Health Committee Report

SUPPLEMENTARY SUBMISSION FROM ASH

Early reports from Ireland are encouraging.

31st May 2004 - the Office of Tobacco Control in Ireland published its first report on compliance for one month after the smoke-free law came in (covering the period 29th March when the ban was introduced to 30th April 2004). The report comprises of data from three sources: the National Tobacco Control Inspection programme, the smoke-free workplace compliance line and market research on public attitudes and behaviours.

The report found that 97% of premises inspected under the smoke-free workplace legislation were compliant with the law (i.e. no one smoking and no evidence of smoking in contravention of the law) and indicated that levels of visits to pubs and restaurants remained constant, with one in five smokers choosing not to smoke at all when out socialising.

Prior to the introduction of the smoke free workplace law, 91% of the population stated they would be either more likely or just as likely to visit a restaurant to eat. Since the law was introduced, this figure is 92%.

The rate of smokers visiting pubs has remained steady at 74% since the legislation was introduced. The frequency of non-smokers visiting pubs has increased from 67% to 70%.

The full six page report is available on their website www.otc.ie under Publications.

Progress on smoke-free public places is being made elsewhere in Europe.

Tuesday 1 June 2004 - legislation in Norway to introduce smoke free public places is implemented.

May 12, 2004 - the Swedish parliament votes to ban smoking in bars and restaurants, starting on June 1, 2005.

Smoke free New York - one year review shows success.

The Smoke-Free Air Act took effect on March 30th 2003. On May 12, 2004 the New York City Department of Health and Mental Hygiene (DOHMH) announced an 11% decline in the number of smokers in New York City over the previous year - the fastest drop in smoking rates ever recorded nationally. This drop represented 100,000 fewer New Yorkers smoking in 2003 compared with 2002. Those who continued to smoke were also smoking less. The DOHMH attributed the fall in smoking rates to its program of tobacco control, including the ban on smoking in public places.

Concerns had been expressed about the potential economic impacts on business of a ban. Data from the DOHMH one year review showed that:

• Business tax receipts in restaurants and bars were up 8.7%
• Employment in restaurants and bars had increased by 10, 600 jobs (about 2,800 seasonally - adjusted jobs) since the law's enactment
• 97% or restaurants and bars were smoke-free
• New Yorkers overwhelmingly supported the law
• Air quality in bars and restaurants had improved dramatically
• Levels of cotinine, a by product of the body's metabolising tobacco smoke, decreased by 85% in non-smoking workers in bars and restaurants
• 150,000 fewer New Yorkers were exposed to second-hand smoke at work

SUPPLEMENTARY SUBMISSION FROM TOBACCO MANUFACTURERS’ ASSOCIATION (Part 1)

Introduction

On 8 th June 2004, the Tobacco Manufacturers’ Association (TMA) gave oral evidence to the Health Committee on the Prohibition of Smoking in Regulated Areas (Scotland) Bill. During the course of those proceedings the TMA undertook to provide the Committee with certain further information, hence this supplementary written evidence.

The whole debate about smoking in work and public places revolves around and is founded on the assertion that ETS is harmful to the health of the non-smoker. In particular, the Committee asked for further information: on the epidemiological studies which have been undertaken concerning ETS; about the balance of the findings of those studies; and effectively why the TMA did not believe that they justified or supported the popular perception that ETS causes serious diseases in non-smokers. Additionally, the TMA offered to provide further information on legal cases brought against employers.

In order to provide a comprehensive answer to those questions, and to enable the Committee to reach its own conclusions on the available evidence on an informed basis, it is not sufficient simply to list the ETS studies that have been published. The studies need to be put into a proper context, their design and terminology explained and a guide provided as to how their findings should be interpreted.

A chronology

In the US Surgeon General’s reports of 1972 and 1975, initial speculations were raised about the possible consequences of exposure to environmental tobacco smoke (ETS). The US Surgeon General’s 1979 report noted several adverse outcomes that appeared to have an association with ETS; but also that there was only a limited amount of systematic information available regarding the health effects of ETS. The Surgeon General’s 1982 report raised the concern that ETS might cause lung cancer. Following that report a number of epidemiological investigations were published which claimed to show a relationship between ETS and lung cancer.

Then in 1986, the US Surgeon General’s report, as well as reviews by the National Research Council and National Academy of Science (sponsored by the US Environmental Protection Agency (EPA)), concluded that ETS caused lung cancer and claimed an increase in risk of 30%, with the latter two reviews also associating ETS exposure with adverse respiratory outcomes in young children.

