Review for 10.1186/1471-230X-1-6 (2001)

Reviewer's□report 
□Physicians'□Preference□Values□for□Hepatitis□C□Health□States□and□Antiviral□Therapy:□A□Survey□ Title: 
Authors: 
Raj□Patil□( rpatil@ameritech.net )
Scott□J□Cotler□( scotler@rush.edu )
Geraldine□Banaad-Omiotek□( ginabans@hotmail.com )
Robert□A□McNutt□( Robert_McNutt@rush.edu )
Michael□D□Brown□( mbrowngi@media1.com )
Sheldon□Cotler□( scotler@condor.depaul.edu )
Donald□M□Jensen□( djensen@rush.edu )
□1□ □19□Jun□2001 Version: Date: 
□Dr□Robert□Fontana Reviewer: 
□A□paper□whose□findings□are□important□to□those□with□closely□related□research□interests Level□of□interest: 
□Unable□to□decide□on□acceptance□or□rejection□until□I□see□revised□version Advice□on□publication: 
The□authors□conducted□a□survey□using□utility□analysis□of□practicing□physician□preference□of□hepatitis□ 
C-related□health□states,□side□effects□of□antiviral□therapy,□and□threshold□for□recommending□antiviral□ treatment.□The□majority□of□participants□were□primary□care□physicians□attending□a□CME□course.□ 
1.Study□population-□The□authors□state□that□113□physicians□completed□the□survey.□How□many□were□asked 
to□complete□it□(i.e.□response□rate)?□Any□demographic□differences□between□respondents□and□ 
non-responders?□How□many□specialists□such□as□gastroenterologists□or□infectious□disease□doctors□ attended□the□conferences□and□what□was□their□response□rate□?□This□should□be□evaluated□to□exclude□ 
respondent□bias.□In□addition,□when□were□the□surveys□administered□(i.e.□dates)?□This□may□be□a□factor□in□ 
the□level□of□physician□awareness□and□attitudes□towards□treatment.□ 2.□Survey□administration-□When□was□the□survey□given□to□physicians□in□relationship□to□the□CME□activity?□ Before□or□after□?□If□the□survey□was□given□following□presentations□on□viral□hepatitis,□the□survey□results□ 
may□have□intrinsic□bias.□ 
3.□Health□states-□Why□did□the□investigators□define□100%□as□"life□without□hepatitis□C"□as□opposed□to□ 
"healthy□state"?□By□creating□the□scale□as□they□did,□physicians□would□inevitably□chose□a□lower□utility□score□ 
for□someone□with□asymptomatic□hepatitis□C□even□if□they□did□not□have□any□physical□symptoms□or□ 
impaired□quality□of□life.□ 
4.□Definitions□of□health□states-□The□authors□state□the□descriptions□of□health□states□were□based□on□a□prior□ study□and□an□expert□panel□of□hepatologists.□Although□the□defined□states□represent□a□continuum□of□health 
states□frequently□seen□in□hepatitis□C□patients,□the□uninformed□reader□is□unaware□of□the□relative□likelihood 
of□certain□aspects□of□each□described□health□state.□For□instance,□in□HS1□thru□HS3□patients□may□develop□ 
cirrhosis□but□the□more□important□issue□is□how□likely□this□event□is□to□occur□and□therefore□the□desirability□to□ 
be□in□each□state.□Presumably□HS1□patients□would□have□minimal□fibrosis□on□biopsy□and□be□expected□to□ 
have□prolonged□survival□with□minimal□symptoms□but□this□is□not□clearly□defined□to□the□reader.□In□addition,□ 
despite□multiple□studies,□the□histological□severity□of□chronic□liver□disease□has□never□been□shown□to□ 
correlate□with□clinical□symptoms□or□quality□of□life□scores.□It□may□have□been□more□appropriate□to□define□ 
disease□states□based□upon□histology□and□likelihood□of□developing□other□complications.□Please□comment. 
