Human papillomavirus (HPV) vaccine policy and evidence-based medicine: Are they at odds?
|
|
- Britton James
- 8 years ago
- Views:
Transcription
1 Annals of Medicine, 2011; Early Online, Informa UK, Ltd. ISSN print/issn online DOI: / REVIEW ARTICLE Human papillomavirus (HPV) vaccine policy and evidence-based medicine: Are they at odds? Lucija Tomljenovic1 & Christopher A. Shaw 1,2 1 Neural Dynamics Research Group, Department of Ophthalmology and Visual Sciences, University of British Columbia, 828 W. 10th Ave, Vancouver, BC, V5Z 1L8, Canada and 2 Program in Experimental Medicine and the Graduate Program in Neuroscience, University of British Columbia, Vancouver, BC, Canada All drugs are associated with some risks of adverse reactions. Because vaccines represent a special category of drugs, generally given to healthy individuals, uncertain benefits mean that only a small level of risk for adverse reactions is acceptable. Furthermore, medical ethics demand that vaccination should be carried out with the participant s full and informed consent. This necessitates an objective disclosure of the known or foreseeable vaccination benefits and risks. The way in which HPV vaccines are often promoted to women indicates that such disclosure is not always given from the basis of the best available knowledge. For example, while the world s leading medical authorities state that HPV vaccines are an important cervical cancer prevention tool, clinical trials show no evidence that HPV vaccination can protect against cervical cancer. Similarly, contrary to claims that cervical cancer is the second most common cancer in women worldwide, existing data show that this only applies to developing countries. In the Western world cervical cancer is a rare disease with mortality rates that are several times lower than the rate of reported serious adverse reactions (including deaths) from HPV vaccination. Future vaccination policies should adhere more rigorously to evidence based medicine and ethical guidelines for informed consent. Key words: Cervarix, cervical cancer, Gardasil, HPV vaccines, informed consent, vaccine adverse reactions Key messages Todate,theeffcacyofHPVvaccinesinpreventing cervicalcancerhasnotbeendemonstrated,while vaccinerisksremaintobefullyevaluated. CurrentworldwideHPVimmunizationpracticeswith eitherofthetwohpvvaccinesappeartobeneither justifiedbylong termhealthbenefitsnoreconomically viable,noristhereanyevidencethathpvvaccination (evenifproveneffectiveagainstcervicalcancer)would reducetherateofcervicalcancerbeyondwhatpap screeninghasalreadyachieved. Cumulatively,thelistofseriousadversereactions relatedtohpvvaccinationworldwideincludesdeaths, convulsions,paraesthesia,paralysis,guillain Barré syndrome(gbs),transversemyelitis,facialpalsy, chronicfatiguesyndrome,anaphylaxis,autoimmune disorders,deepveinthrombosis,pulmonaryembolisms, andcervicalcancers. BecausetheHPVvaccinationprogrammehasglobal coverage,thelong termhealthofmanywomenmaybe atriskagainststillunknownvaccinebenefits. Physiciansshouldadoptamorerigorousevidence based medicineapproach,inordertoprovideabalancedand objectiveevaluationofvaccinerisksandbenefitstotheir patients. Introduction In2002theUSFoodandDrugAdministration(FDA)statedthat vaccines represent a special category of drugs aimed mostly at healthyindividualsandforprophylaxisagainstdiseasestowhich an individual may never be exposed(1). This, according to the FDA,places significant emphasis on vaccine safety (1). In other words,contrarytoconventionaldrugtreatmentsaimedatmanagement of existing, oftentimes severe and/or advanced disease conditions,inpreventativevaccinationacompromiseineffcacy for the benefit of safety should not be seen as an unreasonable expectation. Furthermore, physicians are ethically obliged to provideanaccurateexplanationofvaccinerisksandbenefitstotheir patientsand,whereapplicable,adescriptionofalternativecourses oftreatment.thisinturnenablespatientstomakeafullyinformed decisionwithregardtovaccination.forexample,theaustralian guidelines for vaccination emphasize that for a consent to be legallyvalid,thefollowingelementmustbesatisfied: it[consent] canonlybegivenaftertherelevantvaccine(s)andtheirpotential risksandbenefitshavebeenexplainedtotheindividual (emphasis added) (2). Likewise, the United Kingdom (UK) guidelines pertainingtovaccinationpracticesstatethatsubjectsmustbegiven Correspondence: Lucija Tomljenovic, Neural Dynamics Research Group, Department of Ophthalmology and Visual Sciences, University of British Columbia, 828 W. 10th Ave, Vancouver, BC, V5Z 1L8, Canada. E mail: lucijat77@gmail.com (Received 24 May 2011; accepted 31 October 2011)
2 2L. Tomljenovic & C. A. Shaw adequateinformationonwhichtobasetheirdecisiononwhether to accept or refuse a vaccine (3). This includes having a clear explanationonvaccinerisksandside effects(3). Surprisingly,intheUnitedStates(US),therearenogovernmentalrequirementsforinformedconsentforvaccination(4).Such anomissionleavesthedooropentoafailuretoobtaininformed consent. Nonetheless, there are regulatory agencies such as the USFDAwhichareempoweredtoassurethatonlydemonstrably safe and effective vaccines reach the market.in addition, health authorities(i.e.uscentersfordiseasecontrolandprevention (CDC)) are expected to provide expert advice concerning the benefitsandrisksrelatedtoparticulardrugs,includingvaccines. Whentheseoffcialbodiesarenotabletoprovidetheirnormal regulatoryoversightand/oriffinancialintereststakeprecedence overpublichealth,significantproblemsintrueinformedconsent guidelinescanoccur. What is known about the currently licensed human papillomavirus(hpv)vaccines?whataretheirbenefits,andwhatare theirrisks?whilemedicalauthoritiesinanumberofcountries, includingtheus,stronglyadvocatetheiruse,somemembersof thepublichavebecomeincreasinglyscepticalforavarietyofreasons.thekeyquestionposedbysuchscepticsisthis:isitpossible thathpvvaccineshavebeenpromotedtowomenbasedoninaccurateinformation?thepresentarticleexaminestheevidencein ordertoanswerthiscriticalquestion. Can the currently licensed HPV vaccines prevent cervical cancer? Gardasil s manufacturer, Merck, states on their website that Gardasildoesmorethanhelppreventcervicalcancer,itprotects against other HPV diseases, too. Merck further claims that Gardasildoesnotpreventalltypesofcervicalcancer (5). Similarly,theUSCDCandtheFDAclaimthat This[Gardasil] vaccine is an important cervical cancer prevention tool thatwillpotentiallybenefitthehealthofmillionsofwomen (6)and Basedonalloftheinformationwehavetoday,CDC recommends HPV vaccination for the prevention of most typesofcervicalcancer (7).Allfourofthesestatementsareat significantvariancewiththeavailableevidenceastheyimply thatgardasilcanindeedprotectagainstsometypesofcervical cancer. At present there are no significant data showing thateither GardasilorCervarix(GlaxoSmithKline)canpreventanytypeof cervicalcancersincethetestingperiodemployedwastooshort to evaluate long termbenefits of HPV vaccination. The longest follow updatafromphaseiitrialsforgardasilandcervarixare 5and8.4years,respectively(8 10),whileinvasivecervicalcancer takesupto20 40yearstodevelopfromthetimeofacquisitionof HPVinfection(10 13).Bothvaccines,however,arehighlyeffectiveinpreventingHPV 16/18persistentinfectionsandtheassociatedcervicalintraepithelialneoplasia(CIN)2/3lesionsinyoung womenwhohadnohpvinfectionatthetimeoffirstvaccination (13 15). Nonetheless, although cervical cancer