Issues in assessing products for the treatment of hemophilia – the intersection between efficacy, economics, and ethics

References

• OlivieriMKurnikKPflugerTBidlingmaierCIdentification and long-term observation of early joint damage by magnetic resonance imaging in clinically asymptomatic joints in patients with haemophilia A or B despite prophylaxisHaemophilia201218336937422032268
   PubMed Web of Science ®Google Scholar
• Den UijlIFischerKVan Der BomJGGrobbeeDERosendaalFRPlugIAnalysis of low frequency bleeding data: the association of joint bleeds according to baseline FVIII activity levelsHaemophilia2011171414420825504
   PubMed Web of Science ®Google Scholar
• RogersGLHerzogRWGene therapy for hemophiliaFront Biosci (Landmark Ed)20152055660325553466
   PubMed Web of Science ®Google Scholar
• SpencerHTDenningGGautneyRELentiviral vector platform for production of bioengineered recombinant coagulation factor VIIIMol Ther201119230230921081907
   PubMed Web of Science ®Google Scholar
• ElvidgeSEMA’s parallel advice workshop bridges regulatory and reimbursement divideNat Rev Drug Discov20131318824378785
   PubMed Web of Science ®Google Scholar
• BaghaipourMRSteen CarlssonKStrategies for inhibitor treatment and costs in the short and long term: a critical evaluation of recent clinical studiesEur J Haematol201594Suppl 77303725560792
   PubMed Web of Science ®Google Scholar
• CochraneALEffectiveness and Efficiency: Random Reflections on Health Services [Internet]. Nuffield Provincial Hospitals Trust; 1972 [cited April 16, 2015]. Available from: http://www.nuffieldtrust.org.uk/sites/files/nuffield/publication/Effectiveness_and_Efficiency.pdf Accessed May 25, 2015
   Google Scholar
• HillABThe environment and disease: association or causation?Proc R Soc Med196558529530014283879
   PubMedGoogle Scholar
• Food and Drug AdministrationSummary Basis for Regulatory Action – Treatment of Acute Bleeding in Patients with Congenital Fibrinogen Deficiency, Afibrinogenemia and Hypofibrinogenemia [Internet]; 2009 [cited February 23, 2015]. Available from: http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM244507.pdfAccessed May 25, 2015
   Google Scholar
• European Medicines AgencyScientific Discussion – Novo-seven European Public Assessment Report [Internet]; 2005 [cited February 4, 2015]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000074/WC500030713.pdfAccessed May 25, 2015
   Google Scholar
• AledortLLjungRBlanchetteVOn Behalf of the International Prophylaxis Study Group (IPSG). Are randomized clinical trials the only truth? Not alwaysJ Thromb Haemost20064350350416460429
   PubMed Web of Science ®Google Scholar
• Manco-JohnsonMJAbshireTCShapiroADProphylaxis versus episodic treatment to prevent joint disease in boys with severe hemophiliaN Engl J Med2007357653554417687129
   PubMed Web of Science ®Google Scholar
• Manco-JohnsonMLBladesTAFunkSLong-term orthopedic effects of delaying prophylaxis in severe hemophilia a until age 6 years: results of the joint outcome study continuation (JOSc)Blood201312221210210
   Web of Science ®Google Scholar
• USFDAStatistical Review and Evaluation – Recombinant Factor IX [Internet]; 2012 [cited February 6, 2014]. Available from: http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM363188.pdfAccessed May 25, 2015
   Google Scholar
• SolomonMJust a Paradigm: Evidence-Based Medicine in Epistemological Context2009 [cited November 18, 2013]. Available from: http://philsci-archive.pitt.edu/4793/Accessed May 25, 2015
   Google Scholar
• McMullanVAlstonRPIIIAprotinin and cardiac surgery: a sorry tale of evidence misusedBr J Anaesth2013110567567823599511
   PubMed Web of Science ®Google Scholar
• HébertPCFergussonDAHuttonBRegulatory decisions pertaining to aprotinin may be putting patients at riskCan Med Assoc J2014186181379138625267766
   PubMed Web of Science ®Google Scholar
