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Indirect Comparisions Presented In German Benefit Assessments – Status Quo and Quo Vadis?
A694
VA L U E I N H E A LT H 2 0 ( 2 0 1 7 ) A 3 9 9 – A 8 1 1
(network) meta-analysis (NMA) or indirect treatment comparison (ITC) techniques is recommended. This review aimed to determine how Evidence Review Groups (ERGs) perceived National Institute for Health and Care Excellence (NICE) single technology appraisals (STAs) in the absence of these established methods. Methods: STA manufacturer submissions from 2015 onwards, excluding terminated appraisals and reappraisals, were screened in June 2017. Submissions that did not conduct any conventional comparisons were eligible for inclusion. The rationale for not using conventional methodology, the use of non-conventional techniques and the corresponding ERG critiques were reviewed. Results: Of the 72 submissions screened, 24 were ultimately included. In just under half of the included submissions, the primary reason for not conducting a meta-analysis was reported to be that only a single relevant RCT was identified, whilst the primary reason cited for not conducting an ITC or NMA in almost a third of the submissions was between-study heterogeneity. The ERGs concluded that conventional comparisons could have been conducted for five submissions, and performed their own meta-analysis in one case. Only six submissions used non-conventional methods to perform a comparison, including naïve comparisons only (n= 2), adjusted comparison methods (n= 3) and meta-analysis using single-arm trial data (n= 1). The ERGs were largely receptive of these non-conventional methods and acknowledged the data limitations; all six submissions were recommended. Ultimately, 22 of the included submissions received a positive recommendation from NICE. Conclusions: A third of the STA submissions reviewed did not include a conventional comparison, usually due to limited data availability or between-study heterogeneity. However, ERGs were generally receptive if a robust search strategy and full exploration of the evidence had been undertaken, and the majority of submissions lacking conventional comparisons were ultimately recommended. PHP242 Indirect Comparisions Presented In German Benefit Assessments – Status Quo and Quo Vadis? Kreisor M, Schiffter-Weinle HA, Boehler Y TH Koeln, University of Applied Sciences, Leverkusen, Germany
Objectives: German benefit assessments on drugs evaluate added benefit against the appropriate comparator, which is determined by G-BA. If a direct comparison between new drug and comparator is not available, an indirect comparison may be submitted by the manufacturer. This is evaluated during assessment by IQWiG/G-BA. The aim of this study is to provide a comprehensive overview on how indirect comparisons were evaluated in German benefit assessments until today. Methods: All documents were retrieved from the G-BA homepage. Cut-off date for inclusion was September 1st 2016 (poster will include an update). The following sources had to be available: Dossier module 4 (manufacturers), benefit assessment (IQWiG, if applicable), G-BA decision/rationale (G-BA). Extraction included indirect comparisons submitted by manufacturers and added benefit claimed, IQWiG/G-BA evaluation of indirect comparison and added benefit. Results: 202 benefit assessments were reviewed. Of these, 41 assessments contained 51 indirect comparisons. Manufacturers rated extent and probability of the added benefit higher than IQWiG/G-BA. Extent was rated “considerable” in 17 cases and probability was rated as “hint” in 16 cases, only 3 indirect comparisons were not used to support added benefit. IQWiG declined 40 indirect comparisons and accepted only 6. In 45 assessments added benefit was rated “not proven”. G-BA declined 38 comparisons, accepted 5 fully and 3 partially. Added benefit was rated “not proven” for 43 assessments. IQWiG/G-BA declined mainly due to inadequate methods, study populations or comparators. Only one assessment (Empagliflozin, start March 1st 2016) succeeded with an added benefit based on a partially accepted indirect comparison. Conclusions: Evaluations of indirect comparisons by manufacturers and IQWiG/G-BA differ considerably. So far indirect comparisons are no promising tool for achieving added benefit. However, being successful is at least possible. Developing and applying sound methods is key, as well as a strict interpretation of study populations and comparators. PHP243 A Comparative Review of Value Assessment Frameworks In Germany, France, England, Australia, and South Korea: An Industry Perspective Campbell PR1, Gaebler JA1, Boylston M1, Michas Z1, Koo BJ1, Funderburk A1, Haninger K2, Grainger D2 1Health Advances, Weston, MA, USA, 2Pharmaceutical Research and Manufacturers of America (PhRMA), Washington, DC, USA
