•
`
`pri l 15, 1997, Vol. 156, No. 8 , Le 15 avril 1997, Vol. 156, n° 8
`
`First-line treatment of seasonal (ragweed)
`rhinoconjunctivitis: a randomized management
`trial comparing a nasal steroid spray
`and a nonsedating antihistamine
`E.F. Juniper, G.H. Guyatt, P.J. Fm·ie, L. E. Griffith
`Suicide among Manitoba's aboriginal people,
`1988 to 1994
`B. Nlalch_y, 11-1. W E1111s, T.K. Young, B.J. Co:r
`
`f ,
`,
`I ,
`)I< "'.I S
`First-line treatment of hay fever: %at is the
`best option?
`S. 0 . Freedman
`Bronchiolitis obliterans and wood-burning stoves
`J.C. Hogg
`A sheep named Dolly
`L. Turner
`
`\l < "'
`)l
`•
`Bioethics for clinicians: 10. Research ethics
`C. We[jer, B. Dickens, E.?vl. i'vleslin
`
`Teaching m edical students how to b reak bad news
`,-/_ Garg, R. Buckuum, Y Knso11
`Fatal falciparum malaria in Canadian travellers
`A. Humar, S. Sbarma, D. Z outmnn, K. C. Kni11
`Bronchiolitis obliterans in a man who used his
`wood-burning stove to burn synthetic construction
`materials
`D. T. Ja11igm1, T. Kilp, R. ivlichael, ].]. McC!eave
`Medical education must make room for student(cid:173)
`specific ethical dilemmas
`J St. Onge
`
`•E
`"
`!
`1t
`"If you think it hurts now ... "
`D. Needham
`
`1123
`
`1133
`
`1141
`
`1147
`
`1149
`
`1153
`
`1159
`
`1165
`
`1171
`
`1175
`
`1179
`
`~
`u.
`C
`
`~ (/) a:
`~
`~
`~
`Achoo! Responding
`to ragweed hay fever
`pages 1123 & 1141
`
`FuLL TABLE OF CONTENTS I NSIDE• TABLE DES .MATIERES INTEGRALE A L'INTERIEUR
`
`ASSOCIATION
`M~DICALE
`CANADIENNE
`
`CANADIAN
`MEDICAL
`ASSOCIATION
`
`

`

`IN THIS ISSUE • D ANS CE NUMERO
`Editor's preface
`1101
`Mot du redacteur en chef
`1103
`News and analysis • Nouvelle, et analyses
`1107
`letters • Correspondance
`111 5
`OTC drugs ,,. Sex ratios .,. Patient
`autonom y
`111t CPP and mental disabilities
`,.,. Breast cancer .. Residency-exchange
`programs • Radical mastectomy •
`Malaria • Record keeping • Fee-for-
`service practice in M anitoba • Smoking
`in Japan
`
`Many Canadians suffer from hay fever triggered by ragweed
`pollen. In this issue (page 1123) Elizabeth Juniper and col(cid:173)
`leagues offer some guidance in selecting a first-line treatment by
`comparing the effect of 2 d ifferent types oi medication on
`patients' quality of life. In an accompanying editorial Samuel
`Freedman (page 1141) looks at the variety of medications avail(cid:173)
`able and the need for an indiv idualized approach to treatment.
`
`Un grand nombre de Canadicns souffrent de la fievre des io ins
`causee par le pollen de l'herbe a poux. Dans cc numero (page
`1123), Elizabeth Juniper et ses collegues comparent les effets de
`2 types de medicaments sur la qualite ce vie des patients pour
`conseiller un traitement de premiere ligne. Dans !' editorial
`accompagnant !' article (page 1141 ), Sarruel Freedman examine
`les d ivers medicaments offerts et parle de la necessite de per(cid:173)
`sonnaliser le traitement.
`
`First-line treatment of seasonal
`(ragweed} rhinoconjunctivitis:
`a randomized management trial
`comparing a nasal steroid spray
`and a nonsedating antihistamine
`E.F Juniper, G.H. Guyatt, PJ. Ferrie,
`L.E. Griffith
`
`Suicide among Manitoba's
`aboriginal people, 1988 to 1994
`B. Malchy, M. W Enns, TK Young,
`B.J. Cox
`
`E
`
`r-
`
`First-line treatment of hay fever:
`'What is the best option?