However, a review published in 1986 by the International Agency for Research on Cancer (IARC) of the World Health Organisation came to different conclusions. It did not produce estimates of risk but concluded that available studies:

“had to contend with substantial difficulties in determination of passive exposure to tobacco smoke and to other possible risk factors. The resulting errors could arguably have artefactually depressed or raised estimates of risk, and, as a consequence, each is compatible either with an increase or with an absence of risk.”¹

Nonetheless, in June 1989, the US EPA issued a public notice that stated categorically that ETS “is a known cause of lung cancer”. However, the EPA did not provide an analysis of the data on which it had based its conclusion. It was pressed to do so but did not produce its analysis and risk assessment until 1992² . This took the form of a review of selected published studies. It was subjected to devastating criticism, not least by members of the US Congressional Research Service appearing before a Committee of the US Senate, who said:

“The EPA study analysed and summarised 30 studies of passive smoking lung cancer effects. Critics have questioned how a passive smoking effect can be discerned from a group of 30 studies of which 6 found a statistically significant (but small) effect, 24 found no statistically significant effect, and 6 of the 24 found a passive smoking effect opposite to the expected relationship.”

“… our evaluation was that the statistical evidence does not appear to support a conclusion that there are substantial health effects of passive smoking.”³

The report was later also challenged in the courts⁴ where the EPA was found to have knowingly, wilfully and aggressively disseminated false information with far reaching regulatory implications in the US and worldwide. Judge Osteen found that the EPA had :

“changed its methodology to find a statistically significant association . . .In conducting the ETS Risk Assessment, EPA disregarded information and made findings on selective information; did not disseminate significant epidemiologic information; deviated from its Risk Assessment Guidelines; failed to disclose important findings and reasoning; and left significant questions without answers … Gathering all relevant information, researching, and disseminating findings were subordinate to EPA’s demonstrating ETS a Group A carcinogen.”

Yet to this day, despite that judgement which vacated (annulled) the report after ‘forensic’ investigation of the EPA’s review and process, the report is used as a ‘gold standard’ by the authorities. It is the ultimate foundation of the estimates made by UK authorities of UK deaths resulting from exposure to ETS. The report and its methods have subsequently been used as a model for other reports by the Californian EPA⁵ , the National Health & Medical Research Council of Australia⁶ , and the UK’s Scientific Committee on Tobacco and Health (SCOTH)⁷ . In 1998, the US National Toxicology Program accepted the EPA 1992 report and its twin from California as the basis for listing ETS as a known human carcinogen.

At the time the EPA prepared its 1992 report, there were only around 30 published studies seeking to determine lung cancer risks associated with exposure to ETS. There have now been well over 100 studies and reviews that have been published; a great many more are thought to have been undertaken but not been published.

The significance of publication and publication bias

Whilst, therefore, the total number of studies and reviews that have been undertaken is likely to be very much larger, only those that have been published form part of the accepted compendium of information on ETS. This means that every party has access to the same information upon which they may make their own judgements. Unpublished studies are not concealed or used; publication is the determining factor. Such differences of opinion as do exist about ETS studies and reviews arise out of the critical examination and analysis to which they may then be subjected, and the interpretations and judgements which may then be made as to their data and findings.

Given this significance of publication, it is well recognised that what epidemiologists term ‘publication bias’ may arise:

“Publication bias occurs in two quite separate forms. Studies with positive results are more likely to be submitted for publication and more likely to be accepted; and significant findings, such as an association with a particular occupation or exposure, are often given prominence by the authors, particularly in case-control studies [explained at paragraph 21 et seq.], while other exposures that were analysed but were not significant may not be mentioned at all. Both types of bias tend systematically to exaggerate associations in the published literature.”⁸

“Quite different conclusions might be drawn from a review of all published and unpublished studies.”⁹

“The presence of even a modest degree of publication bias can lead to a substantial increase in the estimated risk.”¹⁰

“The result is a biased understanding of the differences and similarities in the disease patterns of populations and an exaggerated view of the importance of associations between risk factors and disease outcomes.”¹¹

Publication bias is well recognised as existing particularly when a consensus develops among the ‘experts’ themselves – albeit that consensus opinion may not be correct . Once a large number of people believe something, it can be difficult and costly to argue to the contrary. For example, academics and researchers who then go against the grain can find it difficult to achieve publication of their opinions and research, or struggle to find posts or research funds.

An illustration of the reception that can be given to the publication of views which do not conform to the accepted wisdom – and which thereby illustrate the strong force that publication bias represents was provided by the reaction to the publication by the British Medical Journal in May 2003 of a major new ETS study¹² , in respect of which the BMJ carried the front-page headline, “Passive smoking may not kill”. This prospective study measured the relationship between ETS, as estimated by smoking in spouses, and long-term mortality from tobacco related disease and was conducted on over 100,000 Californian adults between 1960 and 1998. The conclusions of the study stated:

“The results do not support a causal relation between environmental tobacco smoke and tobacco related mortality although they do not rule out a small effect. The association between exposure to environmental tobacco smoke and coronary heart disease and lung cancer may be considerably weaker than generally believed.”

The publication of the study by the BMJ gave rise to a violent storm of criticism from the medical community. In responding, the editor of the BMJ was minded to comment -

“Of course the study we published has flaws – all papers do – but it also has considerable strengths: long follow-up, large sample size, and more complete follow up than many such studies. It’s too easy to dismiss studies like this as fatally flawed with the implication that the study means nothing . . . I found it disturbing that so many people and organisations referred to flaws in the study without specifying what they were. Indeed, this debate was much more remarkable for its passion than its precision.”

