Table Of ContentOpen Access Research
NICE guidance: a comparative study of
the introduction of the single technology
appraisal process and comparison with
guidance from Scottish Medicines
Consortium
John A Ford,1 Norman Waugh,2Pawana Sharma,3Mark Sculpher,4Andrew Walker5
Tocite:FordJ,WaughN, ABSTRACT
ARTICLE SUMMARY
SharmaP,etal.NICE Objectives: Tocomparethetimelines and
guidance:acomparative recommendations oftheScottishMedicines Article focus
studyoftheintroductionof
Consortium(SMC)andNationalInstituteofHealthand
thesingletechnology - Has the STA process resulted in speedier
ClinicalExcellence(NICE),inparticularsincethesingle
appraisalprocessand guidance forNICE?
technologyassessment(STA)processwasintroduced
comparisonwithguidance - Whatarethedifferencesinrecommendationand
in2005.
fromScottishMedicines timelines between SMCandNICE?
Consortium.BMJOpen Design: Comparative study ofdrugappraisals
2012;2:e000671. publishedby NICE andSMC. Key messages
doi:10.1136/bmjopen-2011- Setting: NICE andSMC. - The STA system has resulted in speedier
000671 Participants: Alldrugs appraisedby SMCandNICE, guidance for some drugs but not for cancer
drugs.
<Prepublicationhistoryfor fromestablishment ofeachorganisation until August
2010,were included.Data weregathered from - SMCpublishes speedierguidance than NICE.
thispaperisavailableonline.
Toviewthesefilesplease publishedreports ontheNICE website, SMCannual - SMC and NICE recommend a similar proportion
of drugs.
visitthejournalonline(http:// reportsand EuropeanMedicines Agency website.
bmjopen.bmj.com). Primary and secondary outcome Strength and limitations of this study
measures:Primaryoutcomewastimefrommarketing - AlthoughsomedifferencesbySMCandNICEare
Received25November2011
authorisation untilpublication of firstguidance. The shown, it is not possible in this study to say
Accepted5December2011
finaloutcomeforeach drugwas documented. Drug which iscorrect.
Thisfinalarticleisavailable appraisalsbyNICE(beforeandaftertheintroductionof - Accuracy of outcome data taken from NICE
foruseunderthetermsof theSTAprocess) andSMCwere compared. website and SMCannualreportsisunclear.
theCreativeCommons Results: NICE and SMCappraised140drugs,415
AttributionNon-Commercial wereappraisedbySMCaloneand102byNICEalone.
2.0Licence;see NICErecommended, withor without restriction, 90%
use of new drugs in England and Wales.
http://bmjopen.bmj.com ofdrugsand SMC80%.SMCpublished guidance
There has been controversy over its deci-
morequickly thanNICE (median7.4 comparedwith
sions, and the timeliness of drug appraisals,
21.4months).Overall, theSTAprocess reduced the
particularly those concerning new cancer
averagetimeto publication comparedwithmultiple
drugs.1e4 NICE does not appraise all new
technologyassessments(median16.1comparedwith
22.8months).However, forcancer medications, the drugs, but only those referred to it by the
STAprocess tooklonger thanmultiple technology Department of Health (DH), after scoping
assessment (25.2compared with20.0months). and consultation.
1HealthServicesResearch
Conclusions: Proportionsofdrugsrecommendedfor In Scotland, the Scottish Medicines
Unit,UniversityofAberdeen,
Aberdeen,UK NHSusebySMCandNICEaresimilar.SMCpublishes Consortium (SMC) appraises all newly
2DepartmentofWarwick guidance more quicklythanNICE.The STAprocess licensed medications (including new indica-
Evidence,Universityof hasimprovedthetimetopublicationbutnotforcancer tions for medicines with an existing license).
Warwick,Coventry,UK drugs.Thelengthier timeforNICE guidance ispartly
The simultaneous functioning of both orga-
3HSRU,Universityof dueto measures toprovide transparency andthe
nisations has been described as ‘comple-
Aberdeen,Aberdeen,UK widespread consultationduringthe NICEprocess.
4UniversityofYork,York,UK mentary’,5butdebateariseswhendifferences
5UniversityofGlasgow, occur because of the implications for the
Glasgow,UK NHS of a drug being provided in England
INTRODUCTION but not in Scotland.
Correspondenceto
DrJohnFord; TheNationalInstituteofHealthandClinical Flow charts outlining the processes are
[email protected] Excellence(NICE)providesguidanceonthe given in figures 1 and 2 (e-version only).
