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Pharmaceutical Industry\X92S Experiences With The Scientific Advice Offered By The Federal Joint Committee Within The Early Benefit Assessment Of Drugs In Germany
A450
VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6
included a pharmacoeconomic analysis, the most common type (78%) being costeffectiveness analyses. Of all 98 reports approving incorporation, 22% presented a pharmacoeconomic analysis, while 71% presented only a budget impact analysis (and 7% did not include any of them). The technology was approved for incorporation in 29% of the reports with a complete pharmacoeconomic analysis, and in 59% of those without any pharmacoeconomic analysis. Public entities accounted by 12% of the reports with a phamacoeconomic analysis and by 78% of the requests without such analysis. Conclusions: This study showed that most requests submitted to CONITEC, including those prepared by public institutions, are based on incomplete economic studies. Furthermore, the majority of such requests are approved for incorporation into the Brazilian public health system. Based on the analyzed reports, it is difficult to understand what is guiding decisions on the incorporation of new technologies in the Brazilian public healthcare system. PHP60 Pharmaceutical Industry\X92S Experiences With The Scientific Advice Offered By The Federal Joint Committee Within The Early Benefit Assessment Of Drugs In Germany Dintsios C1, Schlenkrich S2 1Heinrich Heine University of Düsseldorf, Düsseldorf, Germany, 2University of Applied Science Zittau/Görlitz, Görlitz, Germany
Objectives: The early benefit assessment of drugs was introduced in Germany in 2011. The objective was to elicit pharmaceutical manufacturers’ experiences with the scientific advices offered by the Federal Joint Committee so far. Methods: Several pharmaceutical manufacturers were interviewed on their experiences with the scientific advices offered by the federal Joint committee. Subsequently, a specifically for this purpose developed questionnaire comprising eight items on different topics and the perceived quality of the scientific advice was utilized. Results: The qualitative part comprised 7 manufacturers with 1 to 10 advices till end of 2012. With regard to the quantitative elicitation part a total of 61 completed questionnaires from 19 manufacturers were included till the beginning of 2015 (corresponding to 25% of the advices). 14 cases were about “early” advices in terms of relating to evidence before commencing phase-III trials, 44 cases concerned “late” advices (pivotal trials were just conducted or already terminated), another 2 repeated scientific advices and finally, 4 referred to miscellaneous contents (multiple answers possible). Both, the preceding qualitative and the following quantitative part of the elicitation, highlighted with regard to the process as well as to the content shortcomings from a pharmaceutical industry’s point of view: Inconsistencies, lacking expertise with conducting clinical trials, partially incomplete answers and a low readiness to engage in dialogue were criticized. On the other hand, the majority of respondents showed a positive attitude concerning unambiguousness, completeness, traceability, atmosphere and the protocol of the advice. In the course of time, propositions on study design, agreement with the determined appropriate comparative therapy and subgroup definitions improved significantly. Conclusions: A more active involvement of further stakeholders and the incorporation of procedural elements from other health care systems with longer experience, shared by the international research-based pharmaceutical industry at least, could improve the scientific advices offered by the decision maker in Germany. PHP61 Comparing The Safety Profiles Of Biosimilars With Their Originators’: A Cross Sectional Analysis On The Eu-Rmp Lepelaars LR1, Renda F2, Mantel AK1, Trotta F2 1Utrecht University, Utrecht, The Netherlands, 2Italian Medicines Agency, Rome, The Netherlands
Objectives: European legislation introduced the concept of biosimilars. It is unclear to what extent the safety profiles of biosimilars differ from those of their originators according to regulatory documents. Therefore, it is interesting to compare the safety profiles and assess planned Post Approval Safety Studies (PASSs) of biosimilars and their originators and evaluate the relevance of identified differences. Methods: A cross-sectional analysis based on regulatory documents of biosimilars with authorisation on 1 November 2015 by the European Medicines Agency (EMA) and their originators was performed. Data were obtained from publicly available websites approved by the EMA on 1 November 2015. Safety profiles were compared quantitatively and qualitatively per original safety concern. Safety concerns extracted from the Risk Management Plan (RMP) and other regulatory documents were carefully merged into general safety concerns and their clinical relevancy was classified as low, medium or high. The safety profiles of biosimilars