“We must be interested in whether passive smoking kills, and the question has not been definitively answered. It’s a hard question, and our methods are inadequate.”¹³

The heterogeneity of studies and reviews

Whilst it is now common for the statistical findings of ETS epidemiological studies to be expressed in a common manner – in terms of a reported estimated relative risk [explained at paragraph 32 et seq] there is no accepted common study design and “few epidemiological studies satisfy the stringent methodological criteria that should ideally be applied.”¹⁴ . Thus individual studies and reviews exhibit wide variations in design, methodology, data collection, country, population and study size. It is therefore not surprising that findings show little consistency. This makes interpretations and comparisons both difficult and contentious. This is particularly so as even where a positive association between ETS and a disease has been reported, it has been of a very low order of risk, It has been of a magnitude that might easily be accounted for by bias or confounding [explained at paragraphs 24 and 28 respectively], or by inadequate adjustment in the study of such bias and confounding. It has also been of a magnitude well below that normally regarded as being significant and appropriate as a guide for public policy.

Meta-analysis

Given the great variability of individual studies, in undertaking collective reviews of studies, a weight of evidence approach is frequently used. This involves considering the quality of individual studies, discarding some and including others in making an overall judgement. Inevitably, this approach involves a great many subjective judgements about the available studies.

Meta-analysis involves the quantitative synthesis of the results of separate studies, to provide a summary of the pooled results. However, for this to be a valid approach, the studies need to be similar and comparable in design and many other respects, otherwise the result is no better than mixing apples with oranges. Such inappropriate mixes may result from pooling studies of widely varying design and methodology; studies from different countries and populations in respect of which there may be significant and varying confounding variables; studies undertaken in significantly different time frames; and from the selective inclusion of studies based on the researcher’s impressions of study quality.

For example, almost all of the ETS studies that have been undertaken have been of populations outside the UK, particularly in the United States and Asia. They are very different populations to the UK in a great many respects. They have been undertaken over a time period since 1981 and there is a marked difference in the findings between those studies conducted before and after 1989. The difficulties of extrapolating data on one population and applying it to another on the basis that one group of people is broadly equivalent to another has been vividly illustrated by the extrapolation of risk scoring methods for coronary heart disease derived from the US Framingham heart study¹⁵ and its application to the UK. The Framingham study played a key role in quantifying risks such as smoking and high cholesterol. The UK researchers compared the Framingham results with the British regional heart study¹⁶ . They found that using Framingham, there was an over-estimation of the risk of non-fatal coronary events of 57%, and also that 84% of British heart deaths occurred in the 93% of men classified as low risk by Framingham criteria. The fact is that substantial variations in coronary heart disease are found between different regions and different ethnic groups, socio-economic status and family history of coronary heart disease.

Nonetheless, in recent years, meta-analysis has been increasingly used to combine evidence from epidemiological ETS studies of quite different design. This can result in a combined relative risk estimate that has narrow confidence limits [explained at paragraph 35 et seq]; it may appear to be precise, but can in fact be an inaccurate estimate of the true association, if any.

Understanding and interpreting the results of ETS epidemiological studies

“In experimental animal research and in some situations in clinical medicine, for example testing the efficacy of a new drug, it is possible to carry out clinical ‘experiments’ comparing groups receiving different treatments. However, in epidemiological research requiring large populations for the evaluation of potentially harmful exposures, alternative approaches are needed. For example, to ‘prove’ that ETS causes cancer or heart disease would require the conduct of long term experiments (randomised controlled trials) involving hundreds of thousands of individuals half of whom would be randomly assigned to long term ETS exposure and the other half assigned to non exposure. But because it is not ethical to expose human subjects to a potentially harmful substance (in this case ETS), the only research approaches possible are those based on observational studies of non-smokers. Either disease rates in individuals exposed to ETS at home or at work are compared with rates in individuals not so exposed (cohort study); or past ETS exposures are compared in cases (those with the disease in question e.g. heart disease or lung cancer), and in those without these conditions (controls) (case control study). There is no certainty in either type of study that the two groups being compared are similar with respect to other relevant variables. Thus there is the possibility that any differences observed between the groups could be due to factors other than the ETS exposure. If such factors also affect the risk of disease, they are referred to as confounding variables. The consequence is that part or all of the observed association between ETS and the disease may be spurious.”¹⁷

A ‘cohort’ study follows a population group through a lengthy time period. It tracks the disease incidence in the cohort, and can assess possible lifestyle factors and calculate their relationship to the disease incidence. Cohort studies are larger and lengthier than case control studies, and hence are more costly. However, they are thought to be somewhat more reliable than case control studies, especially when multiple risk factors are involved.

However, the vast majority of the investigations that have been undertaken into ETS have been case-control studies . These have typically compared the incidence of certain diseases in non-smokers living with smoking spouses, as compared with non-smokers living with non-smokers. For chronic diseases, such investigations need to assess exposure over a period of thirty to forty years. This is usually achieved through questionnaires - obviously relying on the personal recollections of people - of the intensity and duration of exposure to ETS over a lifetime. The uncertainty involved in this form of data collection makes such epidemiology a relatively imprecise tool.

