Strategies for Comparative Efficacy Trials


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Strategies for Comparative Efficacy Trials

  1. 1. Strategies for Comparative Efficacy TrialsReport Details:Published:August 2012No. of Pages: 81Price: Single User License – US$3800Clinicians and patients want to be able to compare new drugs with those already available toinform evidence-based medicine, and reimbursement authorities require comparative data tosupport their decisions. This report discusses the role of comparative efficacy trials and thechallenges in their design, with particular attention to the question of comparator selection.Features and benefits•Understand the role that comparative efficacy plays in the evaluation of new drugs.•Review the various types of trial design that can provide comparative data and assess the purpose for which each is most suited.•Identify decision-making processes for guiding key choices in the design of pivotal comparative efficacy trials.•Understand the importance of comparator selection and the consequences of later disagreements with external authorities.•Review the factors that need to be considered in making a comparator selection.HighlightsThe choice of active control group for a comparative trial can be difficult due to variation in thestandard of care across different geographic regions and changing medical practices.Numerous recent appraisals by the UK’s National Institute for Health and Clinical Excellence(NICE) and Germany’s Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG)have demonstrated the critical stance that is being readily taken by these bodies with regard tocomparator selection.Scientific advice from regulators and, where possible, from health technology assessors orreimbursement authorities can be extremely useful in guiding clinical development planning,especially in the choice of comparator.Your key questions answered•What is driving the use of comparative efficacy trials and what role do they play in approval and reimbursement decisions?
  2. 2. •How should an active comparator and other features of comparative efficacy trials be chosen?•Can the range of comparators be expected to extend beyond pharmaceutical interventions?•Which regulatory and reimbursement authorities are willing to offer scientific advice in the design of a comparative efficacy trial?•To what extent have drug evaluation committees shown flexibility in disagreements about the optimum comparator?Get your copy of this report @ points covered in Table of Contents of this report includeTable Of ContentsEXECUTIVE SUMMARYKey findingsThe impetus to conduct comparative efficacy trialsSummaryAvailability of comparative data during regulatory reviewAddressing uncertaintyFDAEMADifferences in approach in the US and EUResearch ethicsEfficacy or effectiveness: when should comparative trials be conducted?Case study: antihypertensivesClinical trial designsSummaryIntroductionSuperiority trialsNon-inferiority trialsFDA versus EMA guidanceComparative efficacy and biocreepThree-arm trialsAdaptive trialsSubgroup analysisCase study: subgroup analysis within a non-inferiority trialPlacebo effectsBiosimilarsPragmatic clinical trialsObservational studies
  3. 3. Network meta-analysesSimultaneous consideration of benefits and harmsConclusionsTrial optimizationSummaryIntroductionRecent examples of challenges in comparator selectionAstraZeneca’s Faslodex rejected by NICE on the basis of indirect comparisonIQWiG and NICE judge GlaxoSmithKline’s Benlysta to have been inadequately comparedBiogen Idec’s Fampyra highlights challenges of comparison with non-pharmacological treatmentIQWiG disagrees with GlaxoSmithKline regarding comparators for TrobaltEisai’s Halaven considered inadequately compared despite following EMA protocolComparison with experimental treatments not demanded by the FDA but view of reimbursers isuncertainA late-arriving statin has adequate comparator data for regulatory approval but provingdifferentiation is another matterSelection of active control group for the comparative trialUse of existing knowledgeDecision-making techniquesReflecting on the range of interventionsPatient populations, outcomes, and other study variablesScientific adviceConclusionsOutlookSummaryIntroductionComparative efficacy: a regulatory requirement?Regulators and reimbursement authorities: working togetherProgressive approvalsConclusionAppendixMethodologyAcknowledgementsGlossaryAbbreviationsReferencesDisclaimerList Of Tables
  4. 4. Table: New medicines with premarketing randomized active-controlled trials (1995–2005)Table: New medicines without premarketing randomized active-controlled trials (1995–2005)Table: Trials described in approval packages in the US and EU (2005–07)Table: Comparator information available for drugs approved in the EU (2009–10)Table: New medicines (1999–2005) with an improved efficacyTable: Therapeutic areas in which response to placebo varies widely between trialsTable: Advantages and disadvantages of using adaptive clinical trial designsTable: Sample sizes for a three-arm randomized controlled trial or an adaptive Phase III/IV trialTable: Possible trial designs providing comparative efficacy dataTable: Possible trial designs providing comparative effectiveness dataTable: Statins available in the USTable: Scenarios for requirements for comparative efficacy in regulatory approvalTable: The future role of The Joint Initiative for Medicines: coordinating the EMA, HTA, andcompetent bodiesList Of FiguresFigure: New molecular entities with comparative efficacy data available in FDA approval packages(2000–10)Figure: Recommendations from the Presidential Commission for the Study of Bioethical IssuesFigure: Defining efficacy and effectivenessFigure: Designs of studies for efficacy and effectivenessFigure: Adaptive Phase III/IV trial designFigure: Factors determining choice of active control in a clinical trialFigure: Effects of increased calls for comparative efficacy trials on drug developmentContact: for more information.