• WiseJBoldt: the great pretenderBMJ2013346mar19 1f1738f173823512099
   PubMed Web of Science ®Google Scholar
• European Medicines Agency Committee for Proprietary Medicinal ProductsPoints to Consider upon Application with (1) Meta- analysis (2) One Pivotal Study [Internet]; 2011 [cited February 6, 2015]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003657.pdfAccessed May 25, 2015
   Google Scholar
• BrokJThorlundKGluudCWetterslevJTrial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analysesJ Clin Epidemiol200861876376918411040
   PubMed Web of Science ®Google Scholar
• BrougherJTThe Biosimilars Act: promoting or discouraging the development of generic biologics?Biotechnol Healthc201074222322478837
   PubMedGoogle Scholar
• FranchiniMLippiGImmune tolerance induction for patients with severe hemophilia A: a critical literature reviewJ Thromb Thrombolysis201132443944721818664
   PubMed Web of Science ®Google Scholar
• CollinsPWFischerKMorfiniMBlanchetteVSBjörkmanSOn Behalf of International Prophylaxis Study Group (IPSG) Pharmacokinetics Expert Working GroupImplications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophiliaHaemophilia201117121020731726
   PubMed Web of Science ®Google Scholar
• CollinsPWBjörkmanSFischerKFactor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A: influences of variance in pharmacokinetics and treatment regimensJ Thromb Haemost20108226927519943875
   PubMed Web of Science ®Google Scholar
• CollinsPWPersonalized prophylaxisHaemophilia20121813113522726096
   PubMed Web of Science ®Google Scholar
• SchlenkrichSSchubertCSecondary prophylaxis in an adult patient with severe haemophilia A. Factor VIII consumption and effectivenessHamostaseologie201333324124423435748
   PubMed Web of Science ®Google Scholar
• GuyattGHHeytingAJaeschkeRKellerJAdachiJDRobertsRSN of 1 randomized trials for investigating new drugsControl Clin Trials1990112881002161315
   PubMedGoogle Scholar
• KravitzRLDuanNNiedzinskiEJHayMCSubramanianSKWeisnerTSWhatever happened to N-of-1 trials? Insiders’ perspectives and a look to the futureMilbank Q200886453355519120979
   PubMed Web of Science ®Google Scholar
• ScuffhamPANiklesJMitchellGKUsing N-of-1 trials to improve patient management and save costsJ Gen Intern Med201025990691320386995
   PubMed Web of Science ®Google Scholar
• KravitzRLDuanNWhiteRHN-of-1 trials of expensive biological therapiesArch Intern Med2008168101030103318504330
   PubMedGoogle Scholar
• BjörkmanSFolkessonABerntorpEIn vivo recovery of factor VIII and factor IX: intra- and interindividual variance in a clinical settingHaemophilia20071312817212717
   PubMed Web of Science ®Google Scholar
• Den UijlIEMauser BunschotenEPRoosendaalGClinical severity of haemophilia A: does the classification of the 1950s still stand?Haemophilia201117684985321545376
   PubMed Web of Science ®Google Scholar
• KravitzRLDuanNDesign and Implementation of N-of-1 Trials: A User’s Guide [Internet] Agency for Healthcare Research and Quality; 2014. Available from: http://effectivehealthcare.ahrq.gov/ehc/products/534/1844/n-1-trials-report-130213.pdfAccessed May 25, 2015
   Google Scholar
• LindvallKAstermarkJBjörkmanSDaily dosing prophylaxis for haemophilia: a randomized crossover pilot study evaluating feasibility and efficacyHaemophilia201218685585922681244
   PubMed Web of Science ®Google Scholar
• AlameluJBevanDSorensenBRangarajanSPharmacokinetic and pharmacodynamic properties of plasma-derived vs recombinant factor IX in patients with hemophilia B: a prospective crossover studyJ Thromb Haemost201412122044204825315324
   PubMed Web of Science ®Google Scholar
• CollinsPFaradjiAMorfiniMEnriquezMMSchwartzLEfficacy and safety of secondary prophylactic vs on-demand sucrose-formulated recombinant factor VIII treatment in adults with severe hemophilia A: results from a 13-month crossover studyJ Thromb Haemost201081838919817995