were compared to their respective originators and the relevance of the identified differences was evaluated. Furthermore their safety profile development was assessed by extracting the safety concerns for which PASSs were planned. Results: Nineteen biosimilars and their 6 corresponding originators were included. A total of 55 general safety concerns (12 low, 21 medium and 22 highly clinically relevant) were synthesized from 113 safety concerns. For all active substances except infliximab no or only one difference was found qualitatively. The comparison of infliximab identified 3 medium clinically relevant general terms more for infliximab biosimilars and 2 general terms more for infliximab originator. PASSs were planned for 47% of the identified risks and for 44% of the uncertain risks. Conclusions: Public regulatory documents indicated that there were no highly clinically relevant differences between safety profiles for biosimilars and their originator. Furthermore PASSs were almost evenly planned for identified risks as for uncertain risks. PHP62 Assessment Of Regional Legislation Related To The Use Of Similar Biological Medicinal Products: The Italian Case Study Iorio A1, Lanati EP2 Provider Srl, Milan, Italy, 2MA Provider Srl, Milano, Italy
1MA
Objectives: To investigate the existing regional legislations related to the use of biosimilars in Italy, as a case-study of decentralised health care system. Methods: A web-based analysis was designed to collect the current legislations and then
analyze what are the recommendations about the use of biosimilars, through a checklist of items. The examined items included: (i) the definition and treatment of naïve patient, (ii) the switching from the originator product, (iii) the incentive schemes to increment biosimilar prescription, (iv) the type of tender process, (v) the monitoring system of the implemented rules and (vi) the consequences for non-compliance with regulations. Results: The collected legislation amounted to 27 documents representing the 80% of Italian Regions (17 out of 21). In 14 of these Regions (82% of the sample), the enacted rules prescribed the use of biosimilars for the treatment of naïve patients, without a clear definition of primary and secondary naïve. In 10 Regions (58% of the sample), if clinician prefer to use the originator, they are asked to provide a motivated request. A dedicated percentage of biosimilar prescription is scheduled in 9 Regions (53% of the sample). Only 5 Regions (30% of the sample) recommend to maintain the same tender process for originator and biosimilar products. The monitoring system is implemented in 11 Regions (65% of the sample) and regards drug prescriptions and the use of appropriateness indicators. 7 Regions (5 of which under repayment plan) also provide consequences against non-compliance with rules, as the revocation of health authority head or the negative performance assessment of the clinicians. Conclusions: The Italian case-study provides insights about the fragmented regional legislations. A stronger collaboration among Regions is necessary to pursue consistency on all aspects related to the use of biosimilars, also considering the upcoming introduction of more complex biosimilar antibodies. PHP63 Costs, Outcomes And Uses Of New Drugs: Drug Assessment Reports Vs Real World Data Echeverría A, Irigoyen I, Burgui C, Idoate AI, Torroba B, Idoate A, Ortega A Clínica Universidad de Navarra, Pamplona, Spain
Objectives: Estimate the deviation in drug costs, outcomes and uses in real world from expectations when new drugs are assessed for inclusion in the hospital drug formulary. Methods: We conducted a pilot retrospective observational study in a university hospital. Medical records of patients treated with new drugs with an assessment report and approved by the Pharmacy and Therapeutics Committee in 2013 were analysed. Data collected were costs, main effectiveness and safety variables, and indications. These were compared to the values of the same variables in the drug assessment reports conducted for inclusion in the hospital formulary. Percentage deviation was calculated for each drug comparing percentages, means or medians in hospital patients to those in the assessment report. Then, the median (range) of all drugs was calculated. Other collected data were therapeutic group, quality of evidence, and criteria for use. Results: We analysed 8 drugs, 50% oncologic-hematologic, used in 125 patients. Phase 3 trials were available in 80% of the cases. Forty percent of the drugs were approved in the hospital with specific criteria for use. Compliance with these criteria was observed in a median of 91% of the patients (ranging in different drugs from 0 to 100%). Half of the drugs were used off-label in at least one patient. Effectiveness was different from expected, a median of 22% lower in real world practice (range -100% to +35%). In practice, safety was worse than expected in one case. Median cost was higher than expected in 25% of the drugs. Conclusions: In this pilot study, a deviation from drug assessment reports was observed in real world regarding effectiveness, safety, uses and costs. These results need to be confirmed in a larger study. Factors related to the deviation have to be further analysed. Real world data are necessary to improve decision making. PHP64 Trend Of Antidepressant Utilization In Iran, 2006- 2015 Soleymani F1, Taheri F2 University of Medical Sciences, Tehran, Iran, 2Minitry of Health, tehran, Iran