5.□Correlations-□There□were□no□correlations□between□ratings□of□side□effects□of□therapy□and□treatment□ 
thresholds.□This□is□somewhat□surprising□since□one's□enthusiasm□for□recommending□treatment□would□be□ expected□to□be□related□to□their□assessment□of□side□effects□as□well□as□efficacy.□Please□comment.□Is□it□ 
possible□no□correlation□was□seen□due□to□the□fact□that□78%□of□the□respondents□had□never□treated□hepatitis 
C□and□therefore□were□not□able□to□make□informed□assessments?□This□may□explain□the□large□variation□in□ 
physician□rating□of□treatment□side□effects□that□was□observed.□Would□this□study□have□been□more□useful□if□ conducted□in□a□large□group□of□physicians□who□treat□hepatitis□C□patients□compared□to□non-treating□ 
physicians□(GI□vs□PCP)□?□Please□comment.□ 
6.□Discussion-□The□authors□fail□to□mention□an□important□reference□on□Health□Profile□Preferences□of□ Hepatitis□C□patients,□by□Treadwell□et□al□in□Dig□Diseases□and□Sciences□2000;□45:345-350.□In□that□study,□ hepatitis□C□patients□preferred□to□expedite□rather□than□postpone□intervals□of□poor□health□independent□of□ 
the□outcome.□This□study□should□be□mentioned□in□the□discussion□and□how□it□relates□to□physician□ 
preferences.□Other□psychological□factors□including□infectivity,□worry□over□future□health,□and□personal/□ financial□concerns□may□be□of□particular□importance□in□hepatitis□C□patients.□ 7.□Conclusions-□The□authors□summarize□their□findings□in□a□succinct□manner□Some□of□the□limitations□and□ 
pitfalls□of□this□study□mentioned□above□should□be□discussed.□The□respondent□rate□and□potential□for□bias□ 
by□the□environment□in□which□the□survey□was□administered□should□be□mentioned.□In□addition,□an□ explanation□as□to□why□physicians□recommended□a□60%□sustained□virological□response□rate□to□justify□ treatment□should□be□discussed.□ 
Discussion□ 
Chronic□hepatitis□C□(CHC)□is□a□common□disease□in□the□United□States□affecting□over□3□million□people.□ 
The□majority□of□CHC□patients□are□asymptomatic□and□have□compensated□liver□disease.□However,□a□ minority□of□patients□are□at□risk□of□developing□progressive□fibrosis□leading□to□cirrhosis,□liver□failure,□and□ liver□cancer.□The□current□and□future□estimated□health□care□costs□associated□with□the□management□of□ 
CHC□are□substantial.□Combination□IFN□and□ribavirin□therapy□for□6□to□12□months□is□associated□with□a□ 
sustained□virological□response□rate□of□40%□at□6□months□post-treatment.□However,□combination□therapy□ is□also□very□expensive□and□associated□with□a□multitude□of□side□effects□that□lead□to□early□discontinuation□ in□up□to□20%□of□patients.□ 
Although□published□prospective□studies□have□not□demonstrated□improved□survival□or□long□term□clinical□ 
outcomes□in□sustained□responders,□improvements□in□liver□histology□and□quality□of□life□(QOL)□have□been□ 
demonstrated.□QOL□assessments□of□CHC□patients□and□the□impact□of□treatment□on□QOL□are□of□great□ 
importance□in□the□economic□analyses□of□the□management□of□CHC.□In□particular,□QOL□assessments□may 
influence□the□projected□effectiveness□and□cost-effectiveness□of□antiviral□therapy□for□CHC.□ 
Two□perspectives□on□QOL□are□important;□the□patients□and□the□providers.□Patients□frequently□consider□ 
factors□other□than□the□length□of□life□in□making□decisions□regarding□their□care.□Providers□views□on□QOL□ 