may be caused by persistent exposure to 15 out of 100 extant HPVs through sexual contact (11), even persistent HPV infections caused by high risk HPVswillusuallynotleadtoimmediateprecursorlesions,letaloneinthelongertermtocervicalcancer.Thereason forthisisthatasmuchas90%hpvinfectionsresolvespontaneouslywithin2yearsand,ofthosethatdonotresolve,onlyasmall proportion may progress to cancer over the subsequent years (10,11,16 18). Moreover, research data show that even higher degrees of atypia (such as CIN 2/3) can either resolve or stabilize over time (19). Thus, in the absence of long term follow updata,itisimpossibletoknowwhetherhpvvaccines can indeed prevent some cervical cancers or merely postpone them.inaddition,neitherofthetwovaccinesisabletoclearexistinghpv 16/18infections,norcantheypreventtheirprogression tocin2/3lesions(20,21).accordingtothefda, Itisbelieved that prevention of cervical precancerous lesions is highly likely to result in the prevention of those cancers (emphasis added) (22).ItwouldthusappearthateventheFDAacknowledgesthat thelong termbenefitsofhpvvaccinationrestonassumptions ratherthansolidresearchdata. Gardasil and Cervarix: do the benefits of vaccination outweigh the risks? Currently,governmentalhealthagenciesworldwidestatethat HPV vaccines are safe and effective and that the benefits ofhpvvaccinationoutweightherisks(6,23,24).moreover, theuscdcmaintainsthatgardasilis animportantcervicalcancerpreventiontool andtherefore recommendshpv vaccinationforthepreventionofmosttypesofcervicalcancer (6,7).However,therationalebehindthesestatementsis unclear given that the primary claim that HPV vaccination preventscervicalcancerremainsunproven.furthermore,in theus,thecurrentage standardizeddeathratefromcervicalcanceraccordingtoworldhealthorganization(who) data(1.7/100,000)(tablei),is2.5timeslowerthantherate ofseriousadversereactions(adrs)fromgardasilreported to the Vaccine Adverse Event Reporting System (VAERS) (4.3/100,000dosesdistributed)(TableII).IntheNetherlands, thereportedrateofseriousadrsfromcervarixper100,000 doses administered (5.7) (Table II) is nearly 4 fold higher than the age standardized death rate from cervical cancer (1.5/100,000)(TableI). Although it may not be entirely appropriate to compare deaths alone from cervical cancer to serious ADRs from HPV vaccines, it should be re emphasized that (in accordance with FDA guidelines) the margin of tolerance for serious ADRs for a vaccine with uncertain benefits needs to be very narrow, especiallywhensuchvaccineisadministeredtootherwisehealthy individuals (1).HPV vaccination, even if proven effective as claimed,istargeting9 12yearoldgirlstopreventapproximately 70%ofcervicalcancers,someofwhichmaycausedeathatarate of /100,000womenindevelopedcountrieswitheffective Pap smear screening programmes (Table I). For a vaccine designedtopreventadiseasewithsuchalowdeathrate,therisk to those vaccinated should be minimal. Further, according to someestimates,hpvvaccinationwoulddolittletodecreasethe alreadylowrateofcervicalcancerincountrieswithregularpap screening(10).thus,anyexpectedbenefitfromhpvvaccination will notably drop in the setting of routine Pap screening. Accordingly, the risk to benefit balance associated with HPV vaccinationwillthenalsobecomelessfavourable.ontheother hand,indevelopingcountrieswherecervicalcancerdeathsare muchhigherandpapscreeningcoveragelow(tablei),thepotentialbenefitsofhpvvaccinationaresignificantlyhamperedby highvaccinecosts(25). Itshouldbenotedthatforanyvaccinethenumberofdoses that are eventually administered is lower than the number of dosesthataredistributed.thus,calculationsbasedonthelatter tendtounder estimatetherateofvaccine associatedadrs(figure 1). Supporting this interpretation, we show in Table II and Figure1thatforanyofthetwoHPVvaccines,thereportedrateof ADRsper100,000dosesadministeredisverysimilaracrossdifferentcountriesandapproximatelyseventimeshigherthanthat
3 HPV vaccines and evidence-based medicine 3 TableI.Keydataoncervicalcancer,HPV 16/18prevalence,andcervicalcancerpreventionstrategiesin22countries.DatasourcedfromtheWorldHealth Organization(WHO)/InstitutCatalad Oncologia(ICO)InformationCentreonHPVandcervicalcancer(105). HPV 16/18 prevalencein Incidenceper Mortalityper Mortalityranking womenwithlow / 100,000women 100,000women amongallcancers high gradelesions/ HPVvaccine Country (age standardized) (age standardized) (allages) Papscreeningcoverage(%) cervicalcancer(%) introduced Australia Netherlands US France Canada Spain UKandIreland Israel Germany China VietNam Russia Brazil Thailand th 16th 15th 15th 14th 15th 16th 14th 13th 7th 4th 7th 2nd 2nd 60.6(Allwomenaged20 69y screenedevery2y) 59.0(Allwomenaged> 20y screenedevery5y) 83.3(Allwomenaged> 18y 74.9(Allwomenaged20 69y screenedevery2y 72.8(Allwomenaged18 69y screenedevery3y;annualifat highrisk) 75.6(Allwomenaged18 65y screenedevery3y 80(Allwomenaged25 64y screenedevery5y) 34.7(Allwomenaged18 69y 55.9(Womenaged20 49y screenedevery5y) 16.8(Allwomenaged18 69y 4.9(Allwomenaged18 69y 70.4(Allwomenaged18 69y 64.8(Allwomenaged18 69y 37.7(Allwomenaged15 44y 3.8/44.6/ /61.6/ /55/ /63.4/ /56.2/ /46.9/ /61.9/ /44.8/ /54.1/ /45.7/71 2.1/33.3/ /56/74 4.3/54/ /33.3/73.8 No Pakistan SouthAfrica India Cambodia Nepal Nigeria Ghana Uganda nd 2nd 1st 1st 1st 2nd 1st calculatedfromthenumberofdistributeddoses.thelattercalculationsalsoshowacomparablerangeacrossseveralcountries(figure1).giventhatgovernment offcialvaccinesurveillanceprogrammesroutinelyrelyonpassivereporting(26),therateofadrs fromhpvandothervaccinesmaybefurtherunder estimated. 1st everscreened 1.9(Allwomenaged18 69y 13.6(Allwomenaged18 69y screenedevery3y 2.6(Allwomenaged18 69y None 2.4(Allwomenaged18 69y screenedevery3y None 2.7(Allwomenaged18 69y None 6/59.3/ /58.4/62.8 6/56/ /33.3/72.6 6/59.3/ /41.3/50 4.6/41.3/50 6.7/37.9/74.1 No Accordingtosomeestimates,only1 10%oftheADRsintheUS arereportedtovaers(27). ThelackofdataonseriousADRsincountrieswhereroutine HPVvaccinationforyoungwomenisrecommendedandstrongly promoted(tableii)greatlyhampersourunderstandingaboutthe TableII.Summaryofadversereactions(ADRs)fromHPVvaccinesGardasilandCervarix.NotethattheUSFDACodeofFederalRegulationdefinesaserious adversedrugeventas anyadversedrugexperienceoccurringatanydosethatresultsinanyofthefollowingoutcomes:death,alife threateningadversedrug experience,inpatienthospitalizationorprolongationofexistinghospitalization,apersistentorsignificantdisability/incapacity,oracongenitalanomaly/birth defect (106). Vaccine Country Totaln ADRs(ref.) Dosesn(ref.) Gardasil US 18,727(7) 35,000,000 a (7) France 1,700(34) 4,000,000 a (34) Australia 1,534(39) 6,000,000 a (39) Ireland 314(33) 90,000 b (33) Cervarix Netherlands 575(32) 192,000 b (32) UK 8,798(23) 3,500,000 b (23) na= notavailable. a Dosesdistributed. b Dosesadministered. c Excluding2010data(unavailableatthetimeofwritingofthisreport). Total n ADRs/100,000 doses Total n serious ADRs(ref.) 1,498(7) na 91 c (26,28,29) na 575(32) na Total n serious ADRs/100,000doses c 5.7