`S. 0. Freednum
`
`Bronchiolitis obliterans
`and wood-burning stoves
`J.C. Hogg
`
`A sheep named Dolly
`L . Tt1rner
`
`Bioethics for clinicians:
`10. Research ethics
`C. Weijer, B. Dickens, E.M. Meslin
`
`Teaching medical students
`how to break bad news
`A. Garg, R. Bucf..."1'/tan, Y. Knson
`
`Fatal falciparum malaria
`in Canadian travellers
`rl.. Humm; S. Shmwia, D. Zoutman,
`KC. Kt1in
`
`Bronchiolitis obliterans in a man
`who used his wood-burning stove
`to burn synthetic construction
`materials
`D. T Janigan, T Ki.Ip, R. Michael,
`J.J. McCleave
`
`1123
`
`1133
`
`1141
`
`"l 1147
`
`1149
`
`1153
`
`1159
`
`1165
`
`l 1171
`
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`

`

`■
`
`April 15, 199i, Vol. 156, No. I • Le 15 .nril 199i, Vol a&, n" I
`
`'
`
`CMAJ Mission Statement
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`
`.Medical education must make room
`for student-specific cthicaJ dilemmas
`1175
`]. St. Onge
`
`"If you think it hurts nuw ... "
`D. Xeedh,1111
`
`1179
`
`J, 1
`
`T ~11· t
`
`,.
`
`I
`
`Getting drugs to where they're needed- Researchers in Varcouver are
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`
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`
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`FtAll il ', e CHF.(J ,/1) t'S
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`C. Grny
`Negative health care enviro11ment
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`DEATHS •
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`ECROLOGIE
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`1247
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`PL l'i[ • ~( ,(()(,~ \,W,,[
`Are medical students ready to make
`career choices?
`Les c tudiant:s en medecinc sont:-ils
`prets a faire un choix de carriere?
`
`1248
`
`Many people use wood(cid:173)
`burning stoves, but burning
`the wrong materials can be
`hazardous. One serious health problem,
`bronchiolitis obliterans, is featured in a case
`report (page 1171) and d iscussed in an
`accompanying editorial (page 1147).
`
`l Indica1cs linked articles/ indique qur les articles portent
`sur le mcme sujet
`
`ISS1' 0820-3946 156 t8I IQ<J:' 124811997
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`lcMAJ-JAMC 1
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`_ ________ Editor's preface I
`
`Fran<;:ais a la page suivantc
`
`T he misery of seasonal allergies
`
`was first described in 1565 by
`the Italian anatomist Leonardo Bo(cid:173)
`tallo, physician to the rich and power(cid:173)
`ful and to an unfortunate person who
`could not tolerate roses. T his "rose
`fever" was described in 19th-cenrury
`England as "summer catarrh," and
`culprits ranging from sunshine to
`ozone to grass pollen were suspected.
`In 1871 an asthmatic physician,
`Charles Blackley, gave credibility
`to the pollen theory when a self(cid:173)
`admin istered skin test elicited a
`strong reaction. By trapping air(cid:173)
`borne pollen on kites flown at 500 m
`he demonsm1ted how far-ranging the
`allergen can be. H e advised evasive
`action: spend the summer on a yacht'
`A more feasible approach is to re(cid:173)
`lieve the symptoms of hay fever ,vith
`medication. Given the wide range of
`prescription and over-the-counter
`remedies available, how should
`physicians approach first-line treat(cid:173)
`ment? In this issue (page 1123) Eliza(cid:173)
`beth Juniper and colleagues report
`on their randomized management
`study of terfenadi..ne, a nonsedati.ng
`antihistamine, and fluticasone, a
`nasally administered topical steroid.
`They found no significant difference
`in benefit between starting treatment
`with terfenadine and adding flutica(cid:173)
`sone as required, and starting with
`fluticasone and adding terfenadi.ne as
`required. Samuel Freedman (page
`1141) responds to these findings by
`noting the recent move by the US
`Food and Drug Administration to
`withdraw approval for terfenadine
`(because of its rare but life-threaten(cid:173)
`ing card.iotoxic effects). He suggests
`starting therapy with dmgs that are
`safer than terfenadioe and cheaper
`
`than both terfenadine and flutica(cid:173)
`sone.