1Tehran
Objectives: Anti-depressant medicines in general and Selective serotonin reuptake inhibitors (SSRIs) are being more frequently prescribed recently all over the world. The objective of this study is to evaluate and compare the pattern of antidepressants consumption trend in Iran and other countries as well as comparing the amount of antidepressants prescribed and used in Iran during 2006-2015. Methods: A retrospective cross-sectional study was carried out on prescription data which were obtained from the claims that pharmacies submitted to the insurers during 10 years (2006-2015). Data related to total antidepressant sales from wholesale to retail pharmacies were obtained from the official databank of national regulatory authority. Drugs were classified into four main groups according to the Anatomic Therapeutic Chemical (ATC-2012edition) System (N06AA- N06ABN06AF, N06AG- N06AX). The DDDs were calculated for these groups. The results then compared to those of European countries. Results: More than 690 million prescriptions were reviewed. The total price of prescribed antidepressant during the study period was 1942679.292 US$ while total sale was 18148288.96 US$. A total of 1,610,389,136 and 6,328,976,120 DDDs were prescribed and sold respectively during the mentioned period. An annual growth in antidepressant utilization is observed throughout the study. Conclusions: Like many Asian, European and American countries, overall consumption of antidepressant in Iran follows an increasing trend. The pattern of different antidepressants prescription varies in different countries. In Iran there is no over utilization of antidepressants observed but the significant difference between the amount of prescribed antidepressants and total sale of these medicines, suggests that antidepressants may be utilized inappropriately in Iran. Therefore besides monitoring the pattern of antidepressants use, the difference between prescription and sales amount should be considered. PHP65 Trends In Outpatient Use Of Antibiotics In Croatia Bencina G GSK, Zagreb, Croatia
Objectives: The overall volume of antibiotic consumption in the country is one of the causes of antimicrobial resistance. Croatian national data suggest that resistance
VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6
included a pharmacoeconomic analysis, the most common type (78%) being costeffectiveness analyses. Of all 98 reports approving incorporation, 22% presented a pharmacoeconomic analysis, while 71% presented only a budget impact analysis (and 7% did not include any of them). The technology was approved for incorporation in 29% of the reports with a complete pharmacoeconomic analysis, and in 59% of those without any pharmacoeconomic analysis. Public entities accounted by 12% of the reports with a phamacoeconomic analysis and by 78% of the requests without such analysis. Conclusions: This study showed that most requests submitted to CONITEC, including those prepared by public institutions, are based on incomplete economic studies. Furthermore, the majority of such requests are approved for incorporation into the Brazilian public health system. Based on the analyzed reports, it is difficult to understand what is guiding decisions on the incorporation of new technologies in the Brazilian public healthcare system. PHP60 Pharmaceutical Industry\X92S Experiences With The Scientific Advice Offered By The Federal Joint Committee Within The Early Benefit Assessment Of Drugs In Germany Dintsios C1, Schlenkrich S2 1Heinrich Heine University of Düsseldorf, Düsseldorf, Germany, 2University of Applied Science Zittau/Görlitz, Görlitz, Germany
Objectives: The early benefit assessment of drugs was introduced in Germany in 2011. The objective was to elicit pharmaceutical manufacturers’ experiences with the scientific advices offered by the Federal Joint Committee so far. Methods: Several pharmaceutical manufacturers were interviewed on their experiences with the scientific advices offered by the federal Joint committee. Subsequently, a specifically for this purpose developed questionnaire comprising eight items on different topics and the perceived quality of the scientific advice was utilized. Results: The qualitative part comprised 7 manufacturers with 1 to 10 advices till end of 2012. With regard to the quantitative elicitation part a total of 61 completed questionnaires from 19 manufacturers were included till the beginning of 2015 (corresponding to 25% of the advices). 