Bias

In statistical terminology, ‘bias’ relates to deviations from the facts arising from such factors as flaws in study design, data collection or analysis. ETS studies are particularly susceptible to many forms of bias. Aside from the comparative unreliability of individuals’ memories – known by epidemiologists as recall bias - questionnaires are often administered not to the actual members of the populations being studied, but to surviving family members, so increasing recall unreliability and introducing or aggravating other possible sources of bias.

Smokers tend to marry smokers and non-smokers non-smokers and a proportion of people are known not to tell the full facts about their present or past smoking habits. Together, these facts are recognised to give rise to substantial misclassification bias.

Also there cannot be certainty about the precise cause of death, given both the difficulty of establishing that fact and also that “inaccuracies in the registered cause of death are recognised, especially with multiple causes”¹⁸ . In any event, death certificates do not record what caused the illness stated on the death certificate.

Publication bias is also possible – that is the likelihood that studies are published only if they produce positive results or results which conform to the accepted wisdom.

Confounding

Studies are also subject to confounding – distortion because there may be an association of disease with factors other than ETS, such as diet, alcohol consumption, socio-economic circumstances, the level of exercise, the history of disease in the family, that happens to correlate with being in a household with a smoker. While some ETS studies have attempted to collect information on some confounding factors, there has generally been an inconsistency and inadequacy of approach. Yet confounding is a most important consideration in ETS studies. Diseases in smokers that have been associated with smoking are well recognised to be multi-factorial. For example, cardiovascular disease has been associated with over 300 different factors.

There are methodological and statistical techniques to adjust for likely confounding and biases, but again they are not applied uniformly in each individual study, nor are they anything other than devices that may not reflect the true situation, and are themselves subject to limitations.

In reality, therefore, ETS epidemiological studies are statistical exercises, the measurements of which have limited credibility in terms of accuracy. That is not to say that they are irrelevant but it is to put them into a proper context. Epidemiology is “a crude and inexact science”¹⁹ ; and “…until we know exactly how cancer is caused and how some factors are able to modify the effects of others, the need to observe imaginatively what happens to various different categories of people will remain.”²⁰

In other words, epidemiological findings are not incontrovertible, objective conclusions; the judgements made about epidemiological data which indicates a low level of risk, are inevitably subjective. And in the case of ETS, “the judgement as to whether the links observed are causal or not remains difficult.”²¹

continued...

¹IARC, 1986: p.308

² Respiratory health effects of passive smoking: lung cancer and other disorders, EPA, Washington DC, 1992

³ Oral statement of Dr Jane Gravelle & Dr Dennis Zimmerman of the Congressional Research service, the Library of Congress, Washington DC, May 11 1994

⁴ Flue-cured Tobacco Stablization Corporation et al v United States Environmental Protection Agency and Carol Browner, District Court for the Middle District of North Carolina before District Judge Osteen, Order and Judgement, 17 July 1998

⁵ Californian EPA 1997

⁶ NHMRC 1998

⁷ SCOTH 1998

⁸ Peto, J, Meta-analysis of epidemiological studies of carcinogenesis, Mechanisms of Carcinogenesis in Risk Identification, ed Vainio H et al, IARC, 1992

⁹The Lancet, April 23, 2004 on the research commissioned by the National Institute for Clinical Excellence into the prescribing of anti-depressants drugs to children; and The Independent, April 23 2004

¹⁰ Copas J, Shi J, BMJ 2000;320: 417-418

¹¹ Bhopal, R.S, Professor of Public Health, University of Edinburgh, Concepts of Epidemiology, p 91, OUP 2002

¹² Enstrom J E & Kabat G C, Environmental tobacco Smoke and tobacco related mortality in a prospective study of Californians 1960-1998, BMJ 2003;326: 1057-1061

¹³ Richard Smith, editor BMJ, BMJ 2003;327:505

¹⁴ Peto, J ( Institute of Cancer Research), Meta-analysis of epidemiological studies of carcinogenesis, in Mechanisms of Carcinogenesis in Risk Identification, p572, IARC 1992

¹⁵ Dawber T R et al. An approach to longitudinal studies in a community: The Framingham Study, Ann. NY Acad. Sci. 1996; 107:539-556

¹⁶ Brindle P et al, Predictive accuracy of the Framingham coronary risk score in British men: prospective cohort study, BMJ 2003; 327:1267-1270

¹⁷ Report on the health effects of environmental tobacco smoke in the workplace. Commissioned by the Health and Safety Authority of Ireland and the Office of Tobacco Control from an independent scientific group, January 2004.

¹⁸ Derek Wanless, Securing Good Health for the Whole Population, Final Report, HM Treasury, February 2004, 5.49

¹⁹ Dr Charles Hennekens, Harvard School of Public Health, New York Times, 1995

²⁰ Doll R & Peto R, The causes of cancer: Quantitative estimates of avoidable risks of concern in the US today. Journal of the National Cancer Institute 1981:66, 5-6: 1191-1308

²¹ Report on the health effects of environmental tobacco smoke in the workplace. Commissioned by the Health and Safety Authority of Ireland and the Office of Tobacco Control from an independent scientific group, January 2003.