Objectives: Many countries utilize Value Assessment Frameworks (VAF) or Health Technology Assessments (HTA) to inform market access and reimbursement for innovative medicines. We sought to characterize the absolute and relative strengths, challenges, and limitations of five well-established VAFs from the perspective of the biopharmaceutical industry, and to determine if each VAF’s stated objectives aligned with observed reimbursement outcomes. Methods: For each country’s VAF, we first reviewed published documentation (government websites, peerreviewed literature) to capture stated principles and procedures of assessment, appraisal, and pricing. We then qualitatively ranked the VAFs on scales of: transparency (regarding data requirements, published assessment outcomes, translation of value into price); flexibility (in comparator selection and consideration of nonRCT data); stakeholder engagement (influence of patients, industry, and clinicians in the assessment process); access to innovative medicines. Initial rankings were refined based on double-blinded interviews with 40 executives from biopharmaceutical companies, country trade association representatives, and HTA thought leaders. Finally, we conducted a precedent analysis of reimbursement outcomes for 12 recently launched innovative medicines that had been reviewed by multiple VAFs and represented a range of therapeutic areas. Results: England rated highest relative to other VAFs on stakeholder engagement and flexibility of comparator and data requirements, while Germany fared best on patient access to innovative medicines across therapeutic areas. France, South Korea, and Australia were more
likely to delay access to rare disease and oncology therapies. Though more opaque in how assessments translated to reimbursement, interviewees noted a preference for the “added clinical benefit” VAFs in France and Germany, compared with ICERbased VAFs. Conclusions: The innovative biopharmaceutical industry recognizes relative advantages and drawbacks of established VAFs, and its assessments are supported by empiric reimbursement outcomes across therapeutic areas. Countries interested in attracting multinational pharmaceutical investment and products should understand the nuances and lessons of established systems before imposing new VAF processes. PHP244 Early Scientific Advice At Cadth – Options and Recommendations For Future Development Husereau D1, Sood AR2 1Institute of Health Economics, Ottawa, ON, Canada, 2Canadian Agency for Drugs and Technologies in Health, Ottawa, ON, Canada
Objectives: : Early Scientific Advice at CADTH was developed in response to a perceived need by innovators and modeled after similar programs internationally. It was developed with the principles that advice on early drug development plans will help produce a more complete package of evidence for reimbursement, and with the goals of reducing uncertainty for payers and providing more timely access for patients. The purpose of this qualitative study was to gauge industry stakeholder awareness of the initiative, and what changes within the scope or mandate of the program may make it more useful and accessible. Methods: : Semi-structured interviews were conducted with representatives of pharmaceutical companies. Interviews were conducted by a consultant via telephone and written notes were sent back to each participant with instructions to review for accuracy and make modifications as necessary. Comments were aggregated into themes. Results: : Among 26 companies contacted, 16 completed an interview. The interview sample consisted of 4 small companies (≤ 10,000 employees globally), 6 large US-based companies, and 6 large non-US-based companies. Two of the interviewees were global representatives. Most interviewees were aware of the CADTH Scientific Advice program. Major themes that emerged with regards to suggested improvements to the program included the following: expand the scope of the program to include advice after initiation of Phase III trials; provide advice on real-world evidence study designs; allow for disclosure of advice received at the time of submission for reimbursement review; provide quick access to smaller requests for advice; offer parallel advice with a regulator or with other HTA agencies. Conclusions: The findings from this study will help inform improvements to the Scientific Advice program at CADTH. They may also inform other HTA agencies with similar existing programs as well as those developing Scientific Advice programs currently. PHP245 How Will Proposed Changes To The Nice Highly Specialised Technology Evaluation Process Impact Patient Access To Innovative Drugs for Rare Diseases? Nicholson L, Fountain DL, Longworth L, Adkins E PHMR Ltd, London, UK