FordJA,WaughN,SharmaP,etal.BMJOpen2012;2:e000671.doi:10.1136/bmjopen-2011-000671 1
NICE, the STA process and SMC
Figure 1 ScottishMedicines
Consortium (SMC) pathway.
Evolution of the NICE appraisal system or modelling. Currently, most new drugs are appraised
Before 2005, the main source of evidence for the NICE under the new STA system, and the TAR-based system
technology appraisal committees was a technology (also called multiple technology assessment (MTA)) is
assessment report (TAR)da systematic review of clinical usedforlargerandmorecomplexappraisals,suchasfor
and cost-effectiveness, usually with economicmodelling, several drugs for the same condition, or, less often, one
produced by an independent assessment group. NICE drug for several conditions.
also received industry submissions including economic The STAsystem issimilar tothat which has been used
modellingbythemanufacturer,andthesewerereviewed by SMC, where the main evidence is an industry
bytheassessmentgroup.Themanufacturerwasgivenan submission,critiquedbySMCstaffwithashortsummary
opportunity to comment on the TAR. The process was of the critique being published with the guidance.
regardedastootimeconsumingandasleadingtodelays During the STA process, an independent academic
in availability of new medications for patients, especially group critiques the industry submission, and the
controversial with new anticancer medications.6 Primary ‘evidence review group’ report is published in full
CareTrustswouldoften not fund new medications until (exceptforcommercialoracademicinconfidencedata)
guidance was produced. on the NICE website, making the STA process more
In 2005, NICE introduced the ‘single technology assess- transparent. In cases where SMC issue guidance on
ment’ (STA) system wherein the main source of evidence a medicine and it is then appraised by NICE using the
for the appraisal is a submission, including economic MTA system, NHS Healthcare Improvement Scotland
evaluation and review of the clinical effectiveness, by the reviewstheNICEMTAguidanceandgenerallyacceptsit
manufacturer, which is critiqued by one of the assess- for use in Scotland, implicitly reflecting an assumption
mentgroups.Thereisnoindependentsystematicreview that the wider scope of an MTA and the extra work
2 FordJA,WaughN,SharmaP,etal.BMJOpen2012;2:e000671.doi:10.1136/bmjopen-2011-000671
NICE, the STA process and SMC
Figure 2 NationalInstituteof
Health andClinical Excellence
(NICE) pathway.ACD, Appraisal
Committee Document;ERG,
Evidence ReviewGroup; FAD,
Final AppraisalDetermination.
involved in the review allowed more evidence to be were defined as ‘recommended (NICE) or accepted
considered and analysis undertaken; the same argu- (SMC)’,‘restricted’or‘notrecommended’,accordingto
ments do not apply to NICE STA guidances and hence classificationinthetablesofappraisalspublishedonthe
they are not used in Scotland. NICE website or SMC annual reports. The term
Therearetwoaimsinthisstudy.First,sinceithasbeen ‘restricted’ can have various meanings, such as place in
6years since the introduction of the STA process by treatment pathway, patient group, or clinical setting. All
NICE, it istimely to assess whether the changehas been medications appraised from the establishment of each
associated with speedier guidance. Second, we compare organisation until August 2010 were included. When
recommendations and timelines between NICE and guidancediffered,weexaminedpossiblereasons,noting
SMC. if the difference was only about restrictions on use,
rather than approval versus non-approval.
METHODS
For all drugs appraised by both NICE and SMC, we RESULTS
calculated the time from marketing authorisation NICE and SMC appraised 140 drugs, 415 drugs were
(obtained from the European Medicines Agency appraised only by SMC and a further 102 only by NICE
website) until publication of guidance. NICE data were (whichstarted3yearsbeforeSMC).Thehighernumber
taken from the technology appraisal guidance docu- appraised by SMC reflects SMC’s practice of appraising
ments on their website. SMC data were extracted from allnewlylicenseddrugs,whereasonlyselecteddrugsare
annualreportsanddetailedappraisaldocuments.Drugs appraised by NICE.
