICA, fortunately for me, as England did not participate.
Development of the protocol and the name
Attendance at early meetings changed but the Chair, Fred Epstein , and the Rapporteur, I myself, did not change. There was creative tension between his ambitious wish to relate trends in cardiovascular disease to ‘changes in known risk factors, daily living habits, health care and major socioeconomic features measured at the same time in defined communities . . .’ (13) and my wish to define what was feasible and measurable. The group discussed the title of the project. I suggested ‘determinants’ for risk factors and argued for ‘multinational’ rather than ‘international.’ Zbynek Písa had doubts about ‘multinational’ but the long title was being spelled out as Multinational Monitoring of Trends and Determinants in Cardiovascular Disease, when Tom Strasser, a medical officer in the CVD Unit (subsequently with the World Hypertension League in Geneva) cried, “In that case you will have to call it the MONICA Project!” The short name and the long name remained.
‘MONICA’ was a marvelous name. It was one of the first studies to be given an acronym. Others copied it. Many knew about MONICA years before we produced any results, because the name intrigued them. In 1998 during the summer ‘silly season’ when there was little news, press reports of the initial results of MONICA that we had presented at the European Congress of Cardiology in Vienna, mischievously suggested that there was no connection at all between coronary risk factors and coronary risk. The name MONICA was so topical for other reasons to do with the American presidency that I was able to use it to obtain very rapid publication of an article refuting the media misrepresentation (14).
Fred Epstein was a charming and accomplished chairman. He knew that meetings could not draft documents. When we reached a controversial subject, and four different speakers had produced five opinions on what we should do, he would say: “Thank you everybody. We will now move on to the next topic. We can safely leave what you have said with our excellent Rapporteur.” I would then struggle to produce a proposal that was sensible and feasible. By the next meeting former protagonists had forgotten their previous positions, and would suggest minor changes in wording. It took months of work, with visits to Geneva between meetings. I was once there to consult on psychosocial studies and measuring medical care. The WHO expert on the latter told me that we could not record quality of coronary care, because medical intervention in chronic disease generally made outcomes worse—an orthodox view around 1980, just as the extraordinary coronary care and secondary prevention revolutions were beginning. Luckily, we ignored his advice.
Ten years had made a big difference to the science of such studies. Monitoring of trends meant trying to detect small changes. Quality control was essential. Training and testing were fundamental. I was again struggling with diagnostic criteria which, this time, were more quantitative (4), and with preparing and marking endless series of test case-histories. Early meetings of Principal Investigators were preoccupied with quality assurance, with announcing results of quality control exercises, and with coding workshops. I remember a cry from the floor once, “Quality control, quality control, I have never heard of such a study for quality control!” It was not mutiny as the centre concerned followed decisions carefully, once they were made.
Early years
We spent a long time waiting for results to accrue in the Data Centre in Helsinki and to pass our numerous checks. The first collaborative population survey results on risk factors were published in 1988 and 1989 (15, 16). Although there was concern about aspects of quality control and response rates, population surveys were a well-established epidemiological routine. Results from coronary event registration, however, took considerably longer. In 1990, as head of the Quality Control Centre for Event Registration I reviewed data then available in the MONICA Data Centre in Helsinki, and reported back to MONICA Collaborating Centres in a MONICA Memorandum (17). It was ‘crunch time’ for MONICA. Data from only a handful of MONICA centres were publishable, the majority having overlooked an important protocol requirement. They had submitted only cases satisfying MONICA diagnostic criteria, not those clinically diagnosed as myocardial infarction or coronary deaths that failed the criteria. (A similar problem existed with stroke.) This meant that numbers of MONICA coronary events, if fatal, were smaller than numbers of coronary deaths in local statistics. A similar situation applied to non-fatal myocardial infarction. We needed fully coded details of all false-positives to be made available, to prove that reported cases were not being overlooked (13, 18). Round the world, MONICA Investigators had to go back several years and send in record forms for the missing false-positive cases. Everybody did so with good grace. The first cross-sectional paper on coronary events was published in Circulation in 1994. It was a paper with a worldwide impact and has been cited since more than 500 times (4).
Maturity
Following the publication of cross-sectional results came years of data accumulation, discussion of data quality, and of centres failing to meet deadlines for essential data. Some discussions were interminable and slow to resolve. After one MONICA Steering Committee meeting I suggested to the then Chair that I re-circulate the minutes from the previous year to see if anyone noticed the difference. He was not amused. Eventually we parted company or lost contact with failing centres. We were then able to concentrate on the long-term data we had, and how it should be analysed.
Finding that the Lancet was interested in publishing our 10-year results by fast-tracking made an enormous difference. Some MONICA papers had spent months or years with particular journals, or had received referees’ comments that disheartened the original authors, who moved on to other things. Knowing that editors were interested and waiting was a great stimulus, although the papers concerned still needed an enormous effort both in submission and in dealing rapidly with referees’ comments (19–21). Although the main results papers of MONICA were well received, a problem has always been that tables with 30 rows or more for different populations, and numerous columns, are difficult to read. Editors prefer tables to figures. Figures usually appear in black and white, too small for individual results to be read with ease. Most readers of the papers would not study the tables carefully and this would be true even of many statisticians and epidemiologists. While preparing the main results papers for MONICA, however, we showed superb colour slides at scientific meetings. But these were too transient for the audience to identify specific populations, and were not published.
