Tobacco Documents Online

r• Annex 2 C t)N.I~ 1 DI's N'L• )al i', CO~,TIIITTI;r ON S;.iOKIr?G ISSUTsS SYORI:.II•.G PAI2'lY ON 1~f~;;DICAL IIFSEAIICII - FIRST h1:PORT I+.:.ES'?'t37? R S Ti I P The Working Party comprises: i Dr. H.R. Bentley Dr. F.G. Colby Dr. D.G. Felton Dr. F .O. Field Dr. H. Gaisch DSr. . C .I3, .L. Iriatchett Dr. K.A. Meloh - I.T.L. (Chairman) - R. J. Reyiiolds - B-A.T. - Gallaher - Philip Morris - Carreras Rothmans - Reemtsma The Working Party met on 2lst/22nd July at Shockerwick liou.se. I IyTTI.i ODUCT I O:`T We first discussed the cojlcept of "causality" in the eont.etit of the I.C.O.S.I. Position Paper which acl•.nowledL;ed the fact that "there is a continuing s,aoki.n~ and health controversy". We recognised that medical and scientific opinion is not unanimous zs to the interpretations to he placed upon the statistical associations between smoking and various diseases. We then considered briefly "all diseases and medical conditions that have been associated vrLtli smol.ing" but decided that in order to i^eet our target ol producing a first repor t by the 1 Ith September ile1t, it r;as necesszr y to exercise our opCion to be ceL~ctive in our coverar e and in the recommendations we might wish to make. Accordingly, \:'e ConC:ellLrated upon IoLU' IIla'iI2 areas of concern and considered tlicsc in the order of priority "~hich we bt::licve<1 to be jus- •t:ii:ied by the exteilt of the deficiences in knoNvled;;e posed by each of them. 1

2 In identifying these gaps in kno'aledtge ~~,,e repeatedly found th«t th^ rlost ir,iport:,jnt immediate need was to review, in deta il, the 1;no,V,,ledt;e each one of us possessed uj: current work now being carried out in the countries 'we represented, whether published or not, in order to discover where new -work ra;i.Z;i3t most usefully be concentrated. l9e decided that this task should be unden ta.ken sepa ratel,y by each one of us prior to a further meeting of the Working Party. Thereafter we considered, in detail, which specific areas cauld most profitable be covered in these reviews. With very few exceptions,-we found that deficiencies in knowledge related to the la ck of research concerning the many other co-variables besides smoking that are statisti- . cally associated with the san.e range of dis eases - most of which are likely to have multi-factorial etiology. The most important of these co-variables are : diet habits (e . g. vitamin intal.e), weight, height, sez, personal history of die.~oascas, average amount of sleep, fitness (e.g. exercise sports), alcohol consumption, medications, drug abu7Z,, personality score, ethnic backgrou.?d, occupat.ion, income, family size, history of diseases within the family, hobbies, marriage/divorce. It quickly became clear to us that the task which we had decided to undertake going to be difficult, at the outsej.;, because of the failure oil the part of all of us i.: recent years to maintain a high and continuous level of communication between the tobacco industries in different parts of the world; and, although this was not covered by our terms of reference, we agreed to recommend that further consideration should be given to the preferred means whereby such co:r.:aunications, in the specific area of knovlecige re- lated to our terms of reference, might be improved. Our conclusions in respect of four areas of research, which we chose to consider, follo;,,, as separate sections. CAPDI G'JASCU7tl1P nx srAsE We concluded that tliere N;rere defects iii kno\%,ledt;e in regard to the multi-factorial nature of two entirely different aspects of carda.ova.sc:u i.rLr disease ti,rhich have been statis ti- cally associated with smohing namely:- 1 T'a^.i:ors Wlri.ch :n1s;ht be immedia te c:~uses of death We concluded tha'L• the current evidence, related as it i.s r.lmu:.;t solely to crude overall r.tortality ratios, had a:n3oraly failed to rccot,;nise the overx•i.di.nr; i.mpo:L•tniice of t11:ing- account of henetic, con,,titlttion;tl nnd soc:i.al vari: b.Les betwc•e:it groups whic:lh hczve cli.i'1'ert ent n.or•talit; t•<c t;io5 . AJ i:ernai.ive

0 J ~ FaCi.ol':~ \',hiC:h be 1it:ii:^Ct7_~1tC (:P..U:~ea of Cleat}1 (con' t) approzches to this problem, better suited to take account of these vari.ables; could, we thousht, include:- a) studies based upon i.ndividuals admitted to hospitals with due care to avoid or allow for the effects on such studies of 'Berksonian' bias ; and further work based upon twins. Such studies might usefully be supported by further work on the pathological and pha.rmacological fac,,;ors tvhich might be involved in immediate causes of death in individuals zritih ca-rdiov:.scular di sease including, for ex:.mple, studies in humans or experinental animals, where appropriate, of : - a) the possible effects of specific chemical co:<<pounds, including constituents of tobacco sraoke, in inducin„ vcntricular fibrillation ; and b) the.bio-chemical mechanisms involved in blood clotti_n;. 2 Factors N--rhich might contribute to the underlyina degenerative changes characteristic of cardio- vascular disease We concluded:- a) that any study based upon hospital a&Assions designed to elicit factors concerned N':ith immediate causes of death might use.i'ully be extended to patients admitted to hospital sufferin--I:rom non-fatal card:i.,-:,c condi.tions, provided that bias could be avoided or its effects allowed for in work with such pntients ; b) that the search for a suitable laboratory al moc'.el for atherosclerosis, although aliii- not at all hopeful, should continue; rV a O N C -..r.

