Evaluating the administration costs of biologic drugs: development of a cost algorithm.

Biologic drugs, as with all other medical technologies, are subject to a number of regulatory, marketing, reimbursement (financing) and other demand-restricting hurdles applied by healthcare payers. One example is the routine use of cost-effectiveness analyses or health technology assessments to determine which medical technologies offer value-for-money. The manner in which these assessments are conducted suggests that, holding all else equal, the economic value of biologic drugs may be determined by how much is spent on administering these drugs or trade-offs between drug acquisition and administration costs. Yet, on the supply-side, it seems very little attention is given to how manufacturing and formulation choices affect healthcare delivery costs. This paper evaluates variations in the administration costs of biologic drugs, taking care to ensure consistent inclusion of all relevant cost resources. From this, it develops a regression-based algorithm with which manufacturers could possibly predict, during process development, how their manufacturing and formulation choices may impact on the healthcare delivery costs of their products

Economic Analysis of the Link between Advances in Biopharmaceutical Manufacturing and Healthcare Delivery Costs

Concerns about increasing expenditures on new biologic medicines has speared interests in finding solutions to contain healthcare delivery costs whilst, at least, maintaining population health indicators at the same levels. Often overlooked are investments in pharmaceutical manufacturing research, which perhaps is because manufacturing costs are thought to only make a small fraction of drug prices, and hence any impact on healthcare delivery costs is small enough to be ignored. This thesis provides evidence, to the contrary, that the impact on healthcare delivery costs cannot be trivialized. Starting with a systematic review of literature, this thesis finds that there are inconsistencies in what items are included or excluded from estimates of drug administration costs. On the back of this finding, this thesis evaluated drug administration costs for a sample of biologic drugs to identify manufacturing choices that explain most the observed variation in administration costs. It presents an algorithm pharmaceutical manufacturers could use to predict the expected administration-cost savings from reformulating biologic drug candidates still in development and/or existing medicines already on the market. This thesis goes further to argue that a primary focus on the monetary costs of drug administration ignores intangible benefits from satisfying end-user preferences for different modes of drug administration. The monetary value of these intangible benefits could be in the same order of magnitude as savings on the direct monetary costs of drug administration. In addition, this thesis shows that using cost-reducing process innovations in drug manufacturing, as opposed to cost-increasing ones, is associated with a higher number of products available for clinical use and lower prices over time; whilst the likelihood that a drug product is no longer available is seemingly unrelated to the process innovation deployed in manufacturing. The evidence put together indicate significant societal benefits from developing and implementing innovations in pharmaceutical manufacturing

Discrete-choice modelling of patient preferences for modes of drug administration.

The administration of (biologically-derived) drugs for various disease conditions involves consumption of resources that constitutes a direct monetary cost to healthcare payers and providers. An often ignored cost relates to a mismatch between patients' preferences and the mode of drug administration. The "intangible" benefits of giving patients what they want in terms of the mode of drug delivery is seldom considered. This study aims to evaluate, in monetary terms, end-user preferences for the non-monetary attributes of different modes of drug administration using a discrete-choice experiment. It provides empirical support to the notion that there are significant benefits from developing patient-friendly approaches to drug delivery. The gross benefits per patient per unit administration is in the same order of magnitude as the savings in resource costs of administering drugs. The study argues that, as long as the underlying manufacturing science is capable, a patient-centred approach to producing drug delivery systems should be encouraged and pursued

Female genital mutilation/cutting in Sierra Leone: are educated women intending to circumcise their daughters?