This monograph provides the opportunity to celebrate the MONICA Project at 23 years, to make our results and data available in one place to scientists, students and teachers, and to publish our coloured graphics for general study. Publication marks the end of a classic era. MONICA was launched when individuals and funding bodies were sympathetic to a 10-year commitment to answer a major problem. We are now in an era of rapid results, ‘more bangs to the buck,’ and multiple career moves. MONICA finally took over 20 years, a third of my life and proportionately more of the lives of those who are younger. MONICA investigators refer to the MONICA family with the men questioning whether MONICA was a wife or a mistress. Either way it is improbable that we will see her again—despite many of us suspecting that 20 years of data on trends would have helped to answer many of the questions that were left unresolved by 10. (Hugh Tunstall-Pedoe)
References
1. Morris JN. Uses of Epidemiology, London, Livingstone, 1957.
2. Hypertension and coronary heart disease: classification and criteria for epidemiological studies. Geneva,World Health Organization, 1959 (WHO Technical Report Series, No. 168).
3. World Health Organization Regional Office for Europe. Myocardial infarction community registers, Copenhagen, 1976 (Public Health in Europe 5).
4.Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, Arveiler D, Rajakangas AM, Pajak A, for the WHO MONICA Project. Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation, 1994, 90:583–612. PMID: 8026046. MONICA Publication 16.
5. The Joint European Society of Cardiology/American College of Cardiology Committee. Myocardial infarction redefined—a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. European Heart Journal, 2000:1502–1513.
6. World Health Organization European Collaborative Group. Multifactorial trial in the prevention of coronary heart disease. 1. Recruitment and initial findings. European Heart Journal, 1980, 1:73–80. PMID: 7026247.
7. Tunstall-Pedoe H. Uses of coronary heart attack registers. British Heart Journal, 1978, 40:510–515. PMID: 656216.
8. Havlik RJ, Feinleib M, eds. Proceedings of the Conference on the Decline in Coronary Heart Disease Mortality, October 24–25, 1978. Washington, DC: National Heart, Lung and Blood Institute, 1979, NIH publication No.79-1610, DHES.
9. Keys A. Seven Countries: A Multivariate Analysis of Death and Coronary Heart Disease, Cambridge, Mass. And London, England, Harvard University Press, 1980.
10. Prineas RJ, Crow RS, Blackburn H. The Minnesota Code Manual of Electrocardiographic Findings: Standards and Procedures for Measurement and Classification, Littleton, Mass. And Bristol, England, John Wright, 1982, ISBN 0-7236-7053-6.
11. Rose GA, Blackburn H, Gillum RF, Prineas RJ. Cardiovascular Survey Methods. 2nd ed. Geneva, World Health Organization, 1982 (Monograph series No. 56).
12. Laboratory of Physiological Hygiene. Survey Manual of Operations 1981–82, Minneapolis, Minn., University of Minnesota, 1981.
13. WHO MONICA Project. MONICA Manual. (1998–1999). Available from URL: http://www.ktl.fi/publications/monica/manual/index.htm, URN:NBN:fi-fe19981146. MONICA Web Publication 1.
14. Tunstall-Pedoe H. Did MONICA really say that? British Medical Journal, 1998, 317:1023–1023. PMID: 9765191.
15. Pajak A, Kuulasmaa K, Tuomilehto J, Ruokokoski E, for the WHO MONICA Project. Geographical variation in the major risk factors of coronary heart disease in men and women aged 35–64 years. World Health Statistics Quarterly, 1988, 41:115–140. PMID: 3232405. MONICA publication 3.
16. The WHO MONICA Project. A worldwide monitoring system for cardiovascular diseases: Cardiovascular mortality and risk factors in selected communities. World Health Statistics Annual, 1989, 27–149. ISBN 92 4 067890 5. ISSN 0250–3794. MONICA Publication 11.
17. MONICA MEMO 177 of 15.02.90. Eligibility of MCCs for publication of Coronary Event Data. Internal MONICA Document distributed to all Principal Investigators.
18. Mähönen M, Tolonen H, Kuulasmaa K, Tunstall-Pedoe H, Amouyel P, for the WHO MONICA Project. Quality assessment of coronary event registration data in the WHO MONICA Project. (January 1999).Available from URL: http://www.ktl.fi/publications/monica/coreqa/coreqa.htm, URN:NBN:fi-fe19991072. MONICA Web Publication 2.
19. Tunstall-Pedoe H, Kuulasmaa K, Mähönen M, Tolonen H, Ruokokoski E, Amouyel P, for the WHO MONICA Project. Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA Project populations. Lancet, 1999, 353:1547–1557. PMID: 10334252. MONICA Publication 36.
20. Kuulasmaa K, Tunstall-Pedoe H, Dobson A, Fortmann S, Sans S, Tolonen H, Evans A, Ferrario M, Tuomilehto J, for the WHO MONICA Project. Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations. Lancet, 2000, 355:675–687. PMID: 10703799. MONICA Publication 38.
21. Tunstall-Pedoe H, Vanuzzo D, Hobbs M, Mähönen M, Cepaitis Z, Kuulasmaa K, Keil U, for the WHO MONICA Project. Estimation of contribution of changes in coronary care to improving survival, event rates, and coronary heart disease mortality across the WHO MONICA Project populations. Lancet, 2000, 355:688–700. PMID: 10703800. MONICA Publication 39.
By permission from: Tunstall-Pedoe, H. 2003. MONICA monograph and multimedia sourcebook: The world’s largest study of heart disease, stroke, risk factors and population trends (1979–2002). Geneva: World Health Organization.