4 4L. Tomljenovic & C. A. Shaw Figure 1. The rate of adverse reactions (ADRs) from Gardasil and Cervarix reported through various government official vaccine surveillance programmes. For the data source, see Table II. overallsafetyofthevarioushpvvaccinationprogrammes.nonetheless, analysis of the UK Medicines and Healthcare products RegulatoryAgency(MHRA)vaccinesafetydatashowsthatthere may be valid reasons for concern. For example, the total number of ADRs reported for Cervarix appears to be times higher than that reported for any of the other vaccines in the UKimmunizationschedule(Figure2). Off cial reports on adverse events following immunization (AEFI) in Australia also raise concerns(26). In 2008, Australia reported an annual AEFI rate of 7.3/100,000, the highest since 2003, representing an 85% increase compared with AEFI rate from2006(26).thisincreasewasalmostentirelyduetoaefis reportedfollowingthecommencementofthenationalhpvvaccinationprogrammeforfemalesaged12 26yearsinApril2007 (705 out of a total of 1538 AEFI records). Thus, nearly 50% of allaefisreportedduring2007wererelatedtothehpvvaccine. Moreover, HPV vaccine was the only suspected vaccine in 674 (96%) records, 203 (29%) had causality ratings of certain or probable,and43(6%)weredefinedas serious.themostsevere AEFIsreportedfollowingHPVvaccinationwereanaphylaxisand convulsions.notably,in2007,10outof13reportedanaphylaxis (77%) and 18 out of 35 convulsions (51%) occurred in women followinghpvvaccination(26).during2008,thehpvvaccine wasstillthenumberonevaccineonthelistofaefisinaustralia, with497records(32%ofallaefis),andaccountablefornearly 30%ofconvulsions(13outof43)(28).During2009,theAustralianreportedAEFIrateforadolescentsdecreasedbyalmost50% (from 10.4 to 5.6/100,000)(29). This decline in AEFI rates was attributedtoareductioninthenumbersofhpvvaccine related reports, following cessation of the catch up component of the HPV programme(29). Namely, the percentage of AEFIs related to HPV vaccines was only 6.4 in 2009 (29) compared to 50 in 2007(26).InspiteoftheoverallsignificantdecreaseinAEFIrate, the percentage of convulsions attributable to the HPV vaccine remainedcomparablebetween2007and2009(51%(26)and40% (29),respectively). Cumulatively,thelistofseriousADRsrelatedtoHPVvaccinationintheUS,UK,Australia,Netherlands,France,andIreland includes deaths, convulsions, syncope, paraesthesia, paralysis, Guillain Barrésyndrome(GBS),transversemyelitis,facialpalsy, chronic fatigue syndrome, anaphylaxis, autoimmune disorders, deep vein thrombosis, pulmonary embolisms, and pancreatitis (23,24,26,28 35). Itmaybethusappropriatetoaskwhetheritisworthrisking deathoradisablinglifelongneurodegenerativeconditionsuch asgbsatapreadolescentageforavaccinethathasonlyatheoreticalpotentialtopreventcervicalcancer,adiseasethatmaydevelop20 40yearsafterexposuretoHPV,when,asHarpernoted, thesamecanbepreventedwithregularpapscreening(36)? Itisalsoofnotethatinthepost licensureperiod( ), theusvaersreceived360reportsofabnormalpapsmears,112 reports of cervical cancer dysplasia, and 11 reports of cervical cancersrelatedtohpvvaccines(35).inareporttothefda(37), Merckexpressedtwo importantconcerns regardingadministration of Gardasil to girls with pre existing HPV 16/18 infection. One was the potential of Gardasil to enhance cervical disease, andtheother wastheobservationsofcin2/3orworsecasesdue tohpvtypesnotcontainedinthevaccine.accordingtomerck, ThesecasesofdiseaseduetootherHPVtypeshavethepotentialtocountertheeffcacyresultsofGardasilfortheHPVtypes containedinthevaccine. Table17inMerck sreporttothefda shows that Gardasil had an observed effcacy rate of 44.6% in subjectswhowerealreadyexposedto relevanthpvtypes (37). If,asimpliedbyMerck sownsubmission,gardasilmayexacerbate Figure 2. The rate of adverse reactions (ADRs) from Cervarix compared to that of other vaccines in the UK immunization schedule. Data sourced from the report provided by the UK Medicines and Healthcare products Regulatory Agency (MHRA) for the Joint Committee on Vaccination and Immunisation in June 2010 (23).
5 HPV vaccines and evidence-based medicine 5 the very disease it is supposed to prevent, why do the US FDA and the CDC allow for preadolescent girls and young women to be vaccinated with Gardasil without prescreening them for HPV 16/18infections? Side-effects from HPV vaccines: are they a minor concern? Accordingtogovernmentalhealthagenciesworldwide,including theuscdc,healthcanada,theaustraliantherapeuticgoods Administration(TGA),theUKMHRA,andtheIrishMedicines Board(IMB),thevastmajorityofadversereactionsfromeither GardasilorCervarixarenon serious(6,23,24,38,39).thesesourcesfurtherstatethatmostparticipantsreportbriefsorenessatthe injectionsite,headache,nausea,fever,andfainting(6,23,24,38,39). Moreover,theUKMHRAandtheUSFDAandtheCDCmaintain that fainting is common with vaccines (especially among adolescents)andhencenotareasonforconcern(6,23).specifically,theukmhrastatesthat Psychogenicevents including vasovagal syncope, faints and panic attacks can occur with any injectionprocedure andthat sucheventscanbeassociatedwith awiderangeoftemporarysignsandsymptomsincludinglossof consciousness, vision disturbances, injury, limb jerking (often misinterpreted as a seizure/convulsion), limb numbness or tingling,diffcultyinbreathing,hyperventilationetc. (23). TheVAERSdatashowthatsince2006whenitwasfirst approved,gardasilhasbeenassociatedwith18,727adversereactionsintheusalone,8%ofwhichwereserious(1498)including 68deaths(TableII).Areporttoanypassivevaccinesurveillance systemdoesnotbyitselfprovethatthevaccinecausedanadr. Systematic,prospective,controlledtrialsareneededtoestablish orrejectcausalrelationshipswithregardtodrug relatedadverse reactionsofanytype.nevertheless,theunusuallyhighfrequency ofreportsofadrsrelatedtohpvvaccines(figure2),aswellas theirconsistentpattern(i.e.withonlyminordeviations,nervous system relateddisordersrankthehighestinfrequencyacrossdifferentcountries,followedbygeneral/administrationsiteconditionsandgastrointestinaldisorders)(figure3),indicatesthatthe risksofhpvvaccinationmaynothavebeenfullyevaluatedin clinicaltrials.indeed,intheiranalysisofadrsofpotentialautoimmuneaetiologyinalargeintegratedsafetydatabaseofaso4 adjuvantedvaccines(anoveladjuvantsystemcomposedof3 Odesacyl 4 monophosphoryllipidaandaluminumsaltsusedin Cervarix),Verstraetenetal.(40)acknowledgethat Itisimportant tonotethatnoneofthesestudiesweresetupprimarilytostudy autoimmunedisorders. Ifthepurposeofthestudywasindeedto assessadrsof potentialautoimmuneaetiology,asthetitleitself clearlystates(40),thenthestudyshouldhavebeendesignedto detectthem.alloftheeightauthorsoftheaso4safetystudy areemployeesofglaxosmithkline(gsk),themanufacturerof Cervarix(40).Theseauthorsnotedthat oursearchoftheliteraturefoundnostudiesconductedbyindependentsourcesonthis subject and Allstudiesincludedinthisanalysiswerefundedby GSKBiologicals,aswastheanalysisitself.GSKBiologicalswas involvedinthestudydesign,datacollection,interpretationand analysis,preparationofthemanuscriptanddecisiontopublish (40). Giventhatvaccinescantriggerautoimmunedisorders(41 44), a more rigorous safety assessment than that provided by the GSK sponsoredstudywouldappeartohavebeenwarranted. Figure 3. Percentages of reported ADRs associated with HPV vaccines for each system organ class. Data sourced from the Database of the Netherlands Pharmacovigilance Centre Lareb (32), the UK Medicines and Healthcare products Regulatory Agency (MHRA) (62), and the Irish Medicines Board (IMB) (24). The most commonly reported ADRs in the nervous system and psychiatric disorders class were headache, syncope, convulsions, dizziness, hypoaesthesia, paraesthesia, lethargy, migraine, tremors, somnolence, loss of consciousness, dysarthria, epilepsy, sensory disturbances, facial palsy, grand mal convulsion, dysstasia, dyskinesia, hallucination, and insomnia.
