Regulations of cholesterol lowering management and drug use in Denmark 1960-present.

Bjarke Oxlund, associate prof. Sofie Rosenlund Lau, phd fellow Department of Anthropology

The Rise of Statins

28/11/2016 1

Agenda

• Anthropology and regulatory sciences (BO)

• Ongoing study on the uptake of statins in Denmark (SRL) • Background

• Methodology

• Findings

• Regulation at the borders of practice, science and politics

28/11/2016 2

The Anthropology of Medicine

• Anthropologists view medicines as social (over biological effects)

• Anthropologists view regulation as a matter of role distribution and designation (sacred and profane)

• Anthropologists view ”evidence” as a context specific version of knowledge (world view)

28/11/2016 3

Foundational works

28/11/2016 4

”Materia medica” (p. 3)

Anthropologists ”take medicines as the material things of therapy. But we propose to see them as things with social lives; we are more concerned with their social uses and consequences, than with their chemical structure and biological effects.”

28/11/2016 5

What are medicines? (p. 5)

1. Medicines are substances

2. Medicinal substances have powers to transform

3. Transformative powers can be put to different

purposes

4. Medicines can be simultaneously noxious and

beneficial

5. Medcines are used intentionally to achieve an effect

in some body

28/11/2016 6

Questions we ask…

• How did the medication of xxx come about?

• What is the knowledge base behind it?

• Who is granted the power to authorize the treatment?

• Who eventually makes the decision?

• Who supports the decision maker(s)?

• What are the costs incurred (financially, socially,

psychologically)?

• How is the treatment represented in the larger public?

• When and why do changes happen?

28/11/2016 7

Medical anthropology & Science and Technology Studies (STS)

28/11/2016 8

The ‘statin-epidemic’

• International/US history: (e.g. Marks 1997; Greene 2007)

• 1913: Anitschkow demonstrated atherosclerosis in rabbits

• 1950-60s: several Diet-Heart studies

• 1984: Results of the LRC-CPPT (cholestyramine)

• 1987: FDA approves lovastatin

• Pharmaceuticalization (e.g. Abraham 2010)

• ‘The process by which social, behavioural or bodily conditions are treated or deemed to be in need of treatment, with medical drugs by doctors or patients’

• ‘Regulatory-state ideology’

28/11/2016 9

The cholesterol controversy

28/11/2016 10

Rise in the uptake of statins in Denmark

28/11/2016 11

0

50.000

100.000

150.000

200.000

250.000

300.000

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

1,0

00

DD

D

Source: www.medstat.dk

Production of evidence Regulation Standard of care Health necessity (Sharon Kaufman;2015)

The Rise of Statins: How the dispute between

protagonists and antagonists of cholesterol management played out in Denmark

• Lau, Sofie Rosenlund – Ph.d. Candidate, Department of Anthropology

• Andersen, John Sahl – Ass. Professor, The Research Unit for General Practice

• Dela, Flemming – Professor, Xlab – Department of Biomedical Sciences

• Fjelding-Larsen, Katrine – Master Student, Roskilde University

• Oxlund, Bjarke – Ass. Professor, Department of Anthropology

28/11/2016 12

1. What are the key events, knowledge and actors in the socio-historical outline of cholesterol management and statin uptake in Denmark?

2. How can the socio-historical outline be analysed in relation to clinical, political and scientific disputes over preventive medicines in general and cholesterol management and statin use in specific?

Methods

28/11/2016 13

Analysis

28/11/2016 14

• Ludwik Fleck (1935): ‘thought collectives’ • Sheila Jasanoff (1987+1995): interplay between science and politics • Stefan Timmermans and Marc Berg (2003): Latour-inspired work on

standardization

28/11/2016 15

Table1:Milestonesmap

GLOBAL LOCAL

Timeperiods Scientific Clinical/Political Scientific Clinical/Political

Pre-1959 Upuntilmid40satherosclerosisisperceivedasaninevitablepartofageing.Thepathologyofatherosclerosisandheartdiseasedoesnotappearinthe

medicalliteraturebeforelate1940sandisnotwidelyacceptedbeforeearly1960s.

1913:AnitschowandChalatowfindacorrelationbetweencholesterol-fedrabbitsandatherosclerosis–findingsarecontested

1948:TheFraminghamHeartStudymakesthefoundationforariskfactorapproachtoCVD.Firstresultsarepublishedin1957

1946:Intheclassictextbook‘QuantitativeClinicalChemistry’isstatedthatcholesterolonlyplaysacontributoryroleintheproductionofatherosclerosis.(Steinbergp.4)

1957:AncelKeyspublisheshisresultsontheSevenCountriesStudy

Experimentation1960-1986

Thecorrelationbetweencholesterol-richdietandheartdiseaseisstronglydebated.Amethodologicalturnbeginningalreadyinthe50schangesknow-ledgeproductionawayfromexperimentalstudiestopopulation-basedcohortstudiesandseveraldiet-hearthypothesis-testingstudiesareinitiatedespeciallyinthe70swithresultspublishedinthe80s.Eventhoughtthefindingsarehighlycontested,theassociationbetweenreducingcholesterolandloweringtheriskofCVDseemsestablishedbythemid80sandseveralcholesterol-reductioncampaignsareplanned.Statinsareinthepipeline.