FordJA,WaughN,SharmaP,etal.BMJOpen2012;2:e000671.doi:10.1136/bmjopen-2011-000671 3
NICE, the STA process and SMC
Timeliness: NICE before and after the introduction of STAs Differences in recommendations between NICE and SMC
The main reason that NICE introduced the STA system NICE and SMC appraised 140 drugs, 415 drugs were
was to allow patients, especially those suffering from appraised only by SMC and a further 102 only by NICE
cancer, quicker access to medications. The time from (whichstarted3yearsbeforeSMC).Thehighernumber
marketing authorisation to appraisal publication is appraised by SMC reflects SMC’s practice of appraising
presented in table 1. After 2005, the STA process allnewlylicenseddrugs,whereasonlyselecteddrugsare
reduced the time to publication of guidance. There is appraised by NICE. Of the 140 comparable appraisals,
marked variability in NICE data throughout the years. thesameoutcomewasreachedin100(71.4%),thesame
Forexample,in2009,themediantimetopublicationfor outcome but with a difference in restriction in 27
STAs was 8months (range 4e38), but in 2010, the (19.3%)andadifferentoutcomein13(9.3%). Details of
median time was 29months (range 4e30). However, thedifferences,andpossiblereasons,areshownintable3.
although the STA system has reduced the time from It was found that 90.1% of all medications appraised by
marketing authorisation to issue of guidance (median NICE were recommended, with or without restriction,
16.1, range 4e41months) months compared to 22.8 71.5% were defined as recommended and 18.6% as
(range 2e77)months for MTAs, it has failed to reduce restricted, whereas 80% of medications were recom-
the time for anticancer medications. For STAs of cancer mended by SMC, with or without restriction (39.3%
products, the appraisal process took an average of 25.2 definedasacceptedand41.1%definedasrestricted),as
(range 4e41)months compared with 20.0 (range shown in table 4. (Note that these tables reflect how
2e46)months for cancer-related MTAs. NICEandSMChavecategorisedtheirdecisionsandthey
This increased length of appraisal is also reflected may not be comparable as discussed below.)
within SMC; anticancer drug appraisals take longer However, the differences are often less than these
(median 8.0months, range 1e29) months compared figures suggest because NICE sometimes approves
with 7.3months (range 1e44) for all SMC drugs. a drug for very restricted use. For example, NICE
There was no significant difference between multi- approved pimecrolimus ‘for very restricted use for the
drugandsingle-drugMTAs(median22.8months,range second-linetreatmentofmoderateatopiceczemaonthe
2e77 and 21.5months, range 3e58, respectively). face and neck in children aged 2e16 that has not been
controlled by topical steroids and only where adverse
Timelines: NICE versus SMC effects such as irreversible skin atrophy were likely’d
Comparing all appraised drugs, from marketing fourrestrictionsbyage,site,previoustreatmentandrisk
authorisation to publication, NICE guidance takes of adverse effects. SMC rejected it entirely. Although it
considerably longer, as shown in table 2, at median was recommended by NICE but not by SMC, there may
21.4months, compared to 7.4months for SMC. For be very little difference in the amount of drug used.
drugs appraised by both organisations, NICE guidance The approval rate was lower for cancer drugs
took a median 15.7months longer than SMC guidance. compared to non-cancer ones. NICE appraised 80
In the SMC process, the Detailed Advice Document is cancer drugs, 16 (20%) of which were not recom-
distributedfor1monthtohealthboardsforinformation mended. SMC appraised 98 cancer drugs and 29
and to manufacturers to check factual accuracy. (29.6%) were not recommended.
Table1 SMC andNICE times to guidancebyyear
SMC NICE
Median Range Median Range Median Range Median Range
Year Number (months) (months) Total (months) (months) MTAs (months) (months) STAs (months) (months)
2000 NA 4 14 4e19 4 14 4e19 NA NA NA
2001 NA 4 13 3e17 4 13 3e17 NA NA NA
2002 23 5 1e23 11 18 9e29 11 18 9e29 NA NA NA
2003 57 7 1e30 10 34 7e46 10 34 7e46 NA NA NA
2004 59 8 1e32 13 22 2e35 13 22 2e35 NA NA NA
2005 71 8 1e29 2 11 3e19 2 11 3e19 NA NA NA
2006 94 6 1e44 21 21 6e77 19 21 6e77 2 19 17e20
2007 84 7 1e24 19 26 9e58 9 35 24e58 10 24.5 9e41
2008 72 7 1e30 21 26 2e60 11 36 2e60 10 12.5 5e37
2009 66 7 1e24 21 20 4e46 8 28.5 20e46 13 8 4e38
2010 30 10 1e30 4 29.5 4e35 1 35 NA 3 29 4e30
MTA,multipletechnologyassessments;NA,notapplicable;NICE,NationalInstituteofHealthandClinicalExcellence;SMC,ScottishMedicines
Consortium;STA,singletechnologyassessment.