   PubMed Web of Science ®Google Scholar
• ZuckerDRSchmidCHMcIntoshMWD’AgostinoRBSelkerHPLauJCombining single patient (N-of-1) trials to estimate population treatment effects and to evaluate individual patient responses to treatmentJ Clin Epidemiol19975044014109179098
   PubMed Web of Science ®Google Scholar
• DuanNKravitzRLSchmidCHSingle-patient (n-of-1) trials: a pragmatic clinical decision methodology for patient-centered comparative effectiveness researchJ Clin Epidemiol2013668 0S21S2823849149
   PubMed Web of Science ®Google Scholar
• KumarDThe personalised medicine. A paradigm of evidence-based medicineAnn Ist Super Sanita2011471314021430336
   PubMed Web of Science ®Google Scholar
• De LeonJEvidence-based medicine versus personalized medicine: are they enemies?J Clin Psychopharmacol201232215316422367661
   PubMed Web of Science ®Google Scholar
• Food and Drug AdministrationGuidance for Industry Adaptive Design Clinical Trials for Drugs and Biologics [Internet]; 2010 [cited February 24, 2015]. Available from: http://www.fda.gov/downloads/Drugs/Guidances/ucm201790.pdfAccessed May 25, 2015
   Google Scholar
• European Medicines AgencyGuideline on Clinical Trials in Small Populations [Internet]; 2005 [cited February 24, 2015]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003615.pdfAccessed May 25, 2015
   Google Scholar
• FaceyKGranadosAGuyattGGenerating health technology assessment evidence for rare diseasesInt J Technol Assess Health Care201430441642225407328
   PubMed Web of Science ®Google Scholar
• Institute for Quality and Efficiency in Health CareGeneral Methods 4.1 [Internet]; 2013 [cited February 24, 2015]. Available from: https://www.iqwig.de/download/IQWiG_General_Methods_Version_%204-1.pdfAccessed May 25, 2015
   Google Scholar
• SackettDLRosenbergWMCGrayJAMHaynesRBRichardsonWSEvidence based medicine: what it is and what it isn’tBMJ1996312702371728555924
   PubMed Web of Science ®Google Scholar
• Cochrane CollaborationOur Strategy [Internet]; 2015 [cited February 11, 2015]. Available from: http://www.cochrane.org/about-us/our-strategyAccessed May 25, 2015
   Google Scholar
• CoppolaAWindygaJTufanoAYeungCDi MinnoMNDTreatment for preventing bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgeryThe Cochrane CollaborationCochrane Database of Systematic Reviews [Internet]Chichester, UKJohn Wiley and Sons, Ltd2015 [cited February 10, 2015]. Available from: http://www.cochrane.org/CD009961/CF_preventing-bleeding-in-people-with-congenital-bleeding-disorders-during-and-after-surgeryAccessed May 25, 2015
   Google Scholar
• IorioAMarchesiniEMarcucciMStobartKChanAKClotting factor concentrates given to prevent bleeding and bleeding-related complications in people with hemophilia A or BThe Cochrane CollaborationCochrane Database of Systematic Reviews [Internet]Chichester, UKJohn Wiley and Sons, Ltd2011 [cited February 10, 2015]. Available from: http://www.cochrane.org/CD003429/CF_regular-clotting-factor-replacement-therapy-to-prevent-joint-disease-in-people-with-severe-hemophilia-a-or-bAccessed May 25, 2015
   Google Scholar
• GøtzschePCJohansenHKIntravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung diseaseThe Cochrane CollaborationCochrane Database of Systematic Reviews [Internet]Chichester, UKJohn Wiley and Sons, Ltd2010 [cited February 10, 2015]. Available from: http://www.cochrane.org/CD007851/AIRWAYS_intravenous-alpha-1-antitrypsin-augmentation-therapy-for-treating-patients-with-alpha-1-antitrypsin-deficiency-and-lung-diseaseAccessed May 25, 2015
   Google Scholar
• ShenL-JChouHHuangC-FChouG-MChanWKWuF-LLEconomic benefits of sponsored clinical trials on pharmaceutical expenditures at a medical center in TaiwanContemp Clin Trials201132448549121530679
   PubMed Web of Science ®Google Scholar
• GrossiFGenovaCGaitanNDFree drugs in clinical trials and their potential cost saving impact on the National Health Service: a retrospective cost analysis in ItalyLung Cancer201381223624023648072