14 cases were about “early” advices in terms of relating to evidence before commencing phase-III trials, 44 cases concerned “late” advices (pivotal trials were just conducted or already terminated), another 2 repeated scientific advices and finally, 4 referred to miscellaneous contents (multiple answers possible). Both, the preceding qualitative and the following quantitative part of the elicitation, highlighted with regard to the process as well as to the content shortcomings from a pharmaceutical industry’s point of view: Inconsistencies, lacking expertise with conducting clinical trials, partially incomplete answers and a low readiness to engage in dialogue were criticized. On the other hand, the majority of respondents showed a positive attitude concerning unambiguousness, completeness, traceability, atmosphere and the protocol of the advice. In the course of time, propositions on study design, agreement with the determined appropriate comparative therapy and subgroup definitions improved significantly. Conclusions: A more active involvement of further stakeholders and the incorporation of procedural elements from other health care systems with longer experience, shared by the international research-based pharmaceutical industry at least, could improve the scientific advices offered by the decision maker in Germany. PHP61 Comparing The Safety Profiles Of Biosimilars With Their Originators’: A Cross Sectional Analysis On The Eu-Rmp Lepelaars LR1, Renda F2, Mantel AK1, Trotta F2 1Utrecht University, Utrecht, The Netherlands, 2Italian Medicines Agency, Rome, The Netherlands
Objectives: European legislation introduced the concept of biosimilars. It is unclear to what extent the safety profiles of biosimilars differ from those of their originators according to regulatory documents. Therefore, it is interesting to compare the safety profiles and assess planned Post Approval Safety Studies (PASSs) of biosimilars and their originators and evaluate the relevance of identified differences. Methods: A cross-sectional analysis based on regulatory documents of biosimilars with authorisation on 1 November 2015 by the European Medicines Agency (EMA) and their originators was performed. Data were obtained from publicly available websites approved by the EMA on 1 November 2015. Safety profiles were compared quantitatively and qualitatively per original safety concern. Safety concerns extracted from the Risk Management Plan (RMP) and other regulatory documents were carefully merged into general safety concerns and their clinical relevancy was classified as low, medium or high. The safety profiles of biosimilars were compared to their respective originators and the relevance of the identified differences was evaluated. Furthermore their safety profile development was assessed by extracting the safety concerns for which PASSs were planned. Results: Nineteen biosimilars and their 6 corresponding originators were included. A total of 55 general safety concerns (12 low, 21 medium and 22 highly clinically relevant) were synthesized from 113 safety concerns. For all active substances except infliximab no or only one difference was found qualitatively. The comparison of infliximab identified 3 medium clinically relevant general terms more for infliximab biosimilars and 2 general terms more for infliximab originator. PASSs were planned for 47% of the identified risks and for 44% of the uncertain risks. Conclusions: Public regulatory documents indicated that there were no highly clinically relevant differences between safety profiles for biosimilars and their originator. Furthermore PASSs were almost evenly planned for identified risks as for uncertain risks. PHP62 Assessment Of Regional Legislation Related To The Use Of Similar Biological Medicinal Products: The Italian Case Study Iorio A1, Lanati EP2 Provider Srl, Milan, Italy, 2MA Provider Srl, Milano, Italy
1MA
Objectives: To investigate the existing regional legislations related to the use of biosimilars in Italy, as a case-study of decentralised health care system. Methods: A web-based analysis was designed to collect the current legislations and then
analyze what are the recommendations about the use of biosimilars, through a checklist of items. The examined items included: (i) the definition and treatment of naïve patient, (ii) the switching from the originator product, (iii) the incentive schemes to increment biosimilar prescription, (iv) the type of tender process, (v) the monitoring system of the implemented rules and (vi) the consequences for non-compliance with regulations. Results: The collected legislation amounted to 27 documents representing the 80% of Italian Regions (17 out of 21). In 14 of these Regions (82% of the sample), the enacted rules prescribed the use of biosimilars for the treatment of naïve patients, without a clear definition of primary and secondary naïve. In 10 Regions (58% of the sample), if clinician prefer to use the originator, they are asked to provide a motivated request. A dedicated percentage of biosimilar prescription is scheduled in 9 Regions (53% of the sample). Only 5 Regions (30% of the sample) recommend to maintain the same tender process for originator and biosimilar products. The monitoring system is implemented in 11 Regions (65% of the sample) and regards drug prescriptions and the use of appropriateness indicators. 