may□influence□the□therapeutic□options□they□offer□to□patients.□Furthermore,□physicians□may□frequently□ view□QOL□of□a□given□health□state□differently□than□the□patients□with□the□disease.□Utility□measures□make□a□ unique□contribution□to□the□measurement□of□QOL□and□assessment□of□health□care□interventions□because□ 
they□are□anchored□by□a□scale□of□death□(0)□to□full□health□(1).□Utility□analyses□provide□a□quantitative□ 
estimate□of□the□value□that□people□place□on□a□given□health□state.□Utility□measures□such□as□the□HUI-Mark□ 2/3□allow□a□direct□comparison□of□the□loss□of□quality□adjusted□life□years□across□patients□with□varying□ disease□states.□However,□most□utility□measures□have□been□used□for□patient□assessment□rather□than□ 
provider□assessment.□However,□as□mentioned□physician□views□of□QOL□of□disease□states□and□ 
interventions□are□important□since□they□may□influence□the□therapeutic□options□that□a□physician□ 
recommends□or□offer□to□their□patients.□In□particular,□primary□care□physician□assessment□of□QOL□may□ 
determine□if□a□treatment□plan□or□referral□to□a□subspecialist□occurs.□ 
In□this□study,□physician□utility□ratings□for□health□states□were□inversely□proportional□to□disease□severity□as□ 
expected.□This□observation□helps□validate□the□wording□of□the□disease□state□descriptions.□The□authors□ 
noted□that□practicing□physicians□required□a□higher□SVR□(60%)□before□recommending□anti-viral□treatment□ 
than□is□currently□achieved.□This□finding□is□not□surprising□since□most□physicians□believe□in□the□Hippocratic 
oath□of□"do□no□harm".□In□general,□physicians□would□select□a□treatment□with□the□least□toxicity□and□greatest□ 
efficacy.□Most□physicians□would□only□recommend□treatment□with□a□very□toxic□therapy□if□their□patients□ 
were□suffering□from□a□severe□or□life-threatening□illness□or□likely□to□experience□substantial□benefit□(Risk□vs 
Benefit).□In□the□case□of□CHC,□most□patients□are□asymptomatic,□have□a□normal□physical□exam,□minor□ 
laboratory□abnormalities,□and□prolonged□survival□in□asymptomatic□or□minimally□symptomatic□health□ 
states.□Therefore,□it□is□not□surprising□that□most□physicians□would□want□a□high□efficacy□with□a□toxic□ 
therapy□such□as□IFN□and□ribavirin.□However,□patients□may□feel□differently.□The□study□of□Treadwell□et□al□ suggests□that□CHC□patients□would□much□rather□expedite□periods□of□poor□health□rather□than□delay□them.□ Other□factors□such□as□a□desire□to□reduce□infectivity□and□transmission□to□others□may□be□an□important□ 
factor□in□treatment□choices□in□CHC□patients.□In□addition,□the□demographics□of□CHC□in□the□US□ 
demonstrate□that□the□majority□of□patients□are□middle□aged□and□frequently□middle□class□individuals□with□a□ remote□history□of□illicit□drug□use.□Many□of□these□people□are□actively□employed□and□have□substantial□ 
personal,□family,□and□financial□obligations.□Therefore,□they□may□be□particularly□motivated□to□tolerate□toxic 
therapy□for□a□long-term□health□gain.□Lastly,□fear□of□potentially□untreatable□cirrhosis□or□liver□cancer□which□ 
could□be□prevented□or□delayed□may□be□a□strong□motivator.□ 
The□lack□of□correlation□of□utility□scores□with□physician□speciality□or□experience□with□anti-viral□treatment□is□ 
likely□due□to□the□small□number□of□participants.□ 
The□low□rating□of□side□effects□by□respondents□may□be□in□part□be□due□to□a□lack□of□knowledge□of□the□ frequency□of□each□of□the□side□effects.□For□instance,□in□RCT□of□IFN□and□ribavirin,□25%□of□patients□ reported□difficulty□sleeping□while□70%□complained□of□headache□and□fatigue.□ 
Competing□interests: 
None□declared.