Health Committee Report

SUPPLEMENTARY SUBMISSION FROM TOBACCO MANUFACTURERS’ ASSOCIATION (Part 2)

Relative Risk

Epidemiological studies generally express their findings in terms of reported estimates of relative risk (RR). This is the ratio of the incidence of the disease being studied in the group exposed to ETS (generally non-smokers living with smoking spouses), to the incidence of disease in the group not exposed to ETS (generally non-smokers living with non-smokers).

The RR reported has no direct bearing on the probability that an individual will acquire the disease in question. RR provides only an index of the strength of any association between exposure and a disease, and is always a relative term to the incidence of disease in the non-exposed group.

In case-control studies, relative risk (RR) is most often now expressed as an Odds Ratio, as in the following example:

1.26 (95% CI 1.06-1.47)

In this example, say the RR of 1.26 is the estimated risk of the disease in non-smokers living with a smoker, relative to the risk in non-smokers living with non-smokers. Were it to be less than 1.0, it would indicate that non-smokers living with smokers were less at risk of the disease than non-smokers living with non-smokers.

Confidence Interval

CI is the ‘Confidence Interval’, which is normally stated at the level of 95%. It does not mean that there is 95% certainty that the stated RR - in the above example, 1.26 – is correct. The 95% actually refers to the frequency with which the statistical test used will generate boundaries capturing the true figure. In other words, it relates to the reliability of the test, not to the parameter.

Interpreting Relative Risk

In interpreting what a RR figure means in terms of the population, it is necessary to know what the ratio or incidence of the disease is in the population not exposed to ETS: in other words what the rate of death or disease is in non-smokers living with non-smokers.

As explained in the 1988 report of the Independent Scientific Committee on Tobacco and Health, in the case of lung cancer in the UK population, the rate of death or disease amongst non-smokers living with non-smokers is generally taken to be 10 per 100,000 person-years of the population¹ .

Thus, in the above example, a RR of 1.26 would then mean that amongst non-smokers with smoking spouses, the incidence of the disease would be 12.6 persons in every 100,000 person-years of the population, as opposed to 10 per 100,000 in the case of non-smokers living with non-smokers.

RR is sometimes expressed as a percentage. Most frequently is this the case when the purpose, either of researchers, publications or reporters, is to make the risk more easily comprehended by the public. The outcome is generally the reverse.

For example, when a RR of 1.26 is expressed as an increased risk of 26%, the entirely wrong impression acquired by the ordinary person is that out of every 100 non-smokers 26 will suffer from the disease. What a relative risk stated of 26% indicates is that the incidence of the disease will be 26% greater amongst non-smokers exposed to ETS by their smoking spouses than it would be had they lived with a non-smoker. Given that the rate of death from lung cancer amongst non-smokers living with non-smokers is 10 per 100,000 person years, the percentage increase in risk is from 0.010% (amongst non-smokers living with non-smokers) to 0.0126% a year (amongst non-smokers living with smoking spouses).

However, such a very small increment in risk – 0.0026% - would not make news that demands loud, clear and unequivocal headlines and sound bites. If that kind of message is not provided by the research itself, or by the professional journals publishing their work and wanting to promote their own publications, the danger is that it can then be generated by reporting that lacks thoroughness and concern for detail and accuracy.

A recent example of the misuse of science was provided by an estimate² that claimed that ETS exposure caused the death of 49 workers in UK pubs and bars each year. This figure was arrived at by using relative risks for lung cancer, heart disease and stroke for home and workplace exposure that were used in a New Zealand review paper³ ; assuming a workforce in pubs and bars of 53,500 of which half were permanent staff; assuming that all of the workforce was exposed 100% of the time over a 6-hour shift to 3 times more smoke than would a non-smoker at home living with a smoker; and assuming that all the workers in those places were non-smokers. The review paper from which the relative risks were drawn did not claim precise predictions but only a guide dependent upon many assumptions and unknowns. The researcher’s assumptions were highly speculative, but the estimate suffers from a much larger flaw - the assumption that a relative risk for a chronic disease, which is the result of prolonged exposure over forty or so years, can be applied to a population group which is much younger (as well as one which also changes jobs frequently), with a consequently much smaller duration of exposure. The incidence of lung cancer, heart disease and stroke, below the age of 40 is very low and the age distribution of workers in the hospitality trade on average is very different from those exposed to ETS at home. As if that were not sufficient, an additional, fundamental error in the data used effectively destroys all possible credibility in the claim that was made.

Even though some may regard the public as being scientifically illiterate and mathematically innumerate, that is not a reason for the public to be misled, simply because of the perceived need to achieve headlines.

How the magnitude of a relative risk should be interpreted

In statistics, the words ‘statistical significance’, or ‘statistically significant’, have nothing to do with the magnitude of a measured difference. Statistical significance does not imply real life significance. It is a probability statement of the likelihood that the results did not occur by luck or chance if the groups were really alike; about how certain it is that the results are not a fluke.

