The Changing Nature of Pharmaceutical R&D - Opportunities for Asia?

During the 1990''s, the pharmaceutical R&D process has witnessed tremendous technological changes. The emergence of new tools like ''combinatorial chemistry'', ''high throughput screening'' and the in-creasing use of computer-aided in silico experiments has led to significant improvements of research efficiency. This paper discusses the economic impact of this trend. It is argued that the resulting radical improvements in R&D productivity have lowered the minimum efficient scale in pharmeceutical research. As a consequence, the main bottleneck in pharmaceutical research has shifted from the mechanical act of synthesising and screening a sufficient number of active compounds to scientific excellence. Empirical finding indicate that the latter can more easily be achieved in smaller, highly focused firms. Accordingly, the most efficient way to currently conduct pharmaceutical R&D may be a new ''division of labour'' in research between small, highly specialised firms conducting research and large firms focusing on the development, testing, and marketing or new drugs. This reopens a ''window of opportunity'' for Asian pharmaceutical firms who had lost out in the previous race to ever increasing size.economics of technology ;

The Determinants of Pharmaceutical R&D Expenditures: Evidence from Japan

During the past 20 years, the world pharmaceutical industry has experienced a dramatic increase in R&D intensity. We apply and extend a model developed by Grabowski and Vernon (2000) with a pooled data sample of the 15 publicly listed Japanese drug firms for the period 1987 to 1998. As in the reference paper, we find expected returns to be an important determinant of R&D spending in the Japanese drug industry, albeit considerably smaller than in the U.S., which is particularly obvious in the case of returns from newly introduced drugs. However, our results are sensitive to econometric model specification, in particular to controlling for serial correlation and to a dynamic specification of the baseline model. Likewise, estimates on financial constraints are sensitive to model specification, indicating that Japanese drug firms face small or no financial constraints. Our results are consistent with the general literature on R&D investment behaviour, yet raise some methodological questions with regard to the original study.R&D, investment, panel data estimation, pharmaceuticals, Japan

Pharmaceutical regulation in Europe and its impact on corporate R&D

Objectives: Many European countries regulate the markets for prescription drugs in order to cope with rising health expenditures. On the other hand, regulation distorts incentives to invest in pharmaceutical R&D. This study aims at empirically assessing the impact of regulation on pharmaceutical R&D expenditures. Methods: We analyze a sample of 20 leading pharmaceutical companies between 2000 and 2008. The share of sales in Europe serves as a proxy for the degree of pharmaceutical regulation. We control for other firm specific determinants of R&D such as cash flow, company size, leverage ratio, growth rate, and Tobin's q. Results: Our results suggest a nonlinear relationship between European sales ratio and R&D intensity. Beyond a threshold of 33% of sales generated in Europe, a higher presence in Europe is associated with lower R&D investments. Conclusion: The results can be interpreted as further evidence of the deteriorating effect of regulation on firm's incentives to invest in R&D

Treatment strategies for treatment naive HIV patients in Germany: evidence from claims data

A recent observational study of HIV patients in Germany suggests that treatment naive patients that are in a more advanced stage of their disease are more likely to receive a treatment regimen based on a boosted protease inhibitor (PI/r) compared with a non-nucleoside reverse-transcriptase-inhibitor (NNRTI) base regimen. To validate those results we analysed claims data of seven German sickness funds from 2009 to 2012 with approximately 4 million beneficiaries. Patients in a more advanced disease state (CDC class C) had a higher likelihood to receive a PI/r based regime rather than a NNRTI based regimen as their initial treatment. There was also a significant correlation between PI/r based regimen and number of comorbidities but not with age. Our results confirm a highly significant relationship between being in a more severe stage of HIV disease and a PI/r based treatment regimen

Vergleichbarkeit internationaler Arzneimittelpreise: Internationale Preisreferenzierung in Deutschland durch das AMNOG