4 FordJA,WaughN,SharmaP,etal.BMJOpen2012;2:e000671.doi:10.1136/bmjopen-2011-000671
NICE, the STA process and SMC
decision was reached. Publically available material
Table2 Median timefrommarketing authorisation to
includes drafts and final scopes, responses by consultees
guidancepublication
and commentators and a detailed final appraisal deter-
Alldrugs Cancerdrugs
mination. Our impression (two of us have been associ-
Marketing authorisation 7.35(1e44) 8.00(1e29) ated with NICE appraisal for many years) is that the
to SMC, months(range) lengthoftheAppraisalConsultationDecisionsandFinal
Marketing authorisation 21.40(2e77) 23.62(2e46) Appraisal Determination has increased over the years.
to NICE,months(range) More recently, we have noted that drugs may be consid-
Marketing authorisation 16.05(4e41) 25.23(4e41) ered more often by the appraisal committee than the
to STA,months(range) expected two timesdthere are examples of drugs going
Marketing authorisation 22.81(2e77) 20.02(2e46)
to three and four meetings. In the STA process, NICE
to MTA,months(range)
mayissuea‘mindedno’andgivethemanufacturermore
MTA,multipletechnologyassessments;NICE,NationalInstituteof
than the usual interval in which to respond with further
HealthandClinicalExcellence;SMC,ScottishMedicines
Consortium;STA,singletechnologyassessment. submissions. This in turn sometimes leads to the
EvidenceReviewGroupaskingformoretimetoconsider
the new submissions. Hence, drugs may received very
DISCUSSION
detailed consideration, but at a time cost.
The NICE STA process was introduced in 2005, with the
Marked variability throughout the years (table 1) is
intention of producing speedier guidance, especially for
most likely caused by small numbers, especially in 2010,
cancer medication. Our analysis shows that the intro-
where only three STAs are included. Excluding 2010,
ductionoftheNICESTAprocesshasresultedinspeedier
therehasbeenageneraltrendforshorteningSTAtimes
guidance but not for cancer drugs. There are some
and lengthier MTA times. This is unsurprising, since
differences in recommendations between NICE and
more complex appraisals would be assessed in an MTA.
SMC,withSMCrejectingagreatproportionofthedrugs
The longest appraisals (77months for etanercept in
appraised by both organisationsd20% versus 10%.
psoriatic arthritis and 60months for infliximab for
Reason for difference in recommendations ankylosing spondylitis) are explained by the fact that
The reasons for different recommendations might be NICE can appraise older drugs if referred by the DH.
expected to include: Both of these were appraised in an MTA with other
< NICE sometimes allowed cost per QALY exceeding drugs.
the upper bound of its cost-effectiveness threshold SMC publishes considerably fewer details. NICE
(£30000 per QALY); especially after the ‘end-of-life’ appraisal committees deal with two to three STAs per
additional guidance was adopted. However, in several day,allowingforbothpublicandprivatesessions.SMCis
instances, NICE did not report their estimated cost able to deal with six to seven new drugs per day. NICE
per QALY.SMCcanalsoaccept acost perQALYover allows a 2-month period between appraisal committee
£30000 but seems not to do so to the same extent as meetings, 1month for consultation and then a period
NICE. for the evidence review group and the NICE secretariat
< Different timings, sometimes by years, during which to reflect on these comments and produce a commen-
time ‘patient access schemes’, with part-funding tary for the second meeting of the appraisal committee.
by manufacturers, were introduced into NICE Comments on the draft guidance (the Appraisal
calculations. Consultation Decision) come from manufacturers (of
< Themodellingfromthemanufacturerwassometimes drug and comparators), clinical groups such as Royal
different. For example, SMC considered telbivudine Colleges, NHS staff, patients and the general public
to be cost-effective compared to entecavir for the through the consultation facility on the NICE website.
treatment of chronic hepatitis B, but the manufac- Figures 1 and 2 (e-version) demonstrate the pathway of
turer’ssubmissiontoNICEdidnot include entecavir. appraisal for SMC and NICE.