`
`Aboriginal people in Canada arc 3
`to 4 times more likely to comm.it sui(cid:173)
`cide than nonaboriginal people. Brian
`Malchy and colleagues (page 113 3)
`report that from 1988 to 1994 suicide
`rates in ;.\1anitoba were almost 7
`times higher among aboriginal ado(cid:173)
`lescents than among nonaboriginal
`adolescents, and that there were strik(cid:173)
`ing differences between these groups
`in help-seeking behaviour. Their
`study represents an important first
`step in addressing a serious public
`health problem.
`
`Many of us in this country h ave
`wood-buming stoves. Although their
`most evident hazard is accidental fire,
`using these stoves to bum inappropri(cid:173)
`ate materials can also have devastating
`results. David J anigan and colleagues
`(page 1171) describe the case of a man
`who had been renovating his family
`room and decided to bum scrap build(cid:173)
`ing materials in his wood-burning
`stove. vVithin hours he was taken to
`hospital with. bronchiolitis obliterans.
`The authors review the toxicity of
`combusted building materials and
`poin t out that the presence of life(cid:173)
`threatening fumes is not always sig(cid:173)
`nalled by smoke. James Hogg (page
`1147) reviews the pathology of bron(cid:173)
`chiolitis obliterans and provides us with
`stunning photomicrographs. - JH
`
`Reference
`
`I.
`
`\\'a Iron J, Barondess JA, Lock S, editors. O.,fonl
`111,·diml co,11pm1io11 . Oxford (UK): Oxford L' ni,·e r(cid:173)
`sity Press; I 99-!.
`
`CAN MED ASSOC J • APR. 15_,_1_9_9_7;_1_5_&_(_8_) _________ 11_0_1
`
`© 1997 Canadian Medical Association
`
`

`

`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`First-line treatment of seasonal
`(ragweed) rhinoconjunctivitis
`
`A randomized management trial comparing
`a nasal steroid spray and a nonsedating
`antihistamine
`
`Evidence
`
`Et:udes
`
`From the Department of
`*Clinical Epidemiology and
`Biostatistics and tMedicine,
`McMaster University Health
`Sciences Cenn·e, Hamilton,
`O nt.
`
`This article has been peer
`reviewed.
`
`Can Med A.ssoc J 1997;1 %:11 23-3 1
`
`Elizabeth F. Juniper,* MCSP, MSc; Gordon H. Guyatt, *t MD, MSc;
`Penelope J. Ferrie,* BA; Lauren E. Griffith,* MSc
`
`Abstract
`
`Objective: To determ ine whether better health-related quality of life (HRQL) is
`achieved by initiating treatment of seasonal (ragweed) rhinoconjunctivitis (hay
`fever) with a nasal steroid (fluticasone) backed up by a nonsedating antihista(cid:173)
`mine (terfenad ine) or whether it is better to start with the antih istam ine and add
`the nasal steroid when necessary.
`Design: Randomized, nonblind, pa rallel-group management study during the
`6 weeks of the ragweed po llen season in 1995.
`Patients: Sixty-one adults w ith ragweed pollen hay fever recruited from patients
`who had participated in previous clinica l stud ies and from those w ho responded
`to notices in the local media.
`Setting: Southern Ontario.
`Interventions: Nasal steroid group: 200 µg of fluticasone nasa l spray when needed
`(up to 400 µgld) starti ng about 1 week before the ragweed pollen season and con (cid:173)
`tinued throughout, with 1 to 2 tablets of terfenad ine daily (maxim um 120 mg/d) if
`needed. Antih istamine group: 1 60-mg tablet of terfenad ine w hen needed (maxi(cid:173)
`mum 120 mg/d) starting about 1 week before the ragweed pollen season and con(cid:173)
`ti nued throughout, with 200-400 µg/d of fluticasone nasal spray (maximum 400
`µg/d) if needed.