   PubMed Web of Science ®Google Scholar
• US National Institutes of HealthSearch for Factor VIII AND Hemophilia [Internet]; 2015 [cited February 25, 2015]. Available from: https://clinicaltrials.gov/ct2/results?term=Factor+VIII+AND+hemophilia&Search=SearchAccessed May 25, 2015
   Google Scholar
• European Medicines AgencyEMA-HTA Workshop Bringing Together Stakeholders for Early Dialogue in Medicines Development – Report from the Public Workshop Hosted by the European Medicines Agency (EMA) in London on 26 November 2013 [Internet]; 2014 [cited February 13, 2015]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2014/05/WC500166228.pdfAccessed May 25, 2015
   Google Scholar
• SingalAGHigginsPDRWaljeeAKA primer on effectiveness and efficacy trialsClin Transl Gastroenterol201451e4524384867
   PubMed Web of Science ®Google Scholar
• WhiteheadSJAliSHealth outcomes in economic evaluation: the QALY and utilitiesBr Med Bull201096152121037243
   PubMed Web of Science ®Google Scholar
• CaroJJNordESiebertUThe efficiency frontier approach to economic evaluation of health-care interventionsHealth Econ201019101117112720575151
   PubMed Web of Science ®Google Scholar
• European Network of HTA AgenciesHTA Core Model [Internet]; 2014 [cited February 13, 2015]. Available from: http://meka.thl.fi/htacore/model/AE-tables-pharma-2.0.pdfAccessed May 25, 2015
   Google Scholar
• Finnish Office for Health Technology AssessmentAssessment ElementTables for HTA Core Model Application for Diagnostic Technologies [Internet]; 2014 [cited February 25, 2015]. Available from: http://meka.thl.fi/htacore/model/AE-tables-diagnostics-2.0.pdfAccessed May 25, 2015
   Google Scholar
• BarnettDThe HTA View [Internet]. EMA-HTA Workshop Parallel Advice in Scientific Drug Development, London UK; 2013 [cited February 25, 2015]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Presentation/2013/11/WC500155669.pdfAccessed May 25, 2015
   Google Scholar
• European Medicines AgencyReflection Paper on the Regulatory Guidance For the Use of Health related Quality of Life (HRQL) Measures in the Evaluation of Medicinal Products [Internet]; 2005 [cited February 25, 2015]. Available from: http://www.ispor.org/workpaper/emea-hrql-guidance.pdfAccessed May 25, 2015
   Google Scholar
• Centre for Innovation in Regulatory Science, LtdNew Drug Approvals in ICH Countries 2003–20 [Internet]; 2013 [cited February 25, 2015]. Available from: http://www.cirsci.org/sites/default/files/CIRS_R&D_Briefing_52_May_2013.pdfAccessed May 25, 2015
   Google Scholar
• BerntorpEAstermarkJBaghaeiFTreatment of haemophilia A and B and von Willebrand’s disease: summary and conclusions of a systematic review as part of a Swedish health-technology assessmentHaemophilia201218215816522151198
   PubMed Web of Science ®Google Scholar
• O’MahonyBNooneDGiangrandePLFPrihodovaLHaemophilia care in Europe: a survey of 19 countriesHaemophilia2011171354020722746
   PubMed Web of Science ®Google Scholar
• FarrugiaAHermansCFranchiniMAssessing options for treating haemophilia with inhibitorsHaemophilia2015
   Web of Science ®Google Scholar
• IQWIG[A13-07] Treatment of Haemophilia Patients – Rapid Report [Internet]; 2012 [cited February 25, 2015]. Available from: https://www.iqwig.de/en/projects-results/projects/drug-assessment/a13-07-treatment-of-haemophilia-patients-rapid-report.3253.html#overviewAccessed May 25, 2015
   Google Scholar
• Gemeinsamer BundesausschussBeschluss des Gemeinsamen Bundesausschusses über eine Änderung der Arzneimittel-Richtlinie (AM-RL): Anlage XII – Beschlüsse über die Nutzenbewertung von Arzneimitteln mit neuen Wirkstoffen nach § 35a SGB V – Turoctocog alfa (Decision [Federal Joint Committee] of the Federal Joint Committee amending the Prescription Drug Guidelines (AM-RL): Appendix XII – Decisions on the benefit assessment of drugs with new active substances in accordance with § 35a SGB V [Social Security Code V] – Turoctocog Alfa) [Internet]; 2014 [cited February 25, 2015]. Available from: https://www.g-ba.de/downloads/39-261-2026/2014-07-03_AM-RL-XII_Turoctocog%20alfa_2014-01-15-D-092_BAnz.pdfAccessed May 25, 2015