< Evolution of evidence base. There is a trade-off between consultation and timeli-
< Longer appraisals provide more opportunities to ness. The emphasis by NICE on wide consultation,
explore subgroups. Therefore, differences may arise compared to the less extensive approach by SMC, may
between decisions if one organisation has time to simplybeafunctionofsizeofterritory.SMCanditsNew
evaluate numerous subgroups within a population. DrugsCommitteehaverepresentativesfrommosthealth
< The difference in timelines means that if a drug is boards. (Note that in Scotland, trusts have been abol-
rejected by SMC, the manufacturer may be able to ished and NHS boards are unitary authorities providing
revise the modelling before the drug goes to NICE. both primary and secondary care, so representatives
include managers and clinicians). This in effect allows
Reasons for lengthier NICE appraisals consultation as part of the process, though mainly with
The causes for the lengthier process at NICE include NHS staff rather than patients and public. Patient
consultation7andtransparency.NICEproducesaconsid- interest groups have the opportunity to submit written
erably more detailed report and explanation of how the comments to the SMC in support of a new medicine. In
FordJA,WaughN,SharmaP,etal.BMJOpen2012;2:e000671.doi:10.1136/bmjopen-2011-000671 5
NICE, the STA process and SMC
Table3 Differences between NICEand SMC appraisals
NICE product Condition Decisions Reason PAS
Infliximab Crohn’sdisease Recommended SMC (April 2007):manufacturer No
(activeseverein byNICE,not did not presentasufficiently robust
adults) bySMC economiccase
NICE (2010): recommendedinpatients
whohave notresponded toconventional
treatment orhave contraindication to
conventional treatment,until treatment
failure or 12months.The assessment
group estimatedthe ICER tobe£68000
Infliximab Crohn’sdisease Recommended SMC (April 2007):manufacturer’s No
(fistulising) byNICE,not justification ofthe treatment costin relation
bySMC toits healthbenefits wasnot sufficient
NICE (2010): recommendedinpatients
whohave notresponded toconventional
treatment orhave contraindication to
conventional treatment,until treatment
failure or 12months.NICE assumedthe
ICER tobe £30000,soaborderlinecase
Infliximab Acute, severely Recommended SMC: manufacturer did notpresent a No
activeulcerative byNICE,but not sufficiently robusteconomiccase
colitis bySMC NICE:recommendedas apossibletreatment
forpeople with acute,severelyactive
ulcerativecolitis onlyifciclosporin could
not beused.Otherwise shouldbe usedonly
in trials
Infliximab Severe ankylosing Restricted by SMC: in 2004,SMC saidthat the economics No
spondylitis(adults) SMC, not casehad not beendemonstrated.In 2005,it
recommended was approvedforveryrestricted use,asonly
byNICE cost-effective‘when rigorousstopping rules
were applied’.SMC laterchangedadvice in
linewith the NICE MTA
NICE (2008): inan MTA,infliximabwas not
cost-effective, especially comparedwith
etanerceptand adalimumab. SMChad
consideredinfliximabin isolation
Pimecrolimus Atopic dermatitis Recommended SMC: noevidencethatit has clinical No
(eczema) byNICE,not advantagein termsofefficacyor safety
bySMC whencompared with thealternative
treatments andthe economic caseforusing
thispreparationis unproven
NICE:recommendedfor veryrestricteduse
forthe second-linetreatment of moderate
atopic eczemaon thefaceand neckin
children aged2e16yearsthathas notbeen
controlled bytopicalcorticosteroids,and only
whereseriousadverse effectssuchas
irreversible skin atrophylikely
Docetaxel Prostate cancer Recommended SMC: the cost-effectivenesshasnot been No
(incombination (hormone- byNICE,not demonstrated
with steroid) refractory) bySMC NICE:asatreatment optiononlyif Karnofsky
performancestatus scoreis60%or more.
N.BNICE allowed anICER of £33000as
being‘acceptable cost-effective’
N.BSMC havechanged theiradvicein
accordancewith NICE MTA
Continued
6 FordJA,WaughN,SharmaP,etal.BMJOpen2012;2:e000671.doi:10.1136/bmjopen-2011-000671
NICE, the STA process and SMC
Table3 Continued
NICE product Condition Decisions Reason PAS
Cinacalcet Hyperparathyroidism Useveryrestricted SMC: the economiccase wasnot No
(refractory) usebyNICE, not demonstrated
recommended NICE:recommendedfor usein ‘extreme
bySMC situations’:people ondialysis whohave
veryhighlevels ofparathyroidhormone in
theirblood thatcannotbe loweredbyother
treatments andcannot have a
parathyroidectomybecauseof the risks
involved. Itis notclear fromthe guidance
whatthe ICER was estimatedto be,but
in mostsituations, itwas well above£30000
Telbivudine Chronichepatitis B Recommended SMC: approvedon thegroundsthat itwas No
bySMC, not cost-effectivecompared to entecavirand
byNICE lamivudine
NICE:cost-effectivenessnot proven.The
manufacturer’ssubmissiondid not include
anycomparison withentecavir. NICE
commentedthat thecomplexity andlack
oftransparency in themanufacturer’s model