`Outcome measures: HRQL before, at the height of and toward the end of the rag(cid:173)
`weed pollen season; H RQL was measu red using the Rh inoconjunctivitis Qua I ity
`of Life Questionnaire.
`Results: Overal l, HRQL tended to be better in the group of patients whose first-line
`treatment was with fl uticasone (p = 0.052), but the difference between the 2
`groups was smal l and not cl inically important. Just over half (52% [16/3 11 ) of
`the patients in the fluticasone group did not need additional help w ith terfen(cid:173)
`adine, whereas on ly 13% (4/30) of those in the terfenadine group did not need
`additional help with fluticasone (p = 0.002).
`Conclusions: There is little difference in the therapeutic benefit bet\,veen the 2 ap(cid:173)
`proaches for the treatment of ragweed pollen hay fever. Therefore, the approach
`to treatment should be based on patient preference, convenience and cost. Re(cid:173)
`gardless of the treatment, at least 50% of patients will need to take both types of
`medication in combination to control symptoms adequately.
`
`Resume
`
`Objectif: Determiner si l'on ameliore la qualite de vie liee a la sante par un traite(cid:173)
`ment in itia l de la rhinoconjonctivite (fievre des fains) saisonniere {herbe a poux)
`aux stero'fdes par voie nasa le (fluticasone) appuye par un antihistam inique non
`sedatif (terfenadine), ou s' il est preferable de commencer par l'antih istam inique
`et d'ajouter les stero'ides par voie nasale au besoin.
`Conception : Etude randomisee, non a l'insu, de traitement en groupe paral lele au
`cours des 6 semaines de la saison du pol len de l'herbe a poux en 1995.
`
`CA MEIJ ASSOC) • APR. 15, 19'l_7:_1_56_:_(8'-) ____ ___ 1_12_3
`
`© 1997 Canadian Medical Associ.llion /teJ>.t and abstrac;t/res,m,e/
`
`

`

`Juniper, Guyatt, Ferrie, et al
`
`Patients : Soixante et un adultes souffrant de fievre des fa ins causee par le pollen
`de l'herbe a poux et recrutes parmi les patients qui avaient participe a des
`etudes cliniques anterieurs et parmi les personnes qu i avaient repondu a des
`avis dans les medias locaux.
`Contexte : Sud de !'Ontario.
`Interventions : Sujets traites aux stero'i'des par voie nasale : 200 µg de fluticasone
`en vaporisateur nasal au besoin (jusqu'a 400 µg/j) a compter d'environ 1 se(cid:173)
`maine avant la sa ison du pollen de l'herbe a poux et pendant toute la saison, et
`1 ou 2 comprimes de terfenadine par jour (maximum : 120 mg/j) au besoin.
`Groupe traite aux antihistaminiques : un comprime de 60 mg de terfenadine au
`besoin (maximum : 120 mg/j) a compter d'environ 1 semaine avant la saison du
`pollen de l'herbe a poux et pendant toute la saison, ct de 200 a 400 µg/j de flu
`ticasone en vaporisateur nasal au besoin (maximum : 400 µg/j).
`Mesures des resultats: Resultats 1·e latifs a la qualite de vie liee a la sante avant la
`saison du pollen de l'herbe a poux, en plein coeur de la saison et vers la fin de
`celle-ci. Les resultats ont ete mesures au moyen du questionnaire sur la qualite
`de vie liee a la rh inoconjonctivite.
`Resultats: Dans !'ensemble, les patients traites d'abord a la fluticasone avaient ten(cid:173)
`dance a avoir une meilleure qualite de vie (p = 0,052), mais l'ecart entre les 2
`groupes etait faible et sans importance sur le plan clinique. Un peu plus de la
`moitie (52 % [16/31]) des patients traites a la fluticasone n'ont pas eu besoin deter(cid:173)
`fenadine supplementaire, tandis que 13 % (4/30) seulement de ceux qui ont ete
`traites a :erfenadine n'ont pas eu besoin de fl uticasone supplementaire (p = 0,002).