   Google Scholar
• Gemeinsamer BundesausschussTragende Gründe 1 zum Beschlussentwurf des Gemeinsamen Bundesausschusses über eine Änderung der Arzneimittel-Richtlinie (AM-RL): Anlage XII – Beschlüsse über die Nutzenbewertung von Arzneimitteln mit neuen Wirkstoffen nach § 35a SGB V – Turoctocog alfa (Justification [Federal Joint Committee] of the Decision of the Federal Joint Committee amending the Prescription Drug Guidelines (AM-RL): Appendix XII – Decision on the Benefit Assessment of Drugs with New Active Substances in accordance with § 35a SGB V [Social Security Code V] – Turoctocog Alfa) [Internet]; 2014 [cited February 25, 2015]. Available from: https://www.g-ba.de/downloads/40-268-2871/2014-07-03_AM-RL-XII_Turoctocog%20alfa_2014-01-15-D-092_TrG.pdfAccessed May 25, 2015
   Google Scholar
• IQWIGSimoctocog Alfa for Haemophilia A: No Suitable Data [Internet]; 2015 [cited March 6, 2015]. Available from: https://www.iqwig.de/en/press/press-releases/press-releases/simoctocog-alfa-for-haemophilia-a-no-suitable-data.6593.htmlAccessed May 25, 2015
   Google Scholar
• RuggeriKNolteEPharmaceutical Pricing – The Use of External Reference Pricing Internet2013 Available from: http://www.rand.org/content/dam/rand/pubs/research_reports/RR200/RR240/RAND_RR240.pdfAccessed May 25, 2015
   Google Scholar
• PetkantchinVEconomic Effects of Germany’s Reference Pricing Policy for Drugs [Internet]; 2006 [cited February 26, 2015]. Available from: http://www.institutmolinari.org/economic-effects-of-germany-s,491.htmlAccessed May 25, 2015
   Google Scholar
• PowellJSPasiKJRagniMVPhase 3 study of recombinant factor IX Fc fusion protein in hemophilia BN Engl J Med2013369242313232324304002
   PubMed Web of Science ®Google Scholar
• MahlanguJPowellJSRagniMVPhase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia ABlood2014123331732524227821
   PubMed Web of Science ®Google Scholar
• Food and Drug AdministrationRixubis – Statistical Review and Evaluation [Internet]; 2012 [cited February 26, 2015]. Available from: http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM363882.pdfAccessed May 25, 2015
   Google Scholar
• Manco-JohnsonMJKemptonCLRedingMTRandomized, controlled, parallel-group trial of routine prophylaxis vs on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A (SPINART)J Thromb Haemost20131161119112723528101
   PubMed Web of Science ®Google Scholar
• Food and Drug AdministrationSummary Basis for Regulatory Action – Novoeight/Antihemophilic Factor (Recombinant) [Internet]; 2013 [cited February 26, 2015]. Available from: http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM373769.pdfAccessed May 25, 2015
   Google Scholar
• CSLBehringA Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIXFP) in Patients with Hemophilia B [Internet]; 2015 [cited February 26, 2015]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT01496274?term=Factor+IX+CSL&rank=3Accessed May 25, 2015
   Google Scholar
• BayerA Trial to Compare Prophylaxis Therapy to On-demand Therapy with a New Full Length Recombinant FVIII in Patients with Severe Hemophilia A (Leopold II) [Internet]; 2014 [cited April 12, 2015]. Available from: https://clinicaltrials.gov/ct2/show/results/NCT01233258?term=Bayer+Factor+VIII&rank=22Accessed May 25, 2015
   Google Scholar
• BayerA Trial Investigating Safety and Efficacy of Treatment with BAY94-9027 in Severe Hemophilia A (PROTECT-VIII) [Internet]; 2015 [cited April 12, 2015]. Available from: https://clinicaltrials.gov/ct2/show/NCT01580293?term=BAY+94-9027&rank=3Accessed May 25, 2015
   Google Scholar