Traditionally, conventionally and historically, a RR is considered to be statistically significant – not a fluke - when at a 95% CI it does not include 1.0, albeit that the choice of the value of 95% CI is arbitrary.

A RR finding of around 3.0 is generally considered necessary in order to establish cause. For example:

“The association between cancer occurrence and exposure to either extremely low frequency (ELF) or radiofrequency (RF) fields is not strong enough to constitute proven causal relationship, largely because the relative risks in the published reports have seldom exceeded 3.0…”⁴

A RR of 2.0 or less is generally regarded as being weak and not indicative of a causal association.. The nearer the RR to 1.0, the more likely is this to be the case:

“…relative risks of less than 2.0 are considered small and are usually difficult to interpret … Such increases may be due to chance, statistical bias, or effects of confounding factors that are sometimes not evident.”⁵ .

“…when the relative risk lies between 1 and 2 . . problems of interpretation may become acute, and it may be extremely difficult to disentangle the various contributions of biased information, confounding of two or more factors, and cause and effect.”⁶

“Until the 1980s, epidemiologists were concerned mainly with relative risks that exceeded about 1.5 and were often much higher. Many controversies now centre on much lower risks, a notable example being the effect of ‘passive smoking’ on lung cancer risk. The pooled data show a statistically significant effect, and all studies are consistent with a relative risk of about 1.3 (US National Research Council, 1986). In view of the many difficulties discussed above, however, it can plausibly be argued that such small effects are beyond the limits of reliable epidemiological inference (particularly for lung cancer, in which the major cause produces large relative risks), as smoking habits may be inaccurately recorded and are correlated with many other social and occupational factors, including the smoking habits of spouses. A number of spurious associations with relative risks for lung cancer of this order might thus be found in a large enough sample. The observations that short-service workers in various industries suffer elevated risks for lung cancer, which seem unlikely to be caused by their recorded occupational exposure, further illustrates the problem.”⁷

Yet, in the case of lung cancer and ETS, a 1997 meta-analysis⁸ accepted by the UK authorities found a RR of 1.26 (95% CI 1.06 – 1.47), derived amongst non-smokers living and not living with smoking spouses. That has been claimed to be a "substantial" excess risk and one warranting bans on smoking in work and public places. That is simply not correct.

In 1992, the US EPA found a RR of 1.19 for lung cancer associated with ETS. However, that was only statistically significant at a 90% CI; it was not significant at 95% CI at which it included 1.0. Nonetheless, in 1998 that report was used as a basis for listing ETS as a known human carcinogen.

IARC’s 1998 report⁹ was a case-control study of lung cancer and exposure to ETS in 12 centres from 7 European countries that the researchers claimed provided “the most precise available estimate of the effect of ETS on lung cancer risk in Western European populations.” It reported no overall statistically significant increase in risk of lung cancer from ETS in any of the situations where people were exposed to ETS. The conclusions of the study stated:

“Our results indicate no association between childhood exposure to ETS and lung cancer risk (0.78 (95% CI 0.64-0.96)). We did find weak evidence of a dose-response relationship between risk of lung cancer and exposure to spousal (1.16 ( 95% CI 0.93-1.44)) and workplace ETS (1.17 (95% CI 0.94-1.45)). There was no detectable risk after cessation of exposure.”

In other words, not only were relative risks found to be low, but at the 95% Confidence Interval they included 1.0, indicating that they were not statistically significant. The following observation was also made in the report:

“The available literature on ETS exposure from the spouse and lung cancer is large. However, only six studies are available from Europe; two of them, conducted in Greece, showed a twofold increase in risk for women ever married to a smoker. Of the other studies, one from Scotland provided very unstable risk estimates of the same magnitude as the Greek studies and two – one from the UK and the other from Sweden – provided little evidence of an association.”

The results were within the range at which the IARC itself concluded that unequivocal results may be forever unachievable. Yet after negative reporting of the results by the media, IARC insisted that the findings “add substantially” to previous evidence of the risk between ETS and lung cancer. A WHO press release then implied that the results proved a link between ETS and lung cancer, a highly problematic conclusion given their own guidelines of epidemiological best practice¹⁰ .

It is difficult to see how it could be claimed that the study adds substantially to the case against ETS and much less does it prove a link between ETS and lung cancer. The interpretation of such weak evidence is not in line with the official interpretation of very similar findings of other supposed health risks.

For example, a major study¹¹ of the supposed link between electric power lines and childhood leukaemias produced a RR of 1.24, with a 95% Confidence Interval of 0.86 - 1.79. The researchers concluded that this provided “little evidence” of a link between power lines and leukaemia. The US National Cancer Institute went further, declaring that the study showed magnetic fields “do not raise children’s leukaemia risk”.