Diese Studie zeigt, dass die Maximierung der sozialen Wohlfahrt, also die Verfügbarkeit von innovativen und günstigen Produkten in Europa, durch eine Korrektur der tatsächlichen Abgabepreise in anderen Ländern gemäß der wirtschaftlichen Leistungsfähigkeit [und nicht nur des Preisniveaus] erreicht werden kann. Die im Rahmen des AMNOG vorgesehene europäische Preisreferenzierung für innovative Arzneimittel in Deutschland macht durch eine Gewichtung mit dem BIP pro Kopf eine wohlfahrtsoptimale europäische Preisgestaltung möglich. Ergebnisse einer Berechnung am Beispiel des Onkologikums Zytiga® [Abirateronacetat] zeigen, dass europäische Arzneimittelpreisdifferenzen von bis zu 38% möglich sind, ohne den Referenzpreis in Deutschland unter ein sozial optimales Niveau zu senken

Treatment strategies for treatment naive HIV patients in Germany: evidence from claims data

A recent observational study of HIV patients in Germany suggests that treatment naive patients that are in a more advanced stage of their disease are more likely to receive a treatment regimen based on a boosted protease inhibitor (PI/r) compared with a non-nucleoside reverse-transcriptase-inhibitor (NNRTI) base regimen. To validate those results we analysed claims data of seven German sickness funds from 2009 to 2012 with approximately 4 million beneficiaries. Patients in a more advanced disease state (CDC class C) had a higher likelihood to receive a PI/r based regime rather than a NNRTI based regimen as their initial treatment. There was also a significant correlation between PI/r based regimen and number of comorbidities but not with age. Our results confirm a highly significant relationship between being in a more severe stage of HIV disease and a PI/r based treatment regimen

Cost-effectiveness of Interferon-free therapy for Hepatitis C in Germany - an application of the efficiency frontier approach

Background:The approval of direct-acting antivirals for Interferon-free treatment revolutionized the therapy of chronic Hepatitis C infection. As of August 2014, two treatment regimens for genotype 1 infection received conditional approval in the European Union: Sofosbuvir and Ribavirin for 24 weeks and Sofosbuvir and Simeprevir with or without Ribavirin for 12 weeks. We aim to analyze the cost-effectiveness of both regimens in Germany. Methods: We set up a Markov model with a lifetime horizon to simulate immediate treatment success and long-term disease progression for treatment-naive patients. The model analyzes both short-term and long-term costs and benefits from the perspective of the German Statutory Health Insurance. We apply the efficiency frontier method, which was suggested by German Institute for Quality and Efficiency in Health Care for cost-effectiveness analysis in Germany. Results: The efficiency frontier is defined by dual therapy and first generation direct-acting antiviral Boceprevir, yielding a maximum of € 1,447.69 per additional percentage point of sustained virologic response gained. Even without rebates, Sofosbuvir/Simeprevir is very close with € 1,560.13 per additional percentage point. It is both more effective and less expensive than Sofosbuvir/Ribavirin. Conclusions: In addition to higher sustained virologic response rates, new direct-acting antivirals save long-term costs by preventing complications such as liver cirrhosis, hepatocellular carcinoma and ultimately liver transplants, thereby offsetting part of higher drug costs. Our findings are in line with the guidance published by German Society for Gastroenterology, Digestive and Metabolic Diseases, which recommends Sofosbuvir/Simeprevir for Interferon ineligible or intolerant patients

Estimation of Health-State Utility Values and Factors Driving Health-Related Quality of Life in People Living with HIV and AIDS and Receiving cART in Germany: Baseline Analysis of a Cohort Study

