The Expert Committee on Water Fluoridation of the World Health Organization (1958) stated that "Hundreds of controlled fluoridation programmes are now in operation in many countries. Some have been in progress for the past 12 years, so that conclusions are based on experience." This statement suggests that there is a large amount of experimental evidence in regard to the process of artificial fluoridation. It is very doubtful whether this is the case. If hundreds of fluoridation programmes have been conducted with experimental controls, it is strange, and very unfortunate. that such a large body of data has not been published; for, except in the cases of the trials which have been considered here, published data concerning fluoridation trials are very meagre. It would seem, therefore, that the Expert Committee did not use the term "controlled" in its experimental sense, but in that of regulated measurement of the fluoride salt, such as in its statement that "The precision of fluoride application should be carefully controlled."
The United Kingdom Mission (1953) which visited North America in 1952, in its report referred to "the Fluoridation Studies", and enumerated only six study centres; and Jenkins (1955) mentioned "the six study centres on the American continent". In addition to the four test cities which have been considered, the Mission referred to Sheboygan, Wisconsin, and to Marshall, Texas. No control city for Sheboygan was mentioned; and the Mission stated that in the latter study "The neighbouring town of Jacksonville with a fluoride-free water supply was selected as control, but although caries experience in the two areas was compared after 2 1/2 years of fluoridation, the most valuable basis for comparison is the baseline data of Marshall itself." The Mission quoted two unpublished reports as the source of its information in regard to the latter study. An indication of the minor importance of these two trials is the fact that in the 240-page report of the New Zealand Commission of Inquiry (1957) no data from them were presented, the former city being mentioned twice and the latter only once. Furthermore, the directors of these studies, Doctors F A. Bull and E. Taylor, were not named in the report, and the extensive bibliography did not include any papers published by them.
The crucial importance, even at the present time, of the trials conducted in Newburgh, Grand Rapids, Brantford and Evanston was demonstraled by the report made in 1957 by the New Zealand Commission, the hearings of which did not conclude until April of that year, and by the report of the Expert Committee of the W.H.O. (1958), which met during August 1957. The only evidence mentioned by the Commission with regard to the dental results of the addition of fluorides to water supplies was that obtained in those four cities. The Expert Committee referred to only the first three of those cities in the few lines of its report which mentioned dental results of fluoridation.
In discussing the general design used in fluoridation studies, the United Kingdom Mission (1953) said: "In a fluoridation study, two nearby towns, comparable in all respects, are chosen, both having an almost fluoride-free domestic water supply, preferably from the same source. The water of one town is fluoridated while that of the other remains untreated, this town serving as the control. Before fluoridation is started the teeth of the children in both towns are examined in detail to ascertain if caries experience is similar and to determine its prevalence in the various age groups. Further examinations are carried out at yearly intervals and the dental condition of the children in the fluoridated town is compared with that of similar groups in the control town. The prefluoridation data also serve as a basis for comparison. The caries incidence may also be compared with that in a town where a similar concentration of fluoride occurs in the water naturally. In practice it is often difficult to obtain all these conditions and in some studies there is no independent control."
The term "comparable in all respects" describes a theoretical ideal for a test and a control town rather than a practical possibility. In regard to the other matters mentioned in the design these studies exhibited numerous deficiencies. No control was employed in the City Council study in Brantford, and the Grand Rapids study lost its control in 1951 as a result of the fluoridation of the Muskegon water supply. In the extremely important matter of the water supplies, both the source and the composition of the Newburgh water is considerably different from that of Kingston. Further examinations were "carried out at yearly intervals" only in Grand Rapids-Muskegon, and in Newburgh-Kingston until 1952; if yearly examinations were made in the latter study after that year, the results for all years were not published. In the Evanston trial, only two examinations were made in the control city, and few data from it have been published; in the test city only one age group was examined each year. In Brantford and in Evanston, and in the first and the last dental reports from the Newburgh-Kingston study, data from children of different yearly ages were added, thus introducing the possibility of "weighting". In some instances, at least, the degree of "weighting" found indicated that the comparisons were not being made between similar groups in the test and the control cities. No pre-fluoridation data were gathered in Brantford by the Canadian Department of National Health and Welfare, for that study was not commenced until over two and a half years after the fluoridation of the city water supply.