Another study¹² of women with breast implants found a RR for hospitalisation for connective tissue disorders of 1.3 with a non-significant 95% CI of (0.7 – 2.2), again close to the IARC passive smoking study. But whereas the IARC findings were claimed to prove a link between ETS and lung cancer, in the breast implant study they were found not to be associated “with a meaningful excess risk of connective tissue disorder”¹³ .

What is absent is an explanation as to why the low RRs that have been reported in respect of lung cancer and ETS - with 95% CIs often including 1.0 and any excess risk capable of being accounted for by only modest degrees of bias and confounding, or by inadequate statistical adjustment for such factors - are regarded by some as providing incontrovertible proof of a causal link. And also why the interpretations of ETS RRs are not in line with the general guidance provided in 1998 by the Government in answer to a Parliamentary question, albeit incorporating an incorrect explanation of a CI:

“Relative risk provides a measure of the strength of association between a factor and an illness. It is an important way of measuring increases or decreases of risk over time or between different groups by comparing the incidence of an illness or hazard within a population to some baseline (for example, if drinkers are twice as likely to suffer from a particular disease as compared with the general population, a factor of 2 may be cited). A stronger association of greater than 2 is more likely to reflect causation than is a weaker association of less than 2 as this is more likely to result from methodological biases or to reflect indirect associations which are not causal. The significance of any such number does though need to be considered in context and from a number of viewpoints.

First, there is a statistical significance: in other words, what confidence is there in the number itself. This will depend on the quality and extent of the available data. Scientists usually express these by giving a confidence interval: rather than by saying that the relative risk factor is 2, they will say that (for example) one can be 95 per cent certain that it lies between 1.6 and 2.4.

Even when the strength of an association is precisely determined, it is insufficient in itself to confirm a direct causal link between possible cause and illness. The strength of an association is only one of several criteria which must be considered in the assessment of causation. Other criteria include:

the cause must precede the effect;

the biological plausibility of the association - is the association consistent with other knowledge e.g. experimental evidence?

the consistency of the finding – is the same result obtained from different studies using different methodologies elsewhere?

the presence of a “dose-response” relationship – an increased response to the possible cause being associated with an increased risk of developing the illness.

All these factors would be taken into account in trying to pinpoint cause.

The practical significance of risk factors, also needs to be considered and depends on how great is the underlying risk. Doubling a very small probability (risk), say 1 in 10,000,000, still results in only a very small risk of illness. Doubling a risk of, say, 1 in 100 could, depending on its nature, be more serious.

In practice, scientific judgments will be made and debated on a case-by-case basis. The Government can draw on the expertise of independent scientific advisory committees which are constituted to provide balanced judgment on the questions covered above”¹⁴ .

The factors mentioned in that important Parliamentary answer are included in the criteria that were proposed by Bradford Hill¹⁵ to guide the evaluation of a body of evidence as to whether or not an association between an outcome and a putative risk factor is causal. In the case of ETS, the study findings do not come close to meeting the Bradford Hill criteria for causality. In particular, they are not consistent, generally produce very weak or no excess risks, and rarely show dose-responses.

The nature of ETS

ETS is a mixture of the smoke released from the burning end of a cigarette (termed “sidestream” smoke) and the smoke exhaled by the smoker between puffs¹⁶ . This smoke quickly mixes with the ambient air and becomes highly diluted and, as a result, there are important differences between the level and the chemical and physical composition of the “mainstream” smoke inhaled by the smoker and ETS.

In all normal circumstances, ambient air contains a large number of substances, whether or not smoking has taken place¹⁷ . Such substances can include dust, pollen, bacteria, fungi, trace chemicals from vehicle emissions and other sources of pollutants, as well as, in certain circumstances, emissions from cooking and heating appliances. Research suggests that the types of substances found in indoor air are generally similar, with or without the presence of ETS¹⁸ .

It is extremely difficult to measure real-life ETS. The concentrations of the various substances that make up ETS are generally extremely low and many of the chemicals present in ETS are, irrespective of ETS, likely to be present in the air anyway, emanating from other sources. Moreover, ETS is a complex and constantly changing mixture, making it difficult to extrapolate total ETS exposure from the measurement of an individual chemical marker.

Nonetheless, the results of studies seeking to quantify exposure suggest that concentrations of chemicals in ETS are typically much lower than permissible exposure limits to these chemicals approved by regulators¹⁹ . Studies have, not surprisingly, also reported that non-smoker exposure to ETS is a great deal lower than the smoker’s exposure to mainstream smoke. Generally such studies have looked at exposure to nicotine, not because airborne nicotine is widely thought to cause lung cancer, heart disease or respiratory disease, but because it is almost unique to tobacco smoke and can be measured even at low concentrations.

For example, one study²⁰ reported that, on average, in the course of a year, non-smokers had an exposure to airborne nicotine which was less than the amount delivered to a smoker by just five cigarettes with a yield of 1mg per cigarette. Another study²¹ of British women exposed to ETS in various settings reported that on average a non-smoker would only be exposed to the equivalent nicotine of smoking a single cigarette over a period in excess of two years.

A variety of studies which have measured the biological metabolites of nicotine have suggested ETS exposures of an average of 0.2% to 0.4% of active smoking, while estimates of particulate exposure suggest a factor of around 0.05% to 0.1%.