6 6L. Tomljenovic & C. A. Shaw Meanwhile, independent scientific reports have linked HPV vaccination with serious ADRs, including death (45,46), amyotrophic lateral sclerosis (ALS) (45), acute disseminated encephalomyelitis (ADEM) (47 49), multiple sclerosis (MS) (50 52),opsoclonus myoclonussyndrome(oms)(whichischaracterized by ocular ataxia and myoclonic jerks of the extremities)(53), orthostatic hypotension (54), brachial neuritis (55), visionloss(56),pancreatitis(57),anaphylaxis(58),andpostural tachycardiasyndrome(pots)(59). ADEMandMSareseriousdemyelinatingdiseasesofthecentral nervoussystemthattypicallyfollowafebrileinfectionor vaccination(49,50,60).bothdisordersarealsothoughttobetriggeredby anautoimmunemechanism(50).clinicalsymptomsincluderapid onset encephalopathy, multifocal neurologic deficits, demyelinatinglesions,opticneuritis,seizures,spinalconditions,andvariable alterationsofconsciousnessormentalstatus(47,49,60).regarding POTS,thereportedcasehadnootherrelevantfactorsoreventsprecedingthesymptomsonsetapartfromGardasilvaccination(59). POTSisdefinedasthedevelopmentoforthostaticintolerance(61). According to Blitshteyn, It is probable that some patients who developpotsafterimmunizationwithgardasilorothervaccines are simply undiagnosed or misdiagnosed, which leads to underreporting and a paucity of data on the incidence of POTS after vaccinationinliterature (59).PatientswithPOTStypicallypresent withcomplaintsofdiminishedconcentration,tremulousness,dizzinessandrecurrentfainting,exerciseintolerance,fatigue,nausea andlossofappetite(59,61).suchsymptomsmaybeincorrectlylabelledaspanicdisordersorchronicanxiety.notably,symptomsof POTSappeartobeamongthemostfrequentADRsreportedafter vaccinationwithhpvvaccines(6,23,24,39).inspiteofthis,health authoritiesworldwidedonotregardtheseoutcomesascausallyrelatedtothevaccine(6),butratheras psychogenicevents (23,39). In summary, it appears that many medical authorities may have been too quick to dismiss a possible link between HPV vaccinesandseriousadrsbyrelyingheavilyondataprovided by the vaccine manufacturers rather than from independent research.theukmhrastatesthat Thevastmajorityofsuspected ADRs reported to MHRA in association with Cervarix vaccinecontinuetoberelatedtoeitherthesignsandsymptoms of recognized side effects listed in the product information or totheinjectionprocessandnotthevaccineitself(i.e. psychogenic innaturesuchasfaints) (23).Itisinterestingtonotethat theentiregroupofsystemclassdisordersshowninfigure3is regarded as unrelated to the HPV vaccine by the MHRA. AccordingtotheAgency, ThesesuspectedADRsarenotcurrently recognisedassideeffectsofcervarixvaccineandtheavailable evidencedoesnotsuggestacausallinkwiththevaccine.th ese are isolated medical events which may have been coincidental withvaccination (23,62).However,thefactthatasimilarpattern ofsystemclassadrstothatintheukhasalsobeenobservedin atleasttwoothercountriesarguesagainstthemhraconclusion andsuggeststheopposite,namelyacausalrelationshipwiththe HPVvaccine(Figure3). Safety assessment of HPV vaccines in clinical trials: was it adequate? Adouble blinded,placebo controlledtrialisconsideredthe gold standard forclinicaltrialsasitisthoughttopreventpotentialresearchers biasesfromdistortingtheconductofatrialand/orthe interpretationoftheresults(63).biases,however,maystilloccur due to selective publication of findings from within such trials, subject selection factors (inclusion/exclusion criteria), as well as placebochoices.withregardtothelatter,accordingtothefda,a placebois aninactivepill,liquid,orpowderthathasnotreatment value (63).Itisthereforesurprisingthustonotethatnoregulations governplacebocomposition,giventhatcertainplaceboscaninfluencetrialoutcomes(64).specifically,placebocompositioncan,in principle,bemanipulatedtoproduceresultsthatarefavourableto thedrugeitherintermsofsafetyoreffcacy(64). TheclinicaltrialsforGardasilandCervarixusedanaluminumcontaining placebo (15,20,40,65 69). Both HPV vaccines, like manyothervaccines,areadjuvantedwithaluminuminspiteof well documented evidence that aluminum can be highly neurotoxic (70 72). Moreover, current research strongly implicates aluminum adjuvants in various neurological and autoimmune disordersinbothhumansandanimals(41,73 80).Itisthusbecomingincreasinglyclearthattheroutineuseofaluminumasa placeboinvaccinetrialsisnotappropriate(80,81). Notably, safety data for Gardasil presented in Merck s packageinsertandthefdaproductapprovalinformation(82)show thatcomparedtothesalineplacebo,thosewomenreceivingthe aluminum containingplaceboreportedapproximately2 5times more injectionsite ADRs. On the other end, the proportion of injectionsiteadrsreportedinthegardasiltreatmentgroupwas comparabletothatofthealuminum control group(tableiii). Thus,Merck sowndataseemtoindicatethatalargeproportion ofadrsfromthehpvvaccinewereduetotheeffectofthealuminumadjuvant. For the assessment of serious conditions, the manufacturer pooledtheresultsfromthestudyparticipantswhoreceivedthe salineplacebowiththosewhoreceivedthealuminum containing placeboandpresentedthemasone control group.theoutcome ofthisprocedurewasthatgardasilandthealuminum control group had exactly the same rate of serious conditions (2.3%) (TableIV). Inarecentmeta analysisofsafetyandeffcacyofhpvvaccines, seventrialsenrollingatotalof44,142femaleswereevaluated(83). Twomainpopulationsofwomenweredefinedinthesetrials:those who received three doses of the HPV vaccine or the aluminumcontainingplacebowithinayear(denotedastheper protocolpopulation(ppp)),andthosewhoreceivedatleastoneinjectionofthe vaccine or the placebo within the same period (intention to treat population (ITT)). While HPV vaccine effcacy was evaluated in bothpppandittcohorts,vaccinesafetywasprimarilyevaluated intheittcohort(83).althoughittanalysisis conservative for assessment of treatment benefits (since dropouts may occur), it is anti conservative forassessmentofadrs,becauseadrswilloccur Table III. Injectionsite adverse reactions (ADRs) reported in Gardasil clinical trials among 8878 female participants aged 9 26 years, 1 5 days post vaccination(82). Aluminum(AAHS) a Salineplacebo ADRtype Gardasil(n =5088)% (n =3470)% (n =320)% Gardasil/saline Gardasil/AAHS AAHS/saline Pain Swelling Erythema Pruritus Bruising a AAHSControl= amorphousaluminumhydroxyphosphatesulfate.
7 HPV vaccines and evidence-based medicine 7 Table IV. Number of girls and women aged 9 26 years who reported a condition potentially indicative of a systemic autoimmune disorder after enrolmentingardasilclinicaltrials(82). Aluminum(AAHS) Gardasil(n =10,706) a (n =9412) Condition n(%) n(%) Arthralgia/arthritis/arthropathy 120(1.1) 98(1.0) Autoimmunethyroiditis 4(0.0) 1(0.0) Coeliacdisease 10(0.1) 6(0.1) Insulin dependent 2(0.0) 4(0.0) Diabetesmelitusinsulin dependent 2(0.0) 2(0.0) Erythemanodosum 27(0.3) 21(0.2) Hyperthyroidism 35(0.3) 38(0.4) Hypothyroidism 7(0.1) 10(0.1) Inflammatoryboweldisease 2(0.0) 4(0.0) Multiplesclerosis 2(0.0) 5(0.1) Nephritis 2(0.0) 0(0.0) Opticneuritis 4(0.0) 3(0.0) Pigmentationdisorder 13(0.1) 15(0.2) Psoriasis 3(0.0) 4(0.0) Raynaud sphenomenon 6(0.1) 2(0.0) Rheumatoidarthritis 2(0.0) 1(0.0) Scleroderma/morphea 1(0.0) 0(0.0) Stevens Johnsonsyndrome 1(0.0) 3(0.0) Sytemiclupuserythematosus 3(0.0) 1(0.0) Uveitis 3(0.0) 1(0.0) Total 245(2.3) 218(2.3) lessfrequentlyiffewerdosesofthevaccineareadministered.th us, suchaselectionproceduremayexplainwhythemeta analysisfound therisk to benefitratiotobeinfavourofthehpvvaccines(83). Theseventrialsincludedinthemeta analysiswereallsponsored bythevaccinemanufacturers(14,15,20,65 69).Inalengthyreport ofpotentialconflictsofinterestsofthefutureiitrialstudygroup (15),themajorityofauthorsdeclared receivinglecturefeesfrom Merck,SanofiPasteur,andMerckSharp&Dohme.Inaddition, IndianaUniversityandMerckhaveaconfidentialagreementthatpays theuniversityonthebasisofcertainlandmarksregardingthehpv vaccine. Inthe2009JAMAeditorial(11),Haugnotedthat When weighingevidenceaboutrisksandbenefits,itisalsoappropriateto askwhotakestherisk,andwhogetsthebenefit.patientsandthe publiclogicallyexpectthatonlymedicalandscientificevidenceis putonthebalance.ifothermattersweighin,suchasprofitfora companyorfinancialorprofessionalgainsforphysiciansorgroups ofphysicians,thebalanceiseasilyskewed.thebalancewillalsotilt iftheadverseeventsarenotcalculatedcorrectly. Are there safe and effective alternatives to HPV vaccination? Although approximately 275,000 women die annually from cervicalcancerworldwide,almost88%ofthesedeathsoccurin developing countries. Such disproportion of cancer deaths may