In all of the studies that have been considered, it has been seen that fluoridation of the water supply of the test city was initiated before the initial caries rates in the control city were known. This late examination of the control cities, on first thought, may not seem to be of much consequence. However, it means that, in all of these studies, a matter of fundamental importance was disregarded-it could not have been established that the children of similar ages in the test and the control cities, prior to the commencement of the experiment, had reasonably comparable caries attack rates. Therefore, the statement of the United Kingdom Mission (1953) that "Before fluoridation is started the teeth of the children in both towns are examined in detail to ascertain if caries experience is similar and to determine its prevalence in the various age groups" appears to have been based on assumptions only.
Caries attack rates may be expressed as decayed, missing and filled teeth per 100 erupted teeth, or expressed as per 100 children or per child. The former method was preferred by the authors of the Newburgh trial "because individual teeth may be subjected independently to the hazard of caries" (Ast et al., 1956). In the Evanston study, the rate per 100 erupted teeth was given, but, curiously, only for children aged twelve to fourteen years. All other cases (the younger children in Evanston, and the other studies) in which the caries attack rates per 100 children or per child were given are based on the assumption, unsupported by published evidence, that in each age group the mean numbers of each category of erupted teeth per 100 children is very similar in the test and the control cities, and that little variation occurs from year to year. If this is not the case, comparisons between the rates prevalent in the test and the control cities, and those seen in different years, are not valid. Feltman (1956) gave fluorides in tablet form td-pregnant women and young children, and reported that "Many children in the study group showed a marked delay in the eruption of the deciduous teeth. This delay is in some instances a cause for alarm by the parents. The second incisor, second molars, and cuspids are the most frequently delayed, in many cases by as much as a year from the accepted average eruption dates." Of course, if fluoridation results in the eruption rate of teeth being retarded, a decrease in caries experience would be expected due to the shorter time of exposure of the teeth to the risk of caries. It will be recalled that data were published in the Evanston study which were compatible with a continuous and marked decline in the rate of eruption of first permanent molars during the first four to five years of fluoridation, but that further comparisons could not be made because this type of data was not published for younger children in later reports.
In order to decrease the chance of misinterpretation, extensive use has been made of direct quotation from the original reports, and to avoid unnecessary repetition, consideration of the comments made on the results reported from these control cities, apart from those made by the authors of these studies, has been restricted to the statements of only a few writers.
It is felt that it is not necessary to discuss further the matters which have been noted above, for they are self-explanatory. It has been shown that the reports of the controls used in these fluoridation trials contain arithmetical and statistical errors, and that results and relevant data were omitted. Also, misleading statements were made which denied, ignored, or underrated the unexplained changes in caries attack rates which took place in the control cities, and which suggested that the pre-fluoridation data from the test cities, and those obtained during the basic examinations in control ones, were more closely comparable than was the case. Jean R. Forrest, the Senior Dental Officer, Ministry of Health, who was a member of the United Kingdom Mission and of the Expert Committee on Water Fluoridation of the World Health Organization, in 1957 contrasted "the emotional type of opposition" to fluoridation, to "the precise correct statements of scientists", However, the situation which has been encountered is more aptly described by the words of Wade Hampton Frost "an outstanding American epidemiologist" (Bews, 1951). More than thirty years ago Frost (1925) said: "It is frequently easy to exhibit some figures which, though not really to the point, will nevertheless serve to impress an uncritical public, and the temptation may be great to give them, at least by implication, an unduly favourable interpretation. It is more difficult and more tedious to present the full argument, based on all the facts, and it is perhaps a little humiliating to admit that the statistical evidence is deficient because we have failed to collect it; but to do this is not only more scientific, it is in the end more convincing, and after all there is no free choice, because it is the only honest method, whether it be convenient or not. Finally, it is the only way of progress, for the first step towards collecting better evidence is to recognize the deficiencies of that which is at hand."