• BaxterStudy Investigating a PEGylated Recombinant Factor VIII (BAX 855) for Hemophilia A (PROLONG-ATE Study) [Internet]; 2014 [cited April 12, 2015]. Available from: https://clinicaltrials.gov/ct2/show/NCT01736475?term=BAX+855&rank=2Accessed May 25, 2015
   Google Scholar
• OctapharmaEfficacy and Safety Study of Human-cl rhFVIII in PTPs With Severe Hemophilia A [Internet]; 2013 [cited April 12, 2015]. Available from: https://clinicaltrials.gov/ct2/show/study/NCT01125813?term=GENA-08&rank=1&sect=X01256Accessed May 25, 2015
   Google Scholar
• NovonordiskEvaluation of Safety and Efficacy, Including Pharmacokinetics, of NNC 0129-0000-1003 When Administered for Treatment and Prophylaxis of Bleeding in Subjects with Haemophilia A (pathfinderTM2) [Internet]; 2015 [cited April 12, 2015]. Available from: https://clinicaltrials.gov/ct2/show/NCT01480180?term=N8-GP&rank=3Accessed May 25, 2015
   Google Scholar
• NovonordiskSafety and Efficacy of Nonacog Beta Pegol (N9-GP) in Previously Untreated Patients with Haemophilia B (paradigmTM6) [Internet]; 2015 [cited April 12, 2015]. Available from: https://clinicaltrials.gov/ct2/show/NCT02141074?term=N9-GP&rank=1Accessed May 25, 2015
   Google Scholar
• CSLBehringAn Open-label Safety and Efficacy Study of Recombinant FVIII in Patients with Severe Hemophilia A [Internet]; 2015 [cited April 12, 2015]. Available from: https://clinicaltrials.gov/ct2/show/NCT02172950?term=rVIII-SingleChain&rank=2Accessed May 25, 2015
   Google Scholar
• KleinHOptimal Clinical Use of Blood and Plasma Derivatives Background and Perspectives [Internet]. Optimal Use of Coagulation Factors and Immunoglobulins Meeting, Wildbad Kreuth, Bavaria, Germany; 2013 [cited February 26, 2015]. Available from: https://www.edqm.eu/medias/fichiers/session_1.pdfAccessed May 25, 2015
   Google Scholar
• Manco-JohnsonMJKemptonCLRedingMTRandomized, controlled, parallel-group trial of routine prophylaxis vs on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A (SPINART)J Thromb Haemost20131161119112723528101
   PubMed Web of Science ®Google Scholar
• FreedmanBEquipoise and the ethics of clinical researchN Engl J Med198731731411453600702
   PubMed Web of Science ®Google Scholar
• GringeriALundinBvon MackensenSMantovaniLMannucciPMESPRIT Study GroupA randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study)J Thromb Haemost20119470071021255253
   PubMed Web of Science ®Google Scholar
• MannHLondonAJMannJEquipoise in the enhanced suppression of the platelet IIb/IIIa receptor with integrilin trial (ESPRIT): a critical appraisalClin Trials20052323324316279146
   PubMed Web of Science ®Google Scholar
• TchengJEMadanMO’SheaJCEthics and equipoise: rationale for a placebo-controlled study design of platelet glycoprotein IIb/IIIa inhibition in coronary interventionJ Interv Cardiol20031629710512768912
   PubMedGoogle Scholar
• FreedmanBPlacebo-controlled trials and the logic of clinical purposeIRB19901261611651265
   PubMedGoogle Scholar
• World Medical AssociationWorld Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects [Internet]; 2008 [cited February 26, 2015]. Available from: http://www.wma.net/en/30publications/10policies/b3/17c.pdfAccessed May 25, 2015
   Google Scholar
• GoodyearMDELemmensTSprumontDTangwaGDoes the FDA have the authority to trump the Declaration of Helsinki?BMJ2009338b155919383751
   PubMed Web of Science ®Google Scholar
• International Conference on HarmonizationICH Harmonised Tripartite Guideline for Good Clinical Practice [Internet]; 1996 [cited February 26, 2015]. Available from: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdfAccessed May 25, 2015
   Google Scholar
• MannucciPMEvolution of the European guidelines for the clinical development of factor VIII products: little progress towards improved patient managementHaemophilia201319334434823088389
   PubMed Web of Science ®Google Scholar