undermined the credibilityofthe economic
results
Pegaptanib Wetage-related Restricted by SMC: approvedforrestricted use inJuly 2006 No
macular SMC, not NICE:deemednot cost-effectivein August
degeneration recommended 2008inan MTAalongwith ranibizumab,
byNICE which wasconsideredcost-effective
N.BSMC havechanged theiradvicein
accordancewith NICE MTA
Sunitinib Advanced and/or Recommended SMC (July2007):manufacturer did not Yes
(first line) metastaticrenal byNICE,but not presentasufficientlyrobusteconomicanalysis
cellcarcinoma bySMC NICE (March2009): approvedforrestricted
usein one subgroup,with firstcycle freeto
NHS, andcost perQALYof £54000 under
the ‘end-of-life’ system
N.BSMC havechanged theiradvicein
accordancewith NICE MTA
Trabectedin Advanced soft Recommended SMC: manufacturer did notpresent a Yes
Intravenous tissuesarcoma byNICE,but not sufficiently robusteconomicanalysis
bySMC NICE:restricted usewith ICER at £34000,
with a‘patient accessscheme’, inwhich
manufacturer fundsthe sixthandany
furthertreatments.Approved under
end-of-life system
Adalimumab Severe active Recommended SMC (October2007):manufacturerdid No
Crohn’sdisease byNICE,but not presentasufficiently robusteconomic
(adults) not bySMC case
NICE (May2010): restricteduse.NICE
did not agreewith the assessmentgroup
assumptionsabout relapseratesand
obtained furtheranalysesfromits Decision
SupportUnit. ThefinalNICE cost perQALY
estimateisnot clear
Continued
FordJA,WaughN,SharmaP,etal.BMJOpen2012;2:e000671.doi:10.1136/bmjopen-2011-000671 7
NICE, the STA process and SMC
Table3 Continued
NICE product Condition Decisions Reason PAS
Efaluzimab Psoriasis Restricted use SMC: cost-effectivenesswas not No
approvedby demonstrated
NICE,not NICE:Maybe atreatment optionifdisease
recommended issevere asdefinedbyatotal Psoriasis
bySMC AreaSeverity Index(PASI) of 10or more
and aDermatologyLifeQuality Index
(DLQI)of >10. The psoriasishas failed
torespondto standardsystemictherapies
includingciclosporin,methotrexateandPUVA;
or theperson is intolerant to,orhas a
contraindication to,thesetreatments and
onlyif theirpsoriasishas failedto respondto
etanerceptor theyareshownto beintolerant
of,orhavecontraindicationsto,treatmentwith
etanercept
N.BThe license hasbeenwithdrawn from
EMAdue toapossible linkwith multifocal
leukoencephalopathy
EMA,EuropeanMedicinesAgency;ICER,incrementalcost-effectivenessratio;MTA,multipletechnologyassessments;NICE,National
InstituteofHealthandClinicalExcellence;PAS,PatientAccessScheme;PUVA,PsoralenandUltravioletLightA;SMC,ScottishMedicines
Consortium.
contrast, NICE serves a population >10 times the size, chair of NICE, has suggested that for NICE to produce
anditwouldnotbepossibleforeveryPrimaryCareTrust guidance within 6months ofmarketing authorisation, it
or trust to be represented on the appraisal committees. needs to begin the appraisal process about 15months
ThewideconsultationbyNICEmayreducetheriskof beforeanticipatedlaunch.8Incontrast,SMCjustlooksat
legal challenge. NICE is probably more likely to be all new drugs, so no selection process is needed. This
challenged than SMC for two reasons. First, NICE guid- also has the advantage of complete clarity for industry
anceisusedmoreasareferenceforpricingnegotiations since they know that if they are taking a medicine
by other countries. Second, NICE guidance is fixed for through the European licensing process, then (when
(usually) 3years, whereas a manufacturer whose medi- successful) they will definitely be expected to provide
cine has not been recommended can re-submit to SMC asubmissionbySMCsotheycanplanforthisatanearly
at any time. stage, whereas at that stage, they may not know whether
Consultation by NICE starts well before the actual it will be referred to NICE.
appraisal, with scoping meetings, and even a consulta-
tion on who should be consulted. After the scoping Reasons for lengthier appraisal for cancer drugs
process,NICEmakesarecommendationtotheDHasto Onepossibleexplanationforlongertimelinesforcancer
whether a drug should be appraised. The DH then drugs is that many are expensive and hence costs per
decides on whether or not to formally refer the drug to QALY may be more likely to be on the border of
NICE. This process takes about 3months (from scoping affordability. Another possibility may be that the
meeting to formal referral). However, this consultation evidencebasefornewcancerdrugsislimitedatthetime
and referral process usually happens before marketing of appraisal, so the cost per QALY may be more uncer-
authorisation and so is unlikely to be relevant to the tain. This represents a challenge to the appraisal
timelines examined in this paper. Sir Michael Rawlins, committee, for example, trying to identify subgroups
and stopping/starting rules. Additional analysis may be
sought from the Evidence Review Group or the manu-
Table4 NICE and SMCfinaloutcome
facturer. All this generates delay.