besurprisinggiventhattheprevalenceofhpv 16/18inwomen withcervicalcancerisequalinbothdevelopinganddeveloped countries(71.0%and70.8%,respectively)(tablev).furthermore, HPV 16andHPV 18arethemostoncogenicofallHPVsubtypes and increasingly dominant with increasing severity of cervical cancerlesions(tablei)(84).nonetheless,analysisofwhodata in Figure 4 shows that HPV 16/18 prevalence in women with high gradelesionsaswellascervicalcancerisnotasignificant promoterofhighcervicalcancermortalityindevelopingcountries (P = ), but rather it is the lack of or insuffcient Papscreeningcoverage(P < ).Thesedatadonotdispute that HPV 16/18 infection is a primary prerequisite for cervical cancer.however,theydopointtootherco factorsasnecessary determinantsofbothdiseaseprogressionandoutcome(85). TheeffcacyofregularPapscreeningproceduresindeveloped countriesisfurtheremphasizedbythefactthatsuchprogrammes helped to achieve a 70% reduction in the incidence of cervical cancer over the last five decades (10,12,86,87). Conversely, in Finland,whenwomenstoppedattendingPapscreens,a4 foldincreaseincervicalcanceroccurredwithin5yearsfromscreening cessation(88,89). ItshouldbeemphasizedthatHPVvaccinationdoesnotmake Papscreeningobsolete,especiallysincethecurrentHPVvaccines guardonlyagainst2outof15oncogenichpvstrains.harpernotedthatifhpv vaccinatedwomenstoppedgoingforpapsmears, the incidence rate of cervical cancer would increase (36,86). A similarconcernwasalsoraisedbyfrenchandcanadianresearcherswhosuggestedthepossibilitythatvaccinatedwomenmightbe lessinclinedtoparticipateinscreeningprogrammes(87,90).such outcomeswouldinturncompromisetimelyspecialistreferralof casesharbouringprecancerouslesions,especiallythoserelatedto HPVgenotypesotherthan16/18(90). Are HPV vaccines cost-effective? Th ecurrentlylicensedhpvvaccinesareamongthemostexpensivevaccinesonthemarket(i.e.gardasilcurrentlycostsus$400 forthethreerequireddoses)(87),makingitunlikelythatthose countries with the heaviest burden of cervical cancer mortality (i.e.uganda,nigeria,andghana)wouldeverbenefit from them.thatisundertheassumptionthatthelong termbenefits fromhpvvaccination(i.e.cancerprevention)wereproven.for example, preadolescent HPV vaccination in Thailand is costeffectiveonlywhenassuminglifelongeffcacyandacostof10 international dollars (I$, a currency that provides a means of translatingandcomparingcostsamongcountries)pervaccinated girl(approximatelyi$2/dose)orless(91).thecost effectiveness analysisofhpvvaccinationforeasternafricashowsasimilar outcome(25).incountrieswherepricingislessofanissue,such astheus,hpvvaccinationisonlycost effectivebasedonthe assumption of complete and lifelong vaccine effcacy and 75% coverageofthetargetedpreadolescentpopulation(92,93).inthe Netherlands,HPVvaccinationisnotcost effectiveundersimilar assumptions(e.g.thatthehpvvaccineprovideslifelongprotectionagainst70%ofallcervicalcancers,hasnoside effects,and isadministeredtoallwomenregardlessoftheirriskofcervical cancer)(94).notethatthereasonwhyhighcoverageisneeded for a vaccine to be cost effective in the developed countrysetting is the very low incidence of cervical cancer (due to effectivenessofpapscreeningprogrammes).forexample,toprevent asingleoutof5.7/100,000cervicalcancercases(oroneoutof 1.7/100,000cervicalcancerdeaths)intheUS,nearlyeverygirl wouldneedtobevaccinatedforthehpvvaccineprogrammeto becost effective. The increased pressure to make the HPV vaccines mandatory for all preadolescent girls makes the cost of the HPV vaccinationprogrammeasignificantissue.forexample,according toa2006reportinthe New York Times (95),tomakeGardasil mandatorywouldprobablydoublethecostoftheusvaccination programme: North Carolina, for instance, spends $11 million annuallytoprovideeverychildwithsevenvaccines.gardasilalone wouldprobablycostatleastanother$10million. UndertheassumptionthattheHPVvaccineoffersfullprotectionagainstHPV infectionfor5years,an11 year oldgirlwouldneed13booster shotsifsheweretolivetotheageof75.atacurrentcostofus $120perdose,thetotalcostforvaccinatingonegirlwouldthus exceedus$1500.accordingtosomeestimates,tovaccinateevery 11 and12 year oldgirlintheuswouldcostus$1.5billionandto
GLOBAL CONCERNS ABOUT HPV VACCINES FACT SHEET
GLOBAL CONCERNS ABOUT HPV VACCINES FACT SHEET When detected, HPV infection is easily managed and rarely proceeds to cancer Very few women with HPV develop cervical cancer HPV infections are only one of
More informationHuman Papillomavirus (HPV) Vaccines as an Option for Preventing Cervical Malignancies: (How) Effective and Safe?
Send Orders of Reprints at reprints@benthamscience.org Current Pharmaceutical Design, 2013, 19, 000-000 1 Human Papillomavirus (HPV) Vaccines as an Option for Preventing Cervical Malignancies: (How) Effective
More informationSafety of HPV vaccination: A FIGO STATEMENT
Safety of HPV vaccination: A FIGO STATEMENT July, 2013 Human papillomavirus vaccines are used in many countries; globally, more than 175 million doses have been distributed. Extensive pre- and post-licensure
More informationMedia Contacts: Annick Robinson Investor Contacts: Justin Holko (438) 837-2550 (908) 740-1879 annick.robinson@merck.com
News Release FOR IMMEDIATE RELEASE Media Contacts: Annick Robinson Investor Contacts: Justin Holko (438) 837-2550 (908) 740-1879 annick.robinson@merck.com Merck's HPV Vaccine, GARDASIL 9, now available
More informationHow To Get An Hp Vaccine
What is HPV? HPV Vaccines HPV is short for human papilloma virus. HPVs are a group of more than 150 related viruses. Each HPV virus in the group is given a number, which is called an HPV type. HPVs are
More informationOREGON HEALTH AUTHORITY IMMUNIZATION PROTOCOL FOR PHARMACISTS Human Papilloma Virus Vaccines (HPV)
OREGON HEALTH AUTHORITY IMMUNIZATION PROTOCOL FOR PHARMACISTS Human Papilloma Virus Vaccines (HPV) Revisions as of 01-01-2016 Vaccination age changed to clients 7 years of age Removal of adolescent well
More informationSummary of Key Points WHO Position Paper on Vaccines against Human Papillomavirus (HPV) October 2014
Summary of Key Points WHO Position Paper on Vaccines against Human Papillomavirus (HPV) October 2014 1 Background l Selected types of HPV cause cervical cancer, anogenital warts, and other anogenital and
More information4/30/2013 HPV VACCINE AND NORTH DAKOTA HPV IMMUNIZATION RATES HUMAN PAPILLOMAVIRUS (HPV) HUMAN PAPILLOMAVIRUS HPV CONTINUED
HPV VACCINE AND NORTH DAKOTA HPV IMMUNIZATION RATES HUMAN PAPILLOMAVIRUS (HPV) HUMAN PAPILLOMAVIRUS What is human papillomavirus (HPV)? HPV is the most common sexually transmitted infection. There are
More informationRecommendations for Human Papillomavirus (HPV) Vaccine Schedule. Provincial Infectious Diseases Advisory Committee (PIDAC)
Recommendations for Human Papillomavirus (HPV) Vaccine Schedule Provincial Infectious Diseases Advisory Committee (PIDAC) 2015 Public Health Ontario Public Health Ontario is a Crown corporation dedicated
More informationFive Key Steps to Improve HPV Vaccination Rates in Your Practice. Tuesday, December 9, 2014 11:00 AM ET
Five Key Steps to Improve HPV Vaccination Rates in Your Practice Tuesday, December 9, 2014 11:00 AM ET Agenda Welcome & Program Goals Accelerating HPV Vaccine Uptake: A Public Health Priority Joseph A.
More informationWilliam Atkinson, MD, MPH Hepatitis B Vaccine Issues June 16, 2016
William Atkinson, MD, MPH Hepatitis B Vaccine Issues June 16, 2016 Advisory Committee on Immunization Practices (ACIP) The recommendations to be discussed are primarily those of the ACIP composed of 15
More informationAmerican Academy of Family Physicians
American Academy of Family Physicians Barbara E. Stanford MD Grand Rapids Family Medicine Residency Wege Family Medicine HPV is transient in most women HPV-75% Normal ASCUS LSIL HSIL Cancer 80-90% 75%???
More informationTen Good Reasons to Be Concerned about the Human Papillomavirus (HPV) Vaccination Campaign
Ten Good Reasons to Be Concerned about the Human Papillomavirus (HPV) Vaccination Campaign This document is a translation and adaption of an information brochure prepared by the Federation du Québec pour
More informationImmunization Healthcare Branch. Human Papillomavirus Vaccination Program Questions and Answers. Prepared by
Immunization Healthcare Branch Human Papillomavirus Vaccination Program Questions and Answers Prepared by Immunization Healthcare Branch (IHB), Defense Health Agency Last Updated: 02 Jan 14 www.vaccines.mil
More informationThe pathogenesis of human Papillomavirus (HPV) in the development of cervical cancer: are HPV vaccines a safe and effective management strategy?