7 Regions (5 of which under repayment plan) also provide consequences against non-compliance with rules, as the revocation of health authority head or the negative performance assessment of the clinicians. Conclusions: The Italian case-study provides insights about the fragmented regional legislations. A stronger collaboration among Regions is necessary to pursue consistency on all aspects related to the use of biosimilars, also considering the upcoming introduction of more complex biosimilar antibodies. PHP63 Costs, Outcomes And Uses Of New Drugs: Drug Assessment Reports Vs Real World Data Echeverría A, Irigoyen I, Burgui C, Idoate AI, Torroba B, Idoate A, Ortega A Clínica Universidad de Navarra, Pamplona, Spain
Objectives: Estimate the deviation in drug costs, outcomes and uses in real world from expectations when new drugs are assessed for inclusion in the hospital drug formulary. Methods: We conducted a pilot retrospective observational study in a university hospital. Medical records of patients treated with new drugs with an assessment report and approved by the Pharmacy and Therapeutics Committee in 2013 were analysed. Data collected were costs, main effectiveness and safety variables, and indications. These were compared to the values of the same variables in the drug assessment reports conducted for inclusion in the hospital formulary. Percentage deviation was calculated for each drug comparing percentages, means or medians in hospital patients to those in the assessment report. Then, the median (range) of all drugs was calculated. Other collected data were therapeutic group, quality of evidence, and criteria for use. Results: We analysed 8 drugs, 50% oncologic-hematologic, used in 125 patients. Phase 3 trials were available in 80% of the cases. Forty percent of the drugs were approved in the hospital with specific criteria for use. Compliance with these criteria was observed in a median of 91% of the patients (ranging in different drugs from 0 to 100%). Half of the drugs were used off-label in at least one patient. Effectiveness was different from expected, a median of 22% lower in real world practice (range -100% to +35%). In practice, safety was worse than expected in one case. Median cost was higher than expected in 25% of the drugs. Conclusions: In this pilot study, a deviation from drug assessment reports was observed in real world regarding effectiveness, safety, uses and costs. These results need to be confirmed in a larger study. Factors related to the deviation have to be further analysed. Real world data are necessary to improve decision making. PHP64 Trend Of Antidepressant Utilization In Iran, 2006- 2015 Soleymani F1, Taheri F2 University of Medical Sciences, Tehran, Iran, 2Minitry of Health, tehran, Iran
1Tehran
Objectives: Anti-depressant medicines in general and Selective serotonin reuptake inhibitors (SSRIs) are being more frequently prescribed recently all over the world. The objective of this study is to evaluate and compare the pattern of antidepressants consumption trend in Iran and other countries as well as comparing the amount of antidepressants prescribed and used in Iran during 2006-2015. Methods: A retrospective cross-sectional study was carried out on prescription data which were obtained from the claims that pharmacies submitted to the insurers during 10 years (2006-2015). Data related to total antidepressant sales from wholesale to retail pharmacies were obtained from the official databank of national regulatory authority. Drugs were classified into four main groups according to the Anatomic Therapeutic Chemical (ATC-2012edition) System (N06AA- N06ABN06AF, N06AG- N06AX). The DDDs were calculated for these groups. The results then compared to those of European countries. Results: More than 690 million prescriptions were reviewed. The total price of prescribed antidepressant during the study period was 1942679.292 US$ while total sale was 18148288.96 US$. A total of 1,610,389,136 and 6,328,976,120 DDDs were prescribed and sold respectively during the mentioned period. An annual growth in antidepressant utilization is observed throughout the study. Conclusions: Like many Asian, European and American countries, overall consumption of antidepressant in Iran follows an increasing trend. The pattern of different antidepressants prescription varies in different countries. In Iran there is no over utilization of antidepressants observed but the significant difference between the amount of prescribed antidepressants and total sale of these medicines, suggests that antidepressants may be utilized inappropriately in Iran. Therefore besides monitoring the pattern of antidepressants use, the difference between prescription and sales amount should be considered. PHP65 Trends In Outpatient Use Of Antibiotics In Croatia Bencina G GSK, Zagreb, Croatia
Objectives: The overall volume of antibiotic consumption in the country is one of the causes of antimicrobial resistance. Croatian national data suggest that resistance