Final outcome NICE SMC
Recommended, No. 173 (71.5) 218 (39.3) Strengths and weaknesses
of drugs(%) Weincludedonlydrugsassessedthroughthetechnology
Restricted, No.of 45(18.6) 228 (41.1) appraisalprogrammeatNICEandwillhavemissedafew
drugs (%) appraised through the guideline process.9 Appraisal
Not recommended,No. 24(9.9) 109 (19.6) outcomes were collected from published tables on the
of drugs(%)
NICE website or SMC annual reports.
NICE,NationalInstituteofHealthandClinicalExcellence;SMC, One problem is the definition of restricted. We have
ScottishMedicinesConsortium.
mentioned above the pimecrolimus example, which is
8 FordJA,WaughN,SharmaP,etal.BMJOpen2012;2:e000671.doi:10.1136/bmjopen-2011-000671
NICE, the STA process and SMC
defined as ‘recommended’ by NICE but for very faster than biological agents. However, timelines varied
restricted use. Many drugs are recommended by NICE among US providers such as Veterans Affairs and
and SMC for use in specialist care only, but this would Regence.
probably not be regarded as ‘restricted use’ by most Barbieri and colleagues (2009) also reviewed the role
people. On other occasions, NICE has approved drugs of independent third party assessment and concluded
for narrower use than the licensed indications. For that it had advantages but that it tended to take longer,
example, liraglutide and exenatide are licensed for use as found in this study for non-cancer drugs.7 However,
in dual therapy, but NICE has recommended them for they argued that the third party system, as was provided
use only in triple therapy, albeit with a very few excep- to NICE by the academic groups, need not prolong the
tionsindualtherapy.Otherexamplesincluderestriction timelines. Indeed, they suggested that basing the
on the grounds of prior treatment, fitness states and appraisal on manufacturers’ submissions might lead to
blood glucose levels. delays if there had to be an iterative process of
If we adopted a broader definition of restricted, then requesting further data or analyses.
onecouldarguethatthemajorityofNICEapprovalsare
for restricted use. HowmanybodiesdoestheUKneedtoevaluatenewdrugs?
InadditiontoNICEandSMC,therearesystemsinWales
How does this compare to other studies
andNorthernIreland.TheAllWalesMedicinesStrategy
Only a few studies have looked at the differences
Group evaluates new medicines for the NHS in Wales.
between NICE, SMC and the impact of the new STA
However,itaimstoavoidduplicationwithNICE,though
system.7 10 11 In 2007, Dear et al found a different
itmayproduceinterimadvicependingaNICEappraisal,
outcomeinfiveoutof35comparabledecisions(14.3%),
and only assesses up to 32 new medicines a year.
with an average of 12months difference between SMC
In Northern Ireland, there has been since 2006
andNICE.8In2008,Barham11reportedthattheinterval
a system whereby NICE guidance is assessed for suit-
between marketing authorisation and guidance publi-
ability for implementation in the Province, with the
cation was longer for cancer STAs than MTAs. expectation that is normally will be adopted.13 There is
Dear et al also compared time differences between
also a Regional Group on Specialist Medicines, which
SMC and NICE in 2007.10 Based on 35 drugs, they esti-
can issue advice on drugs not appraised by NICE.
matedthetimedifferencebetweenSMCandNICEtobe
The existence of the several bodies making policy on
12months. Our results show the difference to be closer
newdrugsreflectstheimpactofdevolutionandseparate
to 17months based on 88 comparable medications;
development of the NHS in the four territories of the
however, when looking at only STAs, this was approxi-
UK.
mately 12months. Dear et al also found an acceptance Licensing is now carried out on a Europedwide basis
rate of 64% by SMC, although this does not take into
butthatismoreofatechnicaljudgementofefficacyand
account re-submissions. Our data show an acceptance
safety. Health technology assessment of new medicines
rate of about 80%, which probably reflects our use of
takes into account a wider range of factors such as will-
only final SMC decisions, some after re-submissions.
ingnessandabilitytopayforthebenefitsaccruedlocally,
Barbieri and colleagues (2009) reviewed decisions on
definition of value, accountability to local parliaments,
25 cases where NICE and SMC guidances could be
local clinician buy-in and clinical guidelines.
compared and found general agreement in terms of
recommendations for use in 23 cases.7 However, they Conclusions
noted that NICE was sometimes more restrictive than
The introduction of the NICE STA system has been
SMC,forexample,recommendingthatusebelimitedto
associated with reducedtime to publication of guidance
subgroupsbasedonageorfailureofprevioustreatment.