University of Wollongong Research Online Faculty of Law, Humanities and the Arts - Papers Faculty of Law, Humanities and the Arts 2011 The pathogenesis of human Papillomavirus (HPV) in the development
More informationCervical Screening and HPV Vaccine Guidelines In Saudi Arabia. Prof. Mohammed Addar Chairmen Gyneoncology section KKUH, King Saud University
Cervical Screening and HPV Vaccine Guidelines In Saudi Arabia Prof. Mohammed Addar Chairmen Gyneoncology section KKUH, King Saud University Burden of HPV related cancers l l Cervical Cancer of the cervix
More informationFrequently Asked Questions (FAQs)
Frequently Asked Questions (FAQs) Research Rationale 1. What does PrEP stand for? There is scientific evidence that antiretroviral (anti-hiv) medications may be able to play an important role in reducing
More informationImmunization Safety Office. Updates
Immunization Safety Office Updates Centers for Disease Control and Prevention Tom Shimabukuro, MD, MPH, MBA Immunization Safety Office Division of Healthcare Quality Promotion National Center for Emerging
More informationMHRA PUBLIC ASSESSMENT REPORT
MHRA PUBLIC ASSESSMENT REPORT Cervarix (HPV vaccine): Update on UK safety covering the first two years of the HPV immunisation programme October 2010 Plain language summary 2 1. Introduction 4 2. Background
More informationVaccination against pertussis (whooping cough) - the replacement of Repevax with Boostrix -IPV an update for registered healthcare practitioners
Vaccination against pertussis (whooping cough) - the replacement of Repevax with Boostrix -IPV an update for registered healthcare practitioners Questions and Answers May 2014 Health Protection Scotland
More informationIntroduction to Post marketing Drug Safety Surveillance: Pharmacovigilance in FDA/CDER
Introduction to Post marketing Drug Safety Surveillance: Pharmacovigilance in FDA/CDER LT Andrew Fine, Pharm.D., BCPS Safety Evaluator Division of Pharmacovigilance Office of Pharmacovigilance and Epidemiology
More informationFacts About Chickenpox and Shingles for Adults
Facts About Chickenpox and Shingles for Adults What is chickenpox? Chickenpox, also known as varicella, is a very contagious disease caused by the varicella-zoster virus. It is spread easily through the
More informationInfluenza Vaccine Frequently Asked Questions. Influenza Control Program
Influenza Vaccine Frequently Asked Questions Influenza Control Program Influenza or the flu can be a serious contagious disease, which is spread by droplet transmission through close contact with an infected
More informationAn Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI)
An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI) Update on the recommended Human Papillomavirus (HPV) vaccine immunization schedule TO PROMOTE AND PROTECT THE HEALTH
More informationHPV Vaccines. What is HPV? Can a vaccine help prevent HPV?
What is HPV? HPV Vaccines HPV stands for human papilloma virus. HPVs are a group of more than 150 related viruses. Each HPV virus in the group is given a number, and is called an HPV type (for instance,
More informationAnaphylaxis and other adverse events
Anaphylaxis and other adverse events Aim: To be able to manage anaphylaxis and other adverse events correctly Learning outcomes Define local and systemic adverse events Distinguish between anaphylaxis
More informationExamples of good screening tests include: mammography for breast cancer screening and Pap smears for cervical cancer screening.
CANCER SCREENING Dr. Tracy Sexton (updated July 2010) What is screening? Screening is the identification of asymptomatic disease or risk factors by history taking, physical examination, laboratory tests
More informationCXCA-MSP. The next step in cervical cancer prevention! GynTect : Epigenetic biomarkers for reliable cancer diagnostics. www.gbo.
CXCA-MSP The next step in cervical cancer prevention! GynTect : Epigenetic biomarkers for reliable cancer diagnostics www.gbo.com/diagnostics H 3 C NH 2 NH H 3 C 2 N mc N mc N H N O H O The challenge of
More informationTwo-Year Phase III Data Presented at AAN 61st Annual Meeting Show Positive Outcome of Cladribine Tablets in Patients with Multiple Sclerosis
Your contact News Release Barbara Fry Phone +1 905 919 0163 April 29/30, 2009 Two-Year Phase III Data Presented at AAN 61st Annual Meeting Show Positive Outcome of Cladribine Tablets in Patients with Multiple
More informationClinical Commissioning Policy: Disease Modifying Therapies For patients With Multiple Sclerosis (MS) December 2012. Reference : NHSCB/D4/c/1
Clinical Commissioning Policy: Disease Modifying Therapies For patients With Multiple Sclerosis (MS) December 2012 Reference : NHSCB/D4/c/1 NHS Commissioning Board Clinical Commissioning Policy: Disease
More informationEMA and Progressive Multifocal Leukoencephalopathy.
EMA and Progressive Multifocal Leukoencephalopathy. ENCePP Plenary, London 23 November 2011 Presented by: Henry Fitt Head of Coordination & Networking, Pharmacovigilance & Risk Management An agency of
More informationCervical Cancer The Importance of Cervical Screening and Vaccination
Cervical Cancer The Importance of Cervical Screening and Vaccination Cancer Cells Cancer begins in cells, the building blocks that make up tissues. Tissues make up the organs of the body. Sometimes, this
More informationAdoption of N.J.A.C. 8:57-4 (Immunization of Pupils In School) with Amendments and New Rules
JON S. CORZINE Governor DEPARTMENT OF HEALTH AND SENIOR SERVICES PO BOX 360 TRENTON, N.J. 08625-0360 www.nj.gov/health FRED M. JACOBS, M.D., J.D. Commissioner TO: FROM: SUBJECT: Herbert Yardley, M.A. Chair
More informationGuidance on adverse drug reactions
Guidance on adverse drug reactions Classification of adverse drug reactions Adverse drug reactions are frequently classified as type A and type B reactions. An extended version of this classification system
More informationGroup Benefits Evidence of Insurability for Comprehensive Optional Critical Illness Insurance
Group Benefits Evidence of Insurability for Comprehensive Optional Critical Illness Insurance INSTRUCTIONS - Please print all answers If required, retain a photocopy for your files. 1a) Plan contract number(s)
More informationNew and Emerging Immunotherapies for Multiple Sclerosis: Oral Agents
New and Emerging Immunotherapies for Multiple Sclerosis: Oral Agents William Tyor, M.D. Chief, Neurology Atlanta VA Medical Center Professor, Department of Neurology Emory University School of Medicine
More informationInsurance. Chapter 7. Introduction
65 Chapter 7 Insurance Introduction 7.1 The subject of genetic screening in relation to insurance is not new. In 1935 R A Fisher addressed the International Congress of Life Assurance Medicine on the topic,
More informationClinical trials in haemophilia
Clinical trials in haemophilia Dr. Paul Giangrande Oxford Haemophilia and Thrombosis Centre & Nuffield Department of Clinical Medicine University of Oxford paul.giangrande@ndm.ox.ac.uk Why do clinical
More informationNATIONAL VACCINE INJURY COMPENSATION PROGRAM
NATIONAL VACCINE INJURY COMPENSATION PROGRAM Lawrence D. Frenkel, MD, FAAP, FACAAI, FPIDS Professor, Departments of Pediatrics and Microbiology University of Illinois College of Medicine Member, Division
More informationBACKGROUND MEDIA INFORMATION Fast facts about liver disease
BACKGROUND MEDIA INFORMATION Fast facts about liver disease Liver, or hepatic, disease comprises a wide range of complex conditions that affect the liver. Liver diseases are extremely costly in terms of
More informationHuman Papilloma Virus and HPV vaccine knowledge among Mustafa Kemal University Medical Students
Acta Medica Anatolia Volume 2 Issue 2 2014 Human Papilloma Virus and HPV vaccine knowledge among Mustafa Kemal University Medical Students Raziye Keskin Kurt 1, Atilla Karateke 1, Mehmet Erdem 2, Dilek
More informationDr. Valerie Jaeger Acting President Providing Leadership in Public Health Management
2 Carlton Street, Suite 1306 Toronto, Ontario M5B 1J3 Tel: (416) 595-0006 Fax: (416) 595-0030 E-mail: info@alphaweb.org alpha s members are the public health units in Ontario. alpha Sections: Boards of
More informationDisclosures. Consultant and Speaker for Biogen Idec, TEVA Neuroscience, EMD Serrono, Mallinckrodt, Novartis, Genzyme, Accorda Therapeutics
Mitzi Joi Williams, MD Neurologist MS Center of Atlanta, Atlanta, GA Disclosures Consultant and Speaker for Biogen Idec, TEVA Neuroscience, EMD Serrono, Mallinckrodt, Novartis, Genzyme, Accorda Therapeutics
More informationAutoimmune Diseases More common than you think Randall Stevens, MD
Autoimmune Diseases More common than you think Randall Stevens, MD picture placeholder Autoimmune Diseases More than 60 different disorders Autoimmune disorders (AID) diseases caused by the immune system
More informationVersion History. Previous Versions. Policy Title. Drugs for MS.Drug facts box Glatiramer Acetate Version 1.0 Author
Version History Policy Title Drugs for MS.Drug facts box Glatiramer Acetate Version 1.0 Author West Midlands Commissioning Support Unit Publication Date Jan 2013 Review Date Supersedes/New (Further fields
More informationCervical cancer is the second most common cancer among South African women
Cervical cancer is the second most common cancer among South African women *SA Statistics as per National Cancer Registry (NCR) 2007 What is cervical cancer? Cervical cancer is a type of cancer that occurs
More informationPertussis vaccine in both children and adults. Gaston De Serres. MD, PhD Institut national de santé publique du Québec, and Université Laval, Quebec
Pertussis vaccine in both children and adults Gaston De Serres. MD, PhD Institut national de santé publique du Québec, and Université Laval, Quebec Disclosure I received research grants from GSK (hepatitis
More informationEPIDEMIOLOGY OF HEPATITIS B IN IRELAND
EPIDEMIOLOGY OF HEPATITIS B IN IRELAND Table of Contents Acknowledgements 3 Summary 4 Introduction 5 Case Definitions 6 Materials and Methods 7 Results 8 Discussion 11 References 12 Epidemiology of Hepatitis
More informationVaccinating Every Adolescent Patient. Adjunct Professor of Family Medicine University of Minnesota at Mankato
Vaccinating Every Adolescent Patient Vince LaPorte LaPorte, MD Adjunct Professor of Family Medicine University of Minnesota at Mankato Funded by the Centers for Disease Control and Prevention via the Prevention
More informationCervical Cancer Screening and Management Guidelines: Changing Again, Huh?