`Conclusions : II y a peu de difference sur le plan des avantages therape utiques en(cid:173)
`tre Jes 2 methodes de traitement de la fievre des foins causee par le pollen de
`l'herbe a poux. II faudrait done choisir le mode de traitement en fonction de la
`preference du patient, de la commodite et du coOt. Peu importe le traitement,
`au moins SO% des patients devront prendre les 2 medicaments combines pour
`bien controler les symptomes.
`
`A t least 2 5% of adults report experiencing seasonal al(cid:173)
`
`lergic rhinoconjunctivitis (hay fcver),1 and despite
`efficacious over-the-counter drugs about 20% of the
`population seek help from their primary care physicim1.2
`Hay fever not only produces troublesome symptoms, it also
`impairs normal daily activities and productivity.1
`-;
`A large number of clinical trials have demonstrated the
`individual efficacy and safety of fast-acting, nonsedating
`antihistamines and inhaled nasal steroids for the treat(cid:173)
`ment of hay fever. A much smaller number of randomized
`trials have compared antihistamines with nasal steroids.6-11
`Although in most of the comparison srudies the results
`tended to favour the latter, the artificial environment of
`the t1ials (regular and sustained daily use p lus double(cid:173)
`dummy techniques to achieve blinding) bears little resem(cid:173)
`blance to how patients use these medications in real life.
`It is impossible to determine from all of these srudies
`whether it is better to start n·eatment with an antihista(cid:173)
`mine and add a nasal steroid for unconn·olled symptoms
`or whether the nasal steroid should be used first, with the
`antihistamine used as back-up.; vVe therefore performed a
`management (effectiveness) srudy to determine whether
`adults ·with ragweed pollen hay fever would acllieve better
`health-related quality of life (HRQL) by starting treat-
`
`1124
`
`CAN MED ASSOC I • 15 AVR. 1997; 156 (8)
`
`mcnt with f:luticasone propionate nasal spray and adding
`terfenadine tablets when needed, or whether they would
`benefit more by starting treatment with tcrfcnad ine
`tablets and adding f:luticasone nasal spray when needed.
`
`Methods
`
`Patient population
`
`vVe recruited 61 adults (aged 17-66 years) &-om south(cid:173)
`em Ontatio who had either participated in previous cfuli(cid:173)
`cal studies or had responded to notices n1 the local media.
`The enuy criteria were as follows: a diagnosis of seasonaJ
`allergic rhinoconjunctivitis; troublesome nasal symptoms
`requiring medication during the ragvveed pollen season
`the previous year; positive skin-prick test result to ragweed
`pollen extract (wheal greater than 3 mm with 2 5 000
`Noon units); no perennial rhinoconjunctivitis (allergic or
`nonallergic) requiring t:reaonent; no chronic nasal obsn11c(cid:173)
`tion, polyposis or snrnsitis; no history of allergen injectioh
`therapy during the previous 12 months; and no history of a
`se1ious illness that might impair quality of life. Pregnant
`and nursing mothers were excluded, as were patients ,vith
`other illnesses requiring treannent with antihistamines or
`
`

`

`oral steroid therapy and those who could not communi(cid:173)
`cate in English. All patients agreed to remain in the rag(cid:173)
`weed pollen area (southern Ontario) for the duration of
`the study. Participants signed an informed consent fo1m
`that had been approved by the Ethics Committee of the
`McMaster University Health Sciences Centre.
`
`Study design
`
`We used a randomized, nonblind study design to com(cid:173)
`pare the 2 treatment regimens over a 6-week period that
`encompassed the ragweed-pollen season in 1995. Before
`the start of the season each patient underwent duplicate
`skin-prick tests with 10-fold serial dilutions of ragweed
`pollen extract (2 .5 to 25 000 Noon units) and single dilu(cid:173)
`tions of extracts of mixed grass pollen (prevalent in the
`month before the ragweed season) and of the fungal
`spores Alternaria and Cladespori11111 (present during the
`first half of the ragweed season in southern Ontario). Sen(cid:173)
`sitivity to the extract in each skin-prick test was estimated
`from the mean of 2 wheal diameters, measured at right
`angles to each other. The estimated sensitivity to the rag(cid:173)
`weed pollen extract was determined from the mean wheal
`diameter of the 5 duplicate skin p1icks.