Measuring uptake, as compared with exposure, of ETS by non-smokers presents its own problems. The most commonly used markers are nicotine and its metabolite cotinine, which can be analysed in body fluids. Subjects do vary, however, in the rate at which they metabolise nicotine. Nicotine and cotinine are also not quantitative markers for other components of ETS. Most scientists also accept that there is a threshold for carcinogenesis and other disease processes²² .

The findings on the nature of ETS suggest that no firm conclusions can be drawn on the possible health effects of ETS without adequate supporting evidence from clinical, experimental and epidemiological studies.

A listing of ETS epidemiological studies

In the tables that follow, there are listings of ETS epidemiological studies concerning lung cancer and ETS, prepared for the TMA by the epidemiologist, P N Lee. With regard to heart disease, studies relating to the work place are listed. Further details relating to the composition of these lists, and also further detailed listings regarding heart disease, are available on the website, www.pnlee.co.uk. The overviews of the findings of those studies given below have been prepared by the TMA.

Lung cancer

There have been over 60 epidemiological studies of lung cancer among life-long non-smokers. The overall evidence shows no statistically significant increased risk of lung cancer in relation to ETS exposure from parents in childhood, or in social situations or to non-spousal ETS exposure at home. The overall evidence shows that lung cancer risk among non-smoking women is associated with having a husband who smokes (and vice versa but an even weaker association). However, this excess risk of well below 2.0 may be accounted for by bias and failure to take account of confounding factors and misclassification. Those studies that reported stronger associations did not adjust for age, a standard procedure to avoid bias. 80% of the studies showed no statistically significant association with smoking by the spouse and lung cancer. The largest five studies (with over 400 lung cancer cases) produced inconsistent results; one reporting a small increase in risk, three no statistically significant increase and one a statistically significant decrease in risk.

Of those studies, around 50 have examined the incidence of lung cancer in women who claim never to have smoked, but who are married to smokers (“spousal” studies), or the nearest equivalent index, such as living with a smoker. Many have reported a small increase in risk, but a significant majority have not reported overall statistically significant increases. Where a statistically significant association was reported, the magnitude of relative risk reported was so small (below 2.0) that it would generally be regarded as being too weak by normally accepted epidemiological standards to form a basis for public health policy²³ .

The small increase in risk reported by various studies could be accounted for by a number of factors. For example, non-smokers living with smokers tend to have different lifestyles and diets from those living in non-smoking households. It is also not possible to be certain that all studies made appropriate adjustments for misclassification – such as when self-reporting non-smokers are in fact former or current smokers. This is especially problematic because former and current smokers not only have an increased risk of lung cancer, they are also more likely to have married smokers and thus be included among those exposed to ETS in these studies.

The data on ETS exposure at work is even less conclusive than the spousal data. Only a very small minority of the studies on ETS and lung cancer have reported an overall statistically significant increase in risk. Similarly, most studies which have looked at ETS exposure in social settings and during childhood do not report an overall statistically significant increase in risk of lung cancer.

Coronary heart disease

There have been around 30 studies of heart disease and ETS among life-long non-smokers. The overall evidence does not indicate an increased risk of heart disease due to ETS exposure in the work place. Only one study out of 18 reported a statistically significant association. Again the weak associations found between spousal smoking are generally not statistically significant and could be accounted for by lifestyle confounding factors – of which over three hundred have been reported – study design, absence of confirmation of diagnosis, and misclassification. Two of the most substantial pools of data on this subject are the databases of the American Cancer Society’s Cancer Prevention Study and the database of the US National Mortality Followback Survey. Analyses of these data sets have reported no overall association between ETS and heart disease²⁴ .

A further large study of ETS and heart disease was published in 2003²⁵ and also showed no increase in risk.

A report of the US Surgeon General²⁶ noted “because smoking is but one of the many risk factors in the aetiology of heart disease, quantifying the precise relationship between ETS and this disease is difficult”.

Children

There is a large body of research on ETS exposure and respiratory disorders in children. These are difficult to analyse overall as there is great disparity in study design, age ranges and subjects, the symptoms measured and methods of diagnosis. There are quite a number of reports of statistically significantly increased risk of respiratory disorders in pre-school age children exposed to ETS. It is unclear to what extent this increase is influenced by other factors more statistically common in smoking households, such as poor diet, housing conditions and quality of pre-natal care. The pattern of increased risk is not consistently replicated for children of school age, suggesting that a real effect, if one exists, is short term and is age-related.

Although smoking by parents has been associated in some studies with an increased risk of “cot death” (sudden infant death syndrome), a long list of other factors has also been reported²⁷ . Some recent studies have reported that incidence of ‘cot death’ has been reduced by up to 50% where parents have followed government advice not to put their children to sleep in a prone position. However, no one yet fully understands the reasons or mechanisms behind this syndrome. Some have suggested that there may be some residual effects of a mother’s smoking during pregnancy, in respect of which there is strong public health advice to women not to smoke during pregnancy.

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