c) that further work related to lipid i:raci,iollisa- tion and Mia:lysis would be useIul ; ancl d) that the factors apparently involved in the causation of strokes were too complicated, at this stage, •to justify affording any priority to this area of research. Sr,iOKIT\TG IN PREGNANCY It was important,•sve thought again, to have regard to gaps in knowledge of the constitutional and social factors associated with difficulties in conception, pregnancy, parturition, lac- tation, pre-natal risks to the foetus and post-natal•risks to off-spring. These gaps in knowledge we thought could most usefully be met by further extensive studies in several dif- ferent countries and over longer periods of time of the type pioneered by the late Professor Yerushalmy in the U.S.A.. We agreed that there was a need further for :- a) additional information on specific factors possibly affecting birth N;,eight ; particularly in relation to carbon monoxide which might profitably be studied in non-siuoking populations environmentally exnosed to the gas, or in studies with laboratory ani_raals ; b) investigation of possible relationships bet;;,een maternal and foetal haemoglobin affinity for carbon monoxicie ; and c) further experimental studies of the role, if any, of nicotine in pregnancy. t RDSPIRATOx?Y DISEASES We concluded that the main gaps in knowledge justifying f ur• ther work were :-- 1 The effect on notional mortality rates of errors in d1 :Ii;nosis . 2 The effects of genetic, constitutional and social f.actors including, for example:- a) more detailed analyses of existing data such as those acquired in U.S.A. by IInmmond and in Sweclen by C.odei•lof ; and

5 b) the possibility of adapting any proposed l~ctiv stt;c:.i ^S , inc1_udi_n.~; f ltn:;c> cn.lle•ci .for in the U.K. by the buidelines of the IIu.ni:.er Cc;.r.mittee to take account of such fa.ctors. 3 The iieed for further epidemiological studies of chari;,•in~ patte~°ns in cazicer type and secular changes in the incidc:nce o f car.Lcer in di f ferent or gans , together with theoretical studies of the relation- ship of dose/rcsponse and time lapse/r esponse data in human populations to theories of carcinogenesis. 4 Studies to show the. extent to which a tendency to respiratory diseases might be heritable. 5 Further work in the,adr,iitted7.y difficult area of devel'opino anirtal models for hui,;an -respiratory diseases as a preliminary to meaningful dose/ response studies of suspected causative insults. After consideration we decided not to recommend further work on : -- Specific industrial or other environmental causes of respiratory diseases; or 2 _identification of specific factors associated wl.th susceptibility e.g. to lung cancer in human populations. It became clear repeatedly throughout our discussions of this topic that much of the work we' had in mind mi#;ht be suited to broadly-based multi-national research projects. We recognised, how,ever, that account wou ] d have to be taken of broader aspects of policy before any further consideration could be given to this possibility. ALLEGED EFFECTS OF S;•iOI:Ii•;G ON I;O':-S',10:OERS We first noted that most moderate authors do not consizier ' passive snioki.nb' to be a danber to the non-smoker' s healtii. \

r-. . ' ..' 1',e agreed t.l?zat there was a need for furtr.,;r quantitative studi.ns ?,jider rca1_iStic condi-tio)?S of the extent to r:lii.ch ciS~'1eCL.t~J C ~ il'C`l tC ,., sraol~e constituents, p;lrti.cu).aily carbon monoxi_de, nicot;ine and, if poSsible, particulate mztt.er, . We noted however that, on f.ItC ui,pl-ovecd assumption that ztiy risks to health that might be associated with such constituents were lincar t.ith no threshold level, there was no pr ospcct of being able to show that non--srnokers were exposed to no risks to health whatsoever from an E.'21vi1.'onJAelit in which tobacco products were smoked. O'I'11TR DISEASES As mentioned in the introduction, we gave no consideration at our fa.x'st; meeting to any other diseases ati•sociated with cigarette smoking. We recognised, nevertheless, it would be necessary to consider at least some of these on future occasions. We have not, in this report, met the requirement of our terms of reference to make recommendations, in regard to areas for fl:rtl:^x rf'S('^ i°c?2, <^.S to how such research }~21;;ht be dolle, where it ~;iivht be undertaken and how it raight be financed. The Working Par ty concluded that, since these matters involve wider issues of policy which might need further discussioii, - fi.hey could be more profitably discussed later after we had moved beyond this prelir:Ti nar. y stage of identifying the more important gaps in 1.nowledL'e. We decided to meet again by the kind invitation of Philip Paorris at Neuchatel on the 5th/6th Decer-nbcr. ------------------------ i IV [d't a ~ a ~ 7,'(ith /1ttr;u-,t, 1977. a ~ ~ _....._ ... .,.- "m, r «~