`Participants were matched into pairs using the follow(cid:173)
`ing criteria in the following order: 1) severity of ragweed
`pollen hay fever during the previous year; 2) skin sensitiv(cid:173)
`ity to the ragweed pollen e..\.'1:ract; 3) skin sensitivity to the
`fungal spore extracts; 4) slcin sensitivity to the mixed grass
`pollen extract; and 5) sex. \Vith the use of a random num(cid:173)
`bers table, 1 patient in each pair was randomly allocated
`to start treatment with the nasal steroid spray and the
`other to start with the antihistamine.
`
`Interventions
`
`1
`
`We provided patients with enough medications for the
`whole ragweed pollen season and gave them both oral and
`written instructions on their optimal use. Vle told all pa(cid:173)
`tients that fluticasone nasal spray is a topical steroid that is
`slower acting than terfenadine but that nasal steroid
`sprays, if applied as soon as symptoms develop, can be
`used quite effectively as needed. 11
`~ "\Ve also told them
`that terfenadine is a fast-acting, nonsedating antihista(cid:173)
`mine. Compliance with the recommended dosing was left
`entirely to the individual patient's discretion. We asked
`patients to use only the medications we provided for their
`hay fever, not to give it to their friends and relatives and
`to contact us if they experienced any troublesome symp(cid:173)
`toms or adverse effects.
`Patients were told which treatment group they were in
`and provided v.~th the medications only after all baseline
`values of the outcome measures had been recorded.
`
`-
`
`Seasonal (ragweed) rhinoconjunctivitis n.
`
`Nasal steroid group
`
`Patients were told that the optimal approach to treat(cid:173)
`ment was to start using 2 puffs ( each puff 5 0 µg) of flutica(cid:173)
`sone nasal spray in each nostril each morning (200 µg/d)
`on Aug. 8, about I week before the start of the ragweed
`pollen season, and to continue with this dosage through(cid:173)
`out the season. They were told that using the nasal spray
`only when needed might result in less effective control of
`their symptoms. We recommended they increase the dose
`to 2 puffs in each nostril tw'ice daily (maximum 400 µg/d)
`if their nasal symptoms became troublesome. If the ~-ymp(cid:173)
`toms continued to be troublesome we ad'lised patients to
`add terfenadine (60 mg) when needed, up to 120 mg/cl,
`and to cut back on the terfenadine once the symptoms
`were controlled.
`
`Antihistamine group
`
`Patients in this group were told that the optimal ap(cid:173)
`proach to treatment was to start using terfenadine on
`Aug. 8 and to take a 60-mg tablet every morning and
`evening (total 120 mg/d) throughout the ragweed pollen
`season. They were told that using less terfenadine might
`result in less effective control of their symptoms. We ad(cid:173)
`vised patients to add fluticasone nasal spray when needed
`(1-2 puffs in each nostril, up to a maximum of 400 µg/d)
`if symptoms became troublesome once they were already
`talcing the 120 mg of te1fenadine daily and to cut back on
`the fluticasone once the symptoms were controlled.
`
`Eye symptoms
`
`vVe provided all patients with naphazoline eye drops
`and recommended that they use 1 drop in each eye when
`needed, up to 4 times per day. Patients who reported
`troublesome eye symptoms in previous years were also
`provided with sodium cromoglycate eye drops and ad(cid:173)
`vised to supplement the naphazoline eye drops with 1
`drop of cromoglycate in each eye 4 times per day until the
`symptoms were conrrollerl.
`
`Asthma
`
`Patients with asthma were instructed to continue tak(cid:173)
`ing their regular asthma medication throughout the
`study. If an inhaled ~-agonist was required every day, we
`recommended 200 µg of beclomethasone di.propionate
`twice daily. If patients had already been prescribed an in(cid:173)
`haled steroid and were needing their ~-agonist daily, we
`recommended increasing the steroid close to that recom(cid:173)
`mended for an exacerbation by the physician treating
`their asthma.