for non-cancer drugs, but for cancer drugs, the STA
They give an example, alendronate for osteoporosis,
timelines are little different from MTA timelines.
approved without restriction by SMC but restricted to
Significant differences remain in timescales between
age and risk status subgroups by NICE. In this case, the SMC and NICE. There are also some differences in
appraisal was done under the previous NICE MTA guidancesbetweentheorganisations,butthedifferences
process involving an independent assessment report by in terms of approved/not approved are often minor,
an academic group. Barbieri and colleagues also noted
such as approved for very restricted use/not approved.
that the interval between SMC and NICE appraisals
FundingNoexternalfunding.
couldbeaslongas2years,whichcouldleadtodifferent
decisions because of an increasing evidence base. CompetinginterestsNone.
Mason and colleagues (2010)12 reported that for the ContributorsJFcarriedoutmostofthedataextractionandanalysis,produced
period 2004e2008, the STA process had not shortened thefirstdraftandistheguarantor.PScarriedoutsomeinitialanalysisand
the timelines compared to MTAs, for cancer drugs, but contributedtodesignoftheanalysis.NWanalysedreasonsforthedifferent
recommendationsintable3,usingpublishedguidances.AWandMS,with
did not examine non-cancer medications. They also
considerableexperienceofSMCandNICEprocesses,respectively,
examined time to coverage in the USA and noted that
commentedondrafts.MSisaformermemberoftheNICETechnology
withincancertherapy,hormonaldrugsbecameavailable AppraisalCommitteeandisalsoamemberofoneoftheacademicgroups,
faster than chemotherapy drugs, which were in turn whichprovideassessmentreports(forMTAs)orevidencereviews(forSTAs).
FordJA,WaughN,SharmaP,etal.BMJOpen2012;2:e000671.doi:10.1136/bmjopen-2011-000671 9
NICE, the STA process and SMC
NWwasamemberoftheNICEACfor5yearsandhasbeenamemberofthree 6. WattsG.Arethescotsgettingabetterdealonprescribeddrugsthan
assessment/evidencereviewgroups.Allauthorscommentedonthefinaldraft. theEnglish?BMJ2006;333:875.
7. BarbieriM,HawkinsN,SculpherM.Whodoesthenumbers?Therole
ProvenanceandpeerreviewNotcommissioned;externallypeerreviewed. ofthird-partytechnologyassessmenttoinformhealthsystems’
decision-makingaboutthefundingofhealthtechnologies.Valuein
DatasharingstatementNodataareavailable. Health2009;12:193e201.
8. RawlinsMD.ThedecadeofNICE.Lancet2009;25:351e2.
9. WaughN,CumminsE,RoyleP,etal.Newerdrugsforbloodglucose
REFERENCES controlintype2diabetes:systematicreviewandeconomic
1. HortonR.NICEvindicatedinUK’sHighCourt.Lancet evaluation.HealthTechnolAssess2010;14:1e248.
2007;18:547e8. 10. DearJ,O’DowdC,TimoneyA,etal.ScottishMedicinesConsortium:
2. CooksonR,McDaidD,MaynardA,etal.NICEmess:isnational anoverviewofrapidnewdrugassessmentinScotland.ScottMedJ
guidancedistortingallocationofresources?BMJ2001;323: 2007;52:20e6.
743e5. 11. BarhamL.SingletechnologyappraisalsbyNICE:aretheydelivering
3. SteinbrookR.Sayingnoisn’tNICEdthetravailsofBritain’snational fasterguidancetotheNHS?Pharmacoeconomics2008;26:1037e43.
Instituteforhealthandclinicalexcellence.NEnglJMed 12. MasonA,DrummondM,RamseyS,etal.Comparisonofanticancer
2008;359:1977e81. drugcoveragedecisionsintheUnitedstatesandUnitedKingdom:
4. RafteryJ.ReviewofNICE’srecommendations,1999-2005.BMJ doestheevidencesupporttheRhetoric?JCO2010;28:3234e8.
2006;332:1266e8. 13. DepartmentofHealth,SocialServicesandpublicSafety.
5. CairnsJ.ProvidingguidancetotheNHS:theScottishmedicines ImplementationofNationalInstituteforHealthandClinicalExcellence
ConsortiumandthenationalInstituteforclinicalExcellence GuidanceintheHPSS.http://www.dhsspsni.gov.uk/
compared.HealthPolicy2006;76:134e43. nice_guidance_01-06.pdf(accessedAug2011).
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