Objectives: Health technology assessments of ultra-orphan drugs (ultra-ODs) for very rare conditions are faced with several unique challenges. In recognition of this, in 2016–17 the National Institute for Health and Care Excellence (NICE) proposed new initiatives to its Highly Specialised Technology (HST) programme, including introduction of a cost-per-QALY threshold. The objective of this study was to evaluate HST evaluations in the context of the proposed changes and the potential impact they may have on patient access to ultra-ODs in England and Wales. Methods: All publicly available HST evaluations published between its inception in April 2013 and June 2017 were reviewed, alongside guidance relating to the proposed changes. Results: Six HST evaluations had been conducted by NICE and seven were in development. Five received positive reimbursement decisions with a cost per treatment/year of £125,000–£394,680. One (sebelipase alfa) was not recommended based on the prohibitively expensive cost (£491,992 per treatment/year), in the context of uncertainties around the long-term benefits. All positive recommendations have conditions attached, including a patient access scheme (eculizumab, ataluren, migalastat), managed access scheme (ataluren, elosulfase alfa), and use within expert centres (eculizumab). The proposed changes to the HST programme include implementing a cost-effectiveness threshold for ultra-ODs of £100,000–£300,000 per QALY, using a QALY weighting based on the number of additional QALYs a medicine offers. Under the proposed changes those ultra-ODs with a positive recommendation would be unlikely to significantly raise the £100,000 threshold, and therefore may not receive a positive recommendation without a patient access scheme or managed access scheme to improve costeffectiveness. Conclusions: The introduction of a cost-effectiveness threshold increases clarity about decisions regarding which ultra-ODs are routinely funded, but could make patient access more difficult as they may be less likely to be recommended by NICE. PHP246 Reviewing The Effectiveness of Uk Drug Horizon Scanning Efforts & The Production of Nice Commentary Along Therapeutic Specialties Woltmann JD National Institute for Health Research Innovation Observatory, Newcastle upon Tyne, UK
Objectives: The National Institute for Health Research Innovation Observatory is responsible for notifying the National Institute for Health & Clinical Excellence (NICE) of new drugs & indications prior to market authorisation (MA). This constitutes the first step in NICE’s topic selection, and the desired notification period is 600 days for new drugs, 450 for new indications. This research aims to explore the success of previous horizon scanning at meeting notification requirements as well as the speed at which NICE commentary was produced. Methods: All publically available NIHR horizon briefs between 2006 and Q12017 were collated and segmented by
VA L U E I N H E A LT H 2 0 ( 2 0 1 7 ) A 3 9 9 – A 8 1 1
(network) meta-analysis (NMA) or indirect treatment comparison (ITC) techniques is recommended. This review aimed to determine how Evidence Review Groups (ERGs) perceived National Institute for Health and Care Excellence (NICE) single technology appraisals (STAs) in the absence of these established methods. Methods: STA manufacturer submissions from 2015 onwards, excluding terminated appraisals and reappraisals, were screened in June 2017. Submissions that did not conduct any conventional comparisons were eligible for inclusion. The rationale for not using conventional methodology, the use of non-conventional techniques and the corresponding ERG critiques were reviewed. Results: Of the 72 submissions screened, 24 were ultimately included. In just under half of the included submissions, the primary reason for not conducting a meta-analysis was reported to be that only a single relevant RCT was identified, whilst the primary reason cited for not conducting an ITC or NMA in almost a third of the submissions was between-study heterogeneity. The ERGs concluded that conventional comparisons could have been conducted for five submissions, and performed their own meta-analysis in one case. Only six submissions used non-conventional methods to perform a comparison, including naïve comparisons only (n= 2), adjusted comparison methods (n= 3) and meta-analysis using single-arm trial data (n= 1). The ERGs were largely receptive of these non-conventional methods and acknowledged the data limitations; all six submissions were recommended. Ultimately, 22 of the included submissions received a positive recommendation from NICE. Conclusions: A third of the STA submissions reviewed did not include a conventional comparison, usually due to limited data availability or between-study heterogeneity. However, ERGs were generally receptive if a robust search strategy and full exploration of the evidence had been undertaken, and the majority of submissions lacking conventional comparisons were ultimately recommended. PHP242 Indirect Comparisions Presented In German Benefit Assessments – Status Quo and Quo Vadis? Kreisor M, Schiffter-Weinle HA, Boehler Y TH Koeln, University of Applied Sciences, Leverkusen, Germany