`
`CAN MED ASSOC J • APR. 15, 1997; 156 (8)
`
`1125
`
`

`

`ii Juniper, Guyatt, Ferrie, et al
`
`Outcome measures
`
`Health-related quality of life
`
`Patients were seen 1 week before ragweed pollen was
`expected in the air (the first week of August), at the height
`of the ragweed pollen season (the first week of Septem(cid:173)
`ber) and toward the end of the season (the third week of
`September). At each visit they were asked to complete the
`Rhinoconjunctivitis Quality of Life Questionnaire.i This
`28-item disease-specific instrument is designed to mea(cid:173)
`sme the 7 domains of functional impairment that are
`most important to patients with seasonal allergic rhino(cid:173)
`conjunctivitis: sleep impairment, non-nasal symptoms
`(e.g., headache and fatigue), practical problems, nasal
`symptoms, eye symptoms, activity limitations and emo(cid:173)
`tional function. Patients are asked to consider their expe(cid:173)
`riences during the previous 7 days and to score their de(cid:173)
`gree of impaii-ment on a 7-point scale (0 = not bothered,
`6 = exn·emely bothered). The questionnaire has excellent
`reliability, responsiveness and construct validity and has
`been used successfully in a number of clinical trials over
`the last 6 years. '·1
`1-1~
`
`Medication use
`
`Patients were asked to return all used and unused fluti(cid:173)
`casone bottles and terfenadine packages at the final visit.
`vVe recorded the weight loss from each bottle of flutica(cid:173)
`sone and the number of rerfenadine tablets used. To esti(cid:173)
`mate the number of puffs of fluticasone used by each pa(cid:173)
`tient, we first estimated the mean weight loss per puff by
`weighing a bottle before and after 10 consecutive dis(cid:173)
`charges into the air until the bottle was empty.
`In addition to estimating the actual amount of medica(cid:173)
`tion used by each patient, we calculated the number of
`bottles of fluticasone and packages of terfenadine each pa(cid:173)
`tient would have needed to provide the actual amount of
`medication used.
`
`Statistical analysis
`
`We examined differences between the treatment
`groups using a repeated measures analysis of vari,mce,
`considering p values Less than 0.05 (two-sided) as signifi(cid:173)
`cant. Covariate analysis was used to adjust for differences
`between the 2 groups at baseline. All of the randomized
`subjects were included in the analysis (intention-to-treat
`analysis). The number of puffs of fluticasone used by each
`patient was based on a mean weight per puff of 0.0867 g,
`and the number of bottles of fluticasone that each patient
`needed was based on each bottle containing 170 puffs.
`Terfenadine (Seldane) can be purchased over the counter
`
`1126
`
`CAN MED ASSOC J • 1 5 AVR. 1997; 156 (8)
`
`in Canada in packages of 12, 24 and 36 tablets. After sur(cid:173)
`veying about 10 pharmacies in the Hamilton area, we de(cid:173)
`temuned that the 36-tablet package had the highest sales
`during the ragweed pollen season. Therefore, we used
`this size to estimate the number of packages required by
`each patient.
`vVith sufficient statistical power, even the most trivial
`differences between the treatment groups can reach statis(cid:173)
`tical significance. To interpret HRQL dat'J that reaches
`statistical significance, it is important to know what mag(cid:173)
`nitude of change or difference can be considered clinically
`important. The minimal important difference (MID) is
`defined as "the smallest difference in score in the domain
`of interest which patients perceive as beneficial and would
`mandate, in the absence of troublesome side effects or
`excessive cost, a change in the patient's management."t;
`Using a standardized "anchor-based" method16 we have
`determined that the ;.vIID for the Rhinoconjunctivitis
`Quality of Life Questionnaire is about 0.5 .1• The sample
`
`size for om study was determined on the basis of the
`~ and e1Tor rates of a = 0.05
`.NIID, the pooled variance1
`(two-sided) and~ = 0.1.
`
`1
`1
`~-
`
`•
`
`Results
`
`The profile of the study is summarized in Fig. 1. The
`demographic characteristics and allergy histoiy of the 61
`patients are shown in Table 1. Complete data sets were
`provided by 60 of the patients; the remaining patient, in
`the nasal steroid group, experienced nausea using the flu(cid:173)
`ticasone and asked to be ch,mged to beclomethasone. In
`keeping ,vith the management study philosophy, this was
`permitted, but the patient fai