1965-70:WHOClofibratestudy1970:Gothenburgpopulationstudy

1971-74:WHOHeartDiseasePreventionProject1971:LipidResearchClinicsCoronaryPrimaryPreventionTrial(LRC-CPPT)isinitiated1972:MultipleRiskFactorInterventionTrial(MRFIT)

1961:AmericanHeartAssociationstartsitsfirstcholesterolcampaign

1981:WHOpublishesthereport:‘Preventionofcoronaryheartdisease’includingbothahigh-riskandpopulationstrategy1984:USconsensusconferenceonloweringbloodcholesterol

Mid80s:severalpubliccampaignsaimingat‘cholesterolnumberawareness’areinitiated.Pharmaceuticaltreatmentsareinitiatorypromoted.

1960:EricWarburgestablishestheDanishSocietyofCardiology1964:TheGlostrupPopulation

Trial1970CopenhagenCityHeartStudy1976TheØsterbroInvestigation

1962:TheDanishHeartFoundationisestablishedwithEricWarburgasthemainfigure

1970s:TheHeartFoundationintroducesaprofoundfocusonexercise,smoking,hearthealthydiet1984:Firstnationalpolicyonhealthydiet

1986:Industry-policycollaborationresultinwarningsoncigarettepackets1986:Clarifyingreportonthe

managementofhyperlipidemia1986:Nationalconsensus-conferenceoncholesterol

1976:AkiraEndodiscoversHMG-CoAinhibitors:themechanismofactionforstatins

1984:TheNationalCholesterolEducationProgramisestablished1985:BrowandGoldsteinreceivesNobelPrizefortheirdiscoveryoflipoproteins

28/11/2016 16

Contestation1987-1997

Ascientificreasoningforloweringcholesterolseemsestablished,yetcliniciansandpoliticiansarestillnotconvincedonthetherapeuticregime;dietchangeshavenotprovedconvincingresultsandpharmaceuticalsareingeneralbadlytoleratedandwithseveralseveresideeffects.Likewise,thetargetgroupforcholesterolreducinginterventionsishardlycontested.Still,publicpreventioncampaignsareinitiatedandstatinsslowlygainground.

1994:LaunchingofthefirstresultsoftheScandinavianSimvastatinSurvivalStudy(4S)(secondarypreventionwithsimvastatin)–laterreferredtoas‘thestatinera’(Steinberg)

1995:WestofScotlandCornoaryPreventionStudy(WOSCOPS)(primarypreventionstudywithpravastatin)1996:CholesterolandRecurrentEventstrial

(CARE)(secondarypreventionwithpravastatin)

1987:FDAapprovesthefirststatin;lovastatin1987:USA+UKeachpublish

theirfirsttreatmentguidelinesoncholesterolmanagement

1987:ThelipidgroupunderDSCisestablished1989:Generalpractitionersare

self-willinglyconductingRCTsoncholesterolreduction1990:TheDanishMedicinesAgencyapprovessimvastatin

Mid90sUffeRavnskovpublishesaseriesofarticlescontestingtheevidenceforstatins

1987:ThefirstCVDscreeningtoolistestedwithintheframeworkofTheDanishHeartAssociation

1988:FirstNationalCholesterolCampaign1990s:CVDmortalityinDenmarkisdecreasing–severaltakesthe

credit1996:DCSpublishtheclarifyingreport:‘Thedyslipidemicpatient’

1989:ThomasMoorepublishes‘TheCholesterolMyth’-seriesinAtlanticMonthly

1994:FirstEuropeanTaskforceonCVDprevention

Routinisation1998-2011

Withtheintroductionofthestatinsandconvincingresultsfromespeciallythe4S-study,cholesterolmanagementbecomearoutinizedpartofclinicalpractice.Saleofstatinrisestremendously.Moreresearchispublishedonthebenefitsofthestatins.Thepharmaceuticalindustryisnowthemostprofitablebusinessinseveralcountries.Thevoiceoftheopponentstocholesterolreductionisattenuated.

2002:PROSPERstudy(Pravastatininelderlyinterventiontrial)2002:MRC/BHFHeartProtectionStudy(simvastatininterventionirrespectiveoncholesterollevel)

2002:TheInternationalNetworkforCholesterolSceptics(THINCS)isestablished2003:JUPITERTrial(Rousuvastatinprimaryinterventiontrial)

2001:CerivastatiniswithdrawnfromtheUSmarketduetohighratesofreportedrhabdomyolysis2003:ThirdEuropeanTaskForce

onpreventionofCVD–introducingSCORE(loweringofthreshold)2004:UKapprovesover-the-countersellof10mgsimvastatin

Ravnskovpublishesseveralbooksandpaperscontradictingthelipidhypothesis(e.g.TheCholesterolMyths2002,IgnoretheAwkward2010).Thebooksaretranslatedintoseveral

languages.

1998:Firstnationalclinicalguidelinesforgeneralpractice1998:Reimbursementrulesareloosened

1999:Precardriskassessmenttoolislaunched.2002:Simvastatinpatentexpiry2002NewDSAMguideline–introducingSCORE

2012-present Despitethesaleandprescribingofstatinshaveincreasedtremendously,thedebateoncholesterolmanagementcontinuesespeciallyinregardtostatinsideeffects.Atthesametime,thereimbursementrulesareloosenedfurther,andnewfeesforpreventiveservicesingeneralpracticeareintroduced.

2011Cochranereviewofprimaryprevention

withstatins–revisedin20132013JohnAbramsonandcolleaguespublishareviewinBMJcontradictingtheCochraneReview

2016:SixthEuropeanTaskForce 2016:Newguidelinesinthe

making..

Important events of 1998

28/11/2016 17

Practice

Politics Science

Regulation of pharmaceuticals at the borders of..