Objectives: German benefit assessments on drugs evaluate added benefit against the appropriate comparator, which is determined by G-BA. If a direct comparison between new drug and comparator is not available, an indirect comparison may be submitted by the manufacturer. This is evaluated during assessment by IQWiG/G-BA. The aim of this study is to provide a comprehensive overview on how indirect comparisons were evaluated in German benefit assessments until today. Methods: All documents were retrieved from the G-BA homepage. Cut-off date for inclusion was September 1st 2016 (poster will include an update). The following sources had to be available: Dossier module 4 (manufacturers), benefit assessment (IQWiG, if applicable), G-BA decision/rationale (G-BA). Extraction included indirect comparisons submitted by manufacturers and added benefit claimed, IQWiG/G-BA evaluation of indirect comparison and added benefit. Results: 202 benefit assessments were reviewed. Of these, 41 assessments contained 51 indirect comparisons. Manufacturers rated extent and probability of the added benefit higher than IQWiG/G-BA. Extent was rated “considerable” in 17 cases and probability was rated as “hint” in 16 cases, only 3 indirect comparisons were not used to support added benefit. IQWiG declined 40 indirect comparisons and accepted only 6. In 45 assessments added benefit was rated “not proven”. G-BA declined 38 comparisons, accepted 5 fully and 3 partially. Added benefit was rated “not proven” for 43 assessments. IQWiG/G-BA declined mainly due to inadequate methods, study populations or comparators. Only one assessment (Empagliflozin, start March 1st 2016) succeeded with an added benefit based on a partially accepted indirect comparison. Conclusions: Evaluations of indirect comparisons by manufacturers and IQWiG/G-BA differ considerably. So far indirect comparisons are no promising tool for achieving added benefit. However, being successful is at least possible. Developing and applying sound methods is key, as well as a strict interpretation of study populations and comparators. PHP243 A Comparative Review of Value Assessment Frameworks In Germany, France, England, Australia, and South Korea: An Industry Perspective Campbell PR1, Gaebler JA1, Boylston M1, Michas Z1, Koo BJ1, Funderburk A1, Haninger K2, Grainger D2 1Health Advances, Weston, MA, USA, 2Pharmaceutical Research and Manufacturers of America (PhRMA), Washington, DC, USA
Objectives: Many countries utilize Value Assessment Frameworks (VAF) or Health Technology Assessments (HTA) to inform market access and reimbursement for innovative medicines. We sought to characterize the absolute and relative strengths, challenges, and limitations of five well-established VAFs from the perspective of the biopharmaceutical industry, and to determine if each VAF’s stated objectives aligned with observed reimbursement outcomes. Methods: For each country’s VAF, we first reviewed published documentation (government websites, peerreviewed literature) to capture stated principles and procedures of assessment, appraisal, and pricing. We then qualitatively ranked the VAFs on scales of: transparency (regarding data requirements, published assessment outcomes, translation of value into price); flexibility (in comparator selection and consideration of nonRCT data); stakeholder engagement (influence of patients, industry, and clinicians in the assessment process); access to innovative medicines. Initial rankings were refined based on double-blinded interviews with 40 executives from biopharmaceutical companies, country trade association representatives, and HTA thought leaders. Finally, we conducted a precedent analysis of reimbursement outcomes for 12 recently launched innovative medicines that had been reviewed by multiple VAFs and represented a range of therapeutic areas. Results: England rated highest relative to other VAFs on stakeholder engagement and flexibility of comparator and data requirements, while Germany fared best on patient access to innovative medicines across therapeutic areas. France, South Korea, and Australia were more
likely to delay access to rare disease and oncology therapies. Though more opaque in how assessments translated to reimbursement, interviewees noted a preference for the “added clinical benefit” VAFs in France and Germany, compared with ICERbased VAFs. Conclusions: The innovative biopharmaceutical industry recognizes relative advantages and drawbacks of established VAFs, and its assessments are supported by empiric reimbursement outcomes across therapeutic areas. Countries interested in attracting multinational pharmaceutical investment and products should understand the nuances and lessons of established systems before imposing new VAF processes. PHP244 Early Scientific Advice At Cadth – Options and Recommendations For Future Development Husereau D1, Sood AR2 1Institute of Health Economics, Ottawa, ON, Canada, 2Canadian Agency for Drugs and Technologies in Health, Ottawa, ON, Canada