More than eleven years after the initiation of the last of these five trials, the deficiencies of their controls still remain unrecognized. The endorsements of fluoridation by medical and dental associations, by public health authorities, and even the recent one by the Expert Committee on Water Fluoridation of the World Health Organization (1958), appear to have been based mainly on the opinions of the authors and of others. Indeed, in the report of that Committee, under the heading "Results of fluoridation", instead of results being considered, comment was confined to: "Reports of the results after 10 years of controlled fluoridation in three cities". Examinations of the data obtained in these trials, which have been published by other endorsing bodies, are also inadequate or absent. It is an understatement to term this failure regrettable.
In 1951, Appleton stated that in any future fluoridation trial: "The experiment should be genuine, and not one in name only. In designing such an experiment, a careful and competent analysis of those now in progress should first be made, in order to see how they might be improved or extended."
In the early part of this paper some basic experimental considerations were mentioned. In cities in which it is intended to compare the caries attack rates of the children in a fluoridation trial, the three main factors which should be as closely comparable as is practically convenient are the composition of the water supply, the climate and the dental caries attack rates. Four trials having "fluoride-free" control cities have been considered. The composition of Newburgh's water supply is considerably different from that of its control city. There were gross differences between Evanston and its control city regarding the initial caries attack rates in the younger children. In the Department of National Health and Welfare study in Brantford, as the first examination was made over two and a half years after the commencement of fluoridation, it cannot be known what the pre-fluoridation rates in that city would have been, if assessed by those examiners; thus, it cannot be determined how closely the (1945) Brantford rates resembled those of Sarnia. In the Grand Rapids study, the fluoridation of the water supply of Muskegon in 1951 severely limited its usefulness as the control city.
In each trial both the test city and its control were selected. For instance, "Oak Park graciously offered to serve as the control community" for Evanston (Blayney and Tucker, 1948). Two cities which had agreed to participate in the experiment, after having been found suitable for comparison, should have been allotted at random to be test or control. It will be recalled that in at least two of the cities selected as test ones, Evanston and Brantford, "dental care was outstandingly good" (United Kingdom Mission, 1953).
Two statements made by authors of these studies may be recalled. In 1950 Hill et al. said: "It is to be expected that the rate of caries in all teeth varies from year to year due to chance. A significant reduction of caries prevalence can therefore be assumed to exist only when the statistical analysis of the data provides almost absolute certainty that the observed differences are not due to chance." However, as was mentioned in Part One this very important matter of random variation has been ignored in all these studies. Blayney and Tucker (1948) stated that: "A study of this nature must have an adequate control." It has been seen that the controls used in these trials cannot be considered to be adequate.
It would appear that these shortcomings have not been recognized, for those who conducted these studies, and other writers, have expressed their satisfaction with the methods used. For instance, Ast and Chase, the authors of the 1953 report on the Newburgh-Kingston study, referred to "the carefully controlled studies such as the Newburgh-Kingston, Grand Rapids-Muskegon, and the Evanston studies"; and Mather (1957) said: "This study at Brantford was most carefully set up and has been under the strictest control."
Approval of the methods used in these studies was also expressed by the New Zealand Commission of Inquiry (1957), for it considered that: "All these investigations" in Brantford, Newburgh and Grand Rapids "were designed and executed with great thoroughness." The Commission also said: "We have examined the statistical evidence brought forward by the advocates of fluoridation, and the conclusions they have drawn from that material ... We have found nothing to invalidate the statistics or cast doubt on their reliability." It will be realized that many of the deficiencies of these studies can be noted only when different reports from the same study are compared. It seems that the Commission was handicapped in this regard, for although its "List of exhibits produced at public hearings" mentions over 250 items, such as papers, books, charts and letters, it includes only the final report, or the one which was the most recently published at that time, of the numerous reports showing the dental caries attack rates which were published in each of these studies. It would appear that none of the earlier accounts of these trials were shown to the Commission, nor were they mentioned in the "bibliography" of 144 references. None of the reports from the City Health Department trial in Brantford were listed as exhibits. The paper by Brown, Kohli, Macdonald and McLaren (1954a) which is mentioned deals only with gingival results. Although the Commission had the assistance of legal counsel in gathering the evidence, no mention was made of the employment of a statistician to assist its members in evaluating the numerical data.