HIV has become a chronic disease since widespread of combined antiretroviral therapy (cART). Understanding the influence of therapeutic and preventive interventions on health-related quality of life (HRQoL) of people living with HIV and AIDS (PLWHA) is important. Information about health state utilities and HRQoL in PLWHA after the introduction of cART is limited, especially in Germany. The study aims to estimate and describe health state utilities and HRQoL in PLWHA in Germany and explore the effects of patient characteristics, clinical and treatment factors. Utilities and HRQoL in PLWHA in Germany were measured with the generic EQ-5D-3L questionnaire. Health state utilities were calculated based on the EQ-5D descriptive system using the German EQ-5D-3L time trade-off (TTO) value set. HRQoL was calculated based on the EQ visual analogue scale (EQ-VAS). Extensive descriptive analyses were performed to represent utility values for different groups of the patients. Generalized linear models (GLMs) with beta-inflated distributions were used to determine patient characteristics and clinical factors that influence TTO utilities and VAS scores. 1056 PLWHA completed the EQ-5D-3L questionnaires at the beginning of the study. The mean TTO utility value is 0.912 (SD ± 0.154), and the mean VAS HRQoL is 84.32 (SD ± 18.55). “Anxiety/depression” and “pain/physical discomfort” are the most affected dimensions. A longer period of living with HIV, a lower CD4-cell count, having symptomatic HIV or AIDS and an increased number of changes in therapy are associated with decreased utilities and a lower probability of having HRQoL of perfect health. No significant effect of duration of regimen was found. Depression significantly decreases TTO utility values. Higher education, full-time employment and female gender are associated with higher utilities. The resulted EQ-VAS values for PLWHA in Germany are comparable with EQ-VAS estimates for the general population. The obtained estimates can be used as inputs for health economic evaluations of HIV-interventions. Addressing anxiety and depression may reduce the quality of life impairment in PLWHA. Impact of comorbidities needs further investigation. © 2021, The Author(s)

a meta-analysis and historical comparison

Background About one third of patients infected with human immunodeficiency virus (HIV) also have chronic hepatitis due to hepatitis C virus (HCV). HCV therapy with simeprevir, pegylated interferon alfa (PegIFNα) and ribavirin (RBV) have been shown to be superior to PegIFNα + RBV alone in non-HIV patients, but no randomized trials in patients with HCV genotype 1 (HCV-1) / HIV coinfection are available. Methods This was a historical comparison of study C212 (simeprevir + PegIFNα-2a + RBV in patients with HCV-1/HIV coinfection) with studies in which HCV-1/HIV coinfected patients were treated with PegIFNα-2a + RBV alone. A systematic literature search was performed to identify eligible studies. Efficacy and safety results of PegIFNα-2a + RBV studies were combined in random- and fixed-effects inverse-variance weighted meta-analyses of proportions using the Freeman-Tukey double arcsin transformation method, and compared with the results of study C212. Results The literature search revealed a total of 2392 records, with 206 articles selected for full-text review. Finally, 11 relevant articles reporting on 12 relevant study groups were included. Results on sustained virologic response 24 weeks after end of treatment (SVR24) were available from all 12 study groups. Pooled SVR24 for PegIFNα-2a + RBV from the random-effects meta- analysis was 28.2 % (95 % CI 23.8 % to 32.9 %). The comparison between study C212 (SVR24 = 72.6 %; 95 % CI 63.1 % to 80.9 %) revealed substantial superiority of simeprevir + PegIFNα-2a + RBV compared to PegIFNα-2a + RBV alone, with an absolute risk difference of 45 % (95 % CI 34 to 55). This finding was robust in a sensitivity analysis that only included historical studies with a planned treatment duration of at least 48 weeks and the same RBV dose as in study C212. No increases in the frequency of important adverse event categories including anemia were identified, but these analyses were limited by the low number of studies. Conclusion This historical comparison provides first systematic evidence for the superiority of simeprevir + PegIFNα-2a + RBV compared to PegIFNα-2a + RBV in patients with HCV-1 / HIV coinfection. Given the limitations of the historical comparison for safety endpoints, additional data on the comparative safety of simeprevir in patients with HCV-1 / HIV coinfection would be desirable. Trial registration Identifier for study TMC435-TiDP16-C212 (ClinicalTrials.gov): NCT01479868