Objectives: : Early Scientific Advice at CADTH was developed in response to a perceived need by innovators and modeled after similar programs internationally. It was developed with the principles that advice on early drug development plans will help produce a more complete package of evidence for reimbursement, and with the goals of reducing uncertainty for payers and providing more timely access for patients. The purpose of this qualitative study was to gauge industry stakeholder awareness of the initiative, and what changes within the scope or mandate of the program may make it more useful and accessible. Methods: : Semi-structured interviews were conducted with representatives of pharmaceutical companies. Interviews were conducted by a consultant via telephone and written notes were sent back to each participant with instructions to review for accuracy and make modifications as necessary. Comments were aggregated into themes. Results: : Among 26 companies contacted, 16 completed an interview. The interview sample consisted of 4 small companies (≤ 10,000 employees globally), 6 large US-based companies, and 6 large non-US-based companies. Two of the interviewees were global representatives. Most interviewees were aware of the CADTH Scientific Advice program. Major themes that emerged with regards to suggested improvements to the program included the following: expand the scope of the program to include advice after initiation of Phase III trials; provide advice on real-world evidence study designs; allow for disclosure of advice received at the time of submission for reimbursement review; provide quick access to smaller requests for advice; offer parallel advice with a regulator or with other HTA agencies. Conclusions: The findings from this study will help inform improvements to the Scientific Advice program at CADTH. They may also inform other HTA agencies with similar existing programs as well as those developing Scientific Advice programs currently. PHP245 How Will Proposed Changes To The Nice Highly Specialised Technology Evaluation Process Impact Patient Access To Innovative Drugs for Rare Diseases? Nicholson L, Fountain DL, Longworth L, Adkins E PHMR Ltd, London, UK
Objectives: Health technology assessments of ultra-orphan drugs (ultra-ODs) for very rare conditions are faced with several unique challenges. In recognition of this, in 2016–17 the National Institute for Health and Care Excellence (NICE) proposed new initiatives to its Highly Specialised Technology (HST) programme, including introduction of a cost-per-QALY threshold. The objective of this study was to evaluate HST evaluations in the context of the proposed changes and the potential impact they may have on patient access to ultra-ODs in England and Wales. Methods: All publicly available HST evaluations published between its inception in April 2013 and June 2017 were reviewed, alongside guidance relating to the proposed changes. Results: Six HST evaluations had been conducted by NICE and seven were in development. Five received positive reimbursement decisions with a cost per treatment/year of £125,000–£394,680. One (sebelipase alfa) was not recommended based on the prohibitively expensive cost (£491,992 per treatment/year), in the context of uncertainties around the long-term benefits. All positive recommendations have conditions attached, including a patient access scheme (eculizumab, ataluren, migalastat), managed access scheme (ataluren, elosulfase alfa), and use within expert centres (eculizumab). The proposed changes to the HST programme include implementing a cost-effectiveness threshold for ultra-ODs of £100,000–£300,000 per QALY, using a QALY weighting based on the number of additional QALYs a medicine offers. Under the proposed changes those ultra-ODs with a positive recommendation would be unlikely to significantly raise the £100,000 threshold, and therefore may not receive a positive recommendation without a patient access scheme or managed access scheme to improve costeffectiveness. Conclusions: The introduction of a cost-effectiveness threshold increases clarity about decisions regarding which ultra-ODs are routinely funded, but could make patient access more difficult as they may be less likely to be recommended by NICE. PHP246 Reviewing The Effectiveness of Uk Drug Horizon Scanning Efforts & The Production of Nice Commentary Along Therapeutic Specialties Woltmann JD National Institute for Health Research Innovation Observatory, Newcastle upon Tyne, UK
Objectives: The National Institute for Health Research Innovation Observatory is responsible for notifying the National Institute for Health & Clinical Excellence (NICE) of new drugs & indications prior to market authorisation (MA). This constitutes the first step in NICE’s topic selection, and the desired notification period is 600 days for new drugs, 450 for new indications. This research aims to explore the success of previous horizon scanning at meeting notification requirements as well as the speed at which NICE commentary was produced. Methods: All publically available NIHR horizon briefs between 2006 and Q12017 were collated and segmented by