The Expert Committee on Water Fluoridation of the World Health Organization (1958) also expressed its satisfaction with the methods used in these trials. Out of the hundreds of controlled fluoridation programmes which it stated have been set up, it mentioned only the Newburgh, Grand Rapids and Brantford (City Health Department) studies in the sixteen lines which allotted to the mention, one cannot say consideration, of the results of fluoridation on dental caries prevalence. Presumably these three trials were cited because the Committee considered that they were the most important and reliable studies, and it said that they were "carefully planned and controlled". As this opinion of the Committee was made in referring to the three studies which it cited in mentioning results of fluoridation, it is reasonable to assume, at least in this instance, that the term "controlled" was used in its experimental sense.
If this is the case, the inaccuracy of that statement of the Expert Committee is astonishing, for it will be recalled that, of the three studies which the Committee quoted, the Brantford (City Health Department) study, far from being carefully controlled, was not controlled at all. Furthermore, the control for the Grand Rapids study was abandoned after only six years, at the crucial stage of the trial when the first of the permanent teeth were erupting in the children of the test city who had ingested fluoridated water throughout their lives. Therefore the control , was abandoned before any assessment of caries activity in those teeth could be made. In regard to the remaining study mentioned by the Expert Committee, the Newburgh trial, after the unexplained decreases in the DF rates for deciduous teeth, which were shown as having occurred in Kingston, the control city, between 19456 and 1949, no further caries rates for deciduous teeth were published. Also, the erratic changes which were made in the methods used in this trial are not consistent with careful planning, nor is the choice as the test and control areas of two cities with water supplies which were of considerably different composition.
It has been acknowledged for many years that one of the fundamental procedures in planning an experiment is the establishment of a statistical design for the procedures before work is commenced. The deficiencies in the basic statistical requirements of a good experimental design are only too obvious in all these studies. Therefore, it is surprising that the Expert Committee did not point out these deficiencies, but, on the contrary, described the three studies which it mentioned as carefully planned ones. The importance of these matters is emphasized by the authoritative statement of Fisher (1951) that: "If the design of an experiment is faulty, any method of interpretation which makes it out to be decisive must be faulty too."
This investigation of reports of these fluoridation trials was instituted when a preliminary examination of the methods used revealed disturbing facts, and solely because it was felt that, as Appleton (1951) expressed it: "Professionals and specialists have the duty of insisting upon a scientific demonstration of a high probability that a proposed method will be useful and safe, before it is recommended for general adoption. The maintenance of this attitude is of paramount importance."
The deficiencies of these trials not having been recognized, many cities have already fluoridated their water supplies on advice which is based largely on the results that have been considered. It is, therefore, an important and urgent matter that a more accurate assessment of the efficacy of this process should be obtained, but, unfortunately, it appears that little long-term experimental evidence is available. Therefore, despite the limitations imposed by the methods used in these studies, consideration should be given to a careful and competent examination of the whole of the original data obtained in them. The findings resulting from such an examination would be of assistance in designing future fluoridation trials, and would provide a far more adequate assessment of the results reported from these studies than it is possible to obtain from an examination of the very limited data that have been published.
At least until such a report is available for examination, it would be wise to maintain an open mind in regard to the efficacy of artificial fluoridation.
(a) odd experimental and statistical methods;
(b) failure to consider random variation and examiner variability, and to eliminate examiner bias;
(c) omission of relevant data;
(d) arithmetical errors;
(e) misleading comments.