Cervical Cancer Screening and Management Guidelines: Changing Again, Huh? Summary of 2013 recommendations from ASC (American Cancer Society), ASCCP (American Society for Colposcopy and Cervical Pathology),
More informationTdap booster vaccine for Health Care Workers Frequently Asked Questions for Health Professionals
Tdap booster vaccine for Health Care Workers Frequently Asked Questions for Health Professionals NEW items in 2013 Immunisation Guidelines for Ireland are in RED What is Tdap booster vaccine? Tdap is a
More informationCHPN Review Course Pain Management Part 1 Hospice and Palliative Nurses Association
CHPN Review Course Pain Management Part 1 Disclosures Bonnie Morgan has no real or perceived conflicts of interest that relate to this presentation. Copyright 2015 by the. HPNA has the exclusive rights
More informationPreventing Cervical Cancer with Gardasil Jana Ogden RN, MSN, MBA-HCA, IHCC Nursing Faculty. Upon Completion of the Lesson the student will be able to:
Preventing Cervical Cancer with Gardasil Jana Ogden RN, MSN, MBA-HCA, IHCC Nursing Faculty Upon Completion of the Lesson the student will be able to: Review statistics related to cervical cancer and HPV
More informationThe link between cervical cancer and HPV (human papillomavirus)
The link between cervical cancer and HPV (human papillomavirus) The link between cervical cancer and HPV Key facts: HPV is a virus (the human papillomavirus). Almost all abnormal Pap smear results are
More informationWhat is Multiple Sclerosis? Gener al information
What is Multiple Sclerosis? Gener al information Kim, diagnosed in 1986 What is MS? Multiple sclerosis (or MS) is a chronic, often disabling disease that attacks the central nervous system (brain and spinal
More informationAdverse Events Following Immunisation (AEFI) Noel McCarthy Thames Valley Public Health England Centre and Everybody
Adverse Events Following Immunisation (AEFI) Noel McCarthy Thames Valley Public Health England Centre and Everybody A fifteen year old with diabetes came for his MMR and was referred by the school nurse
More informationThe Minnesota Chlamydia Strategy: Action Plan to Reduce and Prevent Chlamydia in Minnesota Minnesota Chlamydia Partnership, April 2011
The Minnesota Chlamydia Strategy: Action Plan to Reduce and Prevent Chlamydia in Minnesota Minnesota Chlamydia Partnership, April 2011 Section 5: Screening, Treating and Reporting Chlamydia While the information
More informationIssues Regarding Use of Placebo in MS Drug Trials. Peter Scott Chin, MD Novartis Pharmaceuticals Corporation
Issues Regarding Use of Placebo in MS Drug Trials Peter Scott Chin, MD Novartis Pharmaceuticals Corporation Context of the Guidance The draft EMA Guidance mentions placebo as a comparator for superiority
More informationThings You Should Know About Adverse Event Report Data
U.S. Department of Health and Human Services Food and Drug Administration Center for Food Safety and Applied Nutrition CFSAN Adverse Event Reporting System Voluntary Reports on Red Bull Energy Drink January
More informationXI International Workshop of Lower Genital Tract Pathology HPV Disease: The global battle Rome 19-21 April 2012
XI International Workshop of Lower Genital Tract Pathology HPV Disease: The global battle Rome 19-21 April 2012 Thursday 19 nd April 2012 Morning Sessions 07.50-08.20 Registration 08.20-08.40 Welcome:
More informationacquired chronic immune-mediated inflammatory condition of CNS. MS in children: 10% +secondary progressive MS: rare +primary progressive MS: rare
Immunomodulatory Therapies in Pediatric MS Vuong Chinh Quyen Neurology Department Medscape Mar 8, 2013 Multiple Sclerosis in Children. Iran J Child Neurol. 2013 Spring Introduction acquired chronic immune-mediated
More informationOHTAC Recommendation
OHTAC Recommendation Multiple Sclerosis and Chronic Cerebrospinal Venous Insufficiency Presented to the Ontario Health Technology Advisory Committee in May 2010 May 2010 Issue Background A review on the
More informationScreening for Cancer in Light of New Guidelines and Controversies. Christopher Celio, MD St. Jude Heritage Medical Group
Screening for Cancer in Light of New Guidelines and Controversies Christopher Celio, MD St. Jude Heritage Medical Group Screening Tests The 2 major objectives of a good screening program are: (1) detection
More informationProspects for Vaccines against Hepatitis C Viruses. T. Jake Liang. M.D. Liver Diseases Branch NIDDK, NIH, HHS
Prospects for Vaccines against Hepatitis C Viruses T. Jake Liang. M.D. Liver Diseases Branch NIDDK, NIH, HHS HCV Vaccine Prevention strategies Protective immunity Barriers and solutions Vaccine candidates
More informationThe Burden of the Complicated Type 2 Diabetes Patient in China. White Paper
White Paper Catalysts driving successful decisions in life sciences. The Burden of the Complicated Type 2 Diabetes Patient in China by Marco DiBonaventura, Ph.D. Director, Health Economics and Outcomes
More informationThe largest clinical study of Bayer's Xarelto (rivaroxaban) Wednesday, 14 November 2012 07:38
Bayer HealthCare has announced the initiation of the COMPASS study, the largest clinical study of its oral anticoagulant Xarelto (rivaroxaban) to date, investigating the prevention of major adverse cardiac
More informationUpdated Recommendations for Use of Tdap in Pregnant Women
From the Texas Department of State Health Services Immunization Branch The goal of the Vaccine Advisory is to disseminate, in a timely manner, practical information related to vaccines, vaccine-preventable
More informationFAST TRACK DEVELOPMENT OF EBOLA VACCINES: FDA REGULATORY PERSPECTIVE
FAST TRACK DEVELOPMENT OF EBOLA VACCINES: FDA REGULATORY PERSPECTIVE Marion Gruber, Ph.D. Director Office of Vaccines Research & Review Center for Biologics Evaluation and Research US Food and Drug Administration
More informationCERVICAL CANCER What every woman should know What is a cervix?
CERVICAL CANCER What every woman should know What is a cervix? The cervix is the entrance to the womb from the vagina. It is the narrow, lower part of the uterus that is the passageway connecting the uterus
More informationImmunisation Services - Authority for Registered Nurses and Midwives
Policy Directive Ministry of Health, NSW 73 Miller Street North Sydney NSW 2060 Locked Mail Bag 961 North Sydney NSW 2059 Telephone (02) 9391 9000 Fax (02) 9391 9101 http://www.health.nsw.gov.au/policies/
More informationCervical cancer screening with the HPV test and the Pap test in women ages 30 and older
Cervical cancer screening with the HPV test and the Pap test in women ages 30 and older When to get tested and how to make sense of your test results If you are 30 years or older and your Pap test is normal
More informationThe Consequences of Missing Data in the ATLAS ACS 2-TIMI 51 Trial
The Consequences of Missing Data in the ATLAS ACS 2-TIMI 51 Trial In this white paper, we will explore the consequences of missing data in the ATLAS ACS 2-TIMI 51 Trial and consider if an alternative approach
More informationMULTIPLE SCLEROSIS AUSTRALIA MULTIPLE SCLEROSIS RESEARCH AUSTRALIA
MULTIPLE SCLEROSIS AUSTRALIA MULTIPLE SCLEROSIS RESEARCH AUSTRALIA Submission to the ACT Legislative Assembly Health, Ageing, Community and Social Services Inquiry into the exposure draft of the Drugs
More informationClinical Policy Title: Home uterine activity monitoring
Clinical Policy Title: Home uterine activity monitoring Clinical Policy Number: 12.01.01 Effective Date: August 19, 2015 Initial Review Date: July 17, 2013 Most Recent Review Date: July 15, 2015 Next Review
More informationHPV Clinical Research and Vaccines. Rachel Winer, PhD, MPH Department of Epidemiology University of Washington rlw@u.washington.
HPV Clinical Research and Vaccines Rachel Winer, PhD, MPH Department of Epidemiology University of Washington rlw@u.washington.edu Epidemiology of HPV The most common STD in the US and worldwide 80% sexually
More informationNP/PA Clinical Hepatology Fellowship Summary of Year-Long Curriculum
OVERVIEW OF THE FELLOWSHIP The goal of the AASLD NP/PA Fellowship is to provide a 1-year postgraduate hepatology training program for nurse practitioners and physician assistants in a clinical outpatient
More informationVaccines against human papillomavirus in low and middle income countries: a review of safety, immunogenicity and efficacy
Nakalembe et al. Infectious Agents and Cancer (2015) 10:17 DOI 10.1186/s13027-015-0012-2 REVIEW Vaccines against human papillomavirus in low and middle income countries: a review of safety, immunogenicity
More informationShutterstock TACstock
Shutterstock TACstock 10 Introduction Since 2000, the IDF Diabetes Atlas has detailed the extent of diabetes and this seventh edition shows how it is impacting every country, every age group and every
More informationPhysical Exam Checklist
1021 West 14 th Street P. O. Box 968 Hastings, Nebraska 68902-0968 Appointments (402) 463-2423 Business (402) 462-8456 Fax (402) 463-9698 Physical Exam Checklist This information is being sent to you for
More informationGUIDELINE DOCUMENT CERVICAL CANCER SCREENING IN SOUTH AFRICA 2015
GUIDELINE DOCUMENT CERVICAL CANCER SCREENING IN SOUTH AFRICA 2015 Cervical cancer remains an important cause of morbidity and mortality in South Africa. At present the national cervical cancer prevention
More informationNo. prev. doc.: 8770/08 SAN 64 Subject: EMPLOYMENT, SOCIAL POLICY, HEALTH AND CONSUMER AFFAIRS COUNCIL MEETING ON 9 AND 10 JUNE 2008
COUNCIL OF THE EUROPEAN UNION Brussels, 22 May 2008 9636/08 SAN 87 NOTE from: Committee of Permanent Representatives (Part 1) to: Council No. prev. doc.: 8770/08 SAN 64 Subject: EMPLOYMENT, SOCIAL POLICY,
More informationFactsheet September 2012. Pertussis immunisation for pregnant women. Introduction
Factsheet September 2012 Pertussis immunisation for pregnant women Introduction The routine childhood immunisation programme has been very effective in reducing the overall numbers of cases of pertussis.
More informationNatalizumab (Tysabri)
Natalizumab (Tysabri) Spirella Building, Letchworth, SG6 4ET 01462 476700 www.mstrust.org.uk reg charity no. 1088353 Natalizumab (Tysabri) Date of issue: July 2010 Review date: July 2011 Contents Section
More informationGuidance for Industry Diabetes Mellitus Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes
Guidance for Industry Diabetes Mellitus Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes U.S. Department of Health and Human Services Food and Drug Administration Center
More informationWORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI Ethical Principles for Medical Research Involving Human Subjects
WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI Ethical Principles for Medical Research Involving Human Subjects Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by
More informationBiogen Global Medical Grants Office Multiple Sclerosis: Areas of Interest
Biogen Global Medical Grants Office Multiple Sclerosis: Areas of Interest Cycle C June 2, 2015 1 Introduction The landscape for the treatment of relapsing Multiple Sclerosis (MS) has quickly evolved over
More informationBasic research methods. Basic research methods. Question: BRM.2. Question: BRM.1
BRM.1 The proportion of individuals with a particular disease who die from that condition is called... BRM.2 This study design examines factors that may contribute to a condition by comparing subjects
More informationAre Booster Doses of Hepatitis B Vaccine Necessary?
Are Booster Doses of Hepatitis B Vaccine Necessary? Current CDC Recommendations And Gaps in Knowledge Division of Viral Hepatitis Centers for Disease Control and Prevention, USA Current United States Recommendations
More informationA Guide to Clinical Trials
A Guide to Clinical Trials For young people with cancer and their parents Children s Cancer and Leukaemia Group www.cclg.org.uk Original booklet produced in conjunction with the CCLG Patient Advocacy Committee.
More informationBiomedical Engineering for Global Health. Lecture Thirteen
Biomedical Engineering for Global Health Lecture Thirteen Outline The burden of cancer How does cancer develop? Why is early detection so important? Strategies for early detection Example cancers/technologies
More informationUp to $402,000. Insight HIV. Drug Class. 1.2 million people in the United States were living with HIV at the end of 2011 (most recent data).
HIV Background, new developments, key strategies Drug Class Insight INTRODUCTION Human Immunodeficiency Virus (HIV) is the virus that can lead to Acquired Immunodeficiency Syndrome, or AIDS. No safe and
More informationHuman papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update
Int. J. Cancer: 121, 621 632 (2007) ' 2007 Wiley-Liss, Inc. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update Jennifer S. Smith
More informationNew York State Department of Health Immunization Program Combined Hepatitis A and B Vaccine Dosing Schedule Policy
New York State Department of Health Immunization Program Combined Hepatitis A and B Vaccine Dosing Schedule Policy Policy Statement The accelerated four-dose schedule for combined hepatitis A and B vaccine
More informationTHE REGIONAL MUNICIPALITY OF PEEL REGIONAL COUNCIL A D D I T I O N A L A G E N D A. February 12, 2015
THE REGIONAL MUNICIPALITY OF PEEL REGIONAL COUNCIL A D D I T I O N A L A G E N D A February 12, 2015 7. ITEMS RELATED TO ENTERPRISE PROGRAMS AND SERVICES Chaired by Councillor C. Fonseca or Vice-Chair
More informationThe submission positioned dimethyl fumarate as a first-line treatment option.
Product: Dimethyl Fumarate, capsules, 120 mg and 240 mg, Tecfidera Sponsor: Biogen Idec Australia Pty Ltd Date of PBAC Consideration: July 2013 1. Purpose of Application The major submission sought an
More informationHow To Get Immunizations At Clemson
Immunization Forms Welcome to Clemson University! We are glad you have chosen us to meet your higher education goals. The University requires a complete immunization record to be on file at for all students.
More informationXARELTO (rivaroxaban tablets) in Knee and Hip Replacement Surgery
XARELTO (rivaroxaban tablets) in Knee and Hip Replacement Surgery Fast Facts: XARELTO is a novel, once-daily, oral anticoagulant recently approved in the United States for the prevention (prophylaxis)
More informationEthics and Scientific Oversight for Phase 1 Clinical Trials in Hong Kong. Sydney TANG Chairman, HKU/HA HKW IRB November 21, 2015
Ethics and Scientific Oversight for Phase 1 Clinical Trials in Hong Kong Sydney TANG Chairman, HKU/HA HKW IRB November 21, 2015 Clinical Trials at HKU Phase 1 Phase II Phase III Phase IV Conducted on patient
More informationAPIC Practice Guidance Committee: Implementation Insights Prevention & Control of Pertussis
1275 K Street, NW, Suite 1000 Washington, DC 20005-4006 Phone: 202/789-1890 Fax: 202/789-1899 apicinfo@apic.org www.apic.org APIC Practice Guidance Committee: Implementation Insights Prevention & Control
More informationPrevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (AF) with one or more risk factors
News Release For use outside the US and UK only Bayer Pharma AG 13342 Berlin Germany Tel. +49 30 468-1111 www.bayerpharma.com Bayer s Xarelto Approved in the EU for the Prevention of Stroke in Patients
More information