BACKGROUND:Female genital mutilation/cutting (FGM/C) has been recognized as a gross violation of human rights of girls and women. This is well established in numerous international legal instruments. It forms part of the initiation ceremony that confers womanhood in Sierra Leone. Girls and women who are subjected to this practice are considered to be ready for marriage by their parents and communities and are rewarded with celebrations, gifts, and public recognition. Following this, we examined the relationship between education and women's FGM/C intention for their daughters in Sierra Leone. METHODS:We used cross-sectional data from the women's file of the 2013 Sierra Leone Demographic and Health Survey (SLDHS) to explore the influence of education on FGM/C intention among women in the reproductive age (15-49). A sample of 6543 women were included in the study. Our analysis involved descriptive computation of education and FGM/C intention. This was followed by a two-level multilevel analysis. Fixed effect results were reported as Odds Ratios and Adjusted Odds Ratios with their respective credible intervals (CrIs) whilst results of the random effects were presented as variance partition coefficients and median odds ratios. RESULTS:Our findings showed that women who had no formal education were more likely to intend to circumcise their daughters [aOR = 4.3, CrI = 2.4-8.0]. Among the covariates, women aged 20-24 [aOR = 2.3, CrI = 1.5-3.4] were more likely to intend to circumcise their daughters compared to women between 45 and 49 years old. Poorest women were more likely to report intention of circumcising their daughters in the future compared with the richest [aOR = 2.1, CrI = 1.3-3.2]. We noted that, 63.3% of FGM/C intention in Sierra Leone is attributable to contextual factors. CONCLUSION:FGM/C intention is more common among women with no education, younger women as well as women in the lowest wealth category. We recommend segmented female-child educational and pro-poor policies that target uneducated women in Sierra Leone. The study further suggests that interventions to end FGM/C need to focus on broader contextual and social norms in Sierra Leone

Estimating preferences for modes of drug administration: The case of US healthcare professionals

BACKGROUND: There are hidden drug administration costs that arise from a mismatch between end-user preferences and how manufacturers choose to formulate their drug products for delivery to patients. The corollary of this is: there are "intangible benefits" from considering end-user preferences in manufacturing patient-friendly medicines. It is important then to have some idea of what pharmaceutical manufacturers should consider in making patient-friendly medicines and of the magnitude of the indirect benefits from doing so. OBJECTIVES: This study aimed to evaluate preferences of healthcare professionals in the US for the non-monetary attributes of different modes of drug administration. It uses these preference orderings to compute a monetary valuation of the indirect benefits from making patient-friendly medicines. METHODS: A survey collected choice preferences of a sample of 210 healthcare professionals in the US for two unlabelled drug options. These drugs were identical except in the levels of attributes of drug administration. Using the choice data collected, statistical models were estimated to compute gross welfare benefits, measured by the expected compensating variation, from making drugs in a more patient-friendly manner. RESULTS: The monetary value of end-user benefits from developing patient-friendly drug delivery systems is: (1) as large as the annual acquisition costs per full treatment episode for some biologic drugs; and (2) likely to fall in the "high end" of the distribution of the direct monetary costs of drug administration. CONCLUSIONS: An examination of end-user preferences should help manufacturers make more effective and efficient use of limited resources for innovations in drug delivery system, or manufacturing research in general

Modern contraceptive utilization and associated factors among married and cohabiting women in Papua New Guinea: a population-based cross-sectional study.

BackgroundUniversal access to family planning has been emphasized by the international development agenda, as evident in the Sustainable Development Goal 3.7. This notwithstanding, the use of modern contraceptives has been minimal in low- and middle-income countries, especially in Papua New Guinea. In view of this, we investigated the factors associated with the use of modern contraceptives and the associated factors among married and cohabiting women in Papua New Guinea.MethodsThe study utilised the Demographic and Health Survey data of 2345 women in sexual unions in Papua New Guinea. We employed a descriptive and binary logistic regression analyses. We presented the results as crude Odds Ratios (COR) and adjusted Odds Ratios (AOR), with 95% confidence intervals (CI) signifying level of precision. Level of statistical significance was set at p ResultsWe found that 74.4% of the women were using modern contraceptives ranging from injectables (44.5%) to other modern methods (0.23%). Women aged 15-19 [AOR = 7.425, 95% CI = 2.853, 19.32], residents of the Highland region [AOR = 1.521, 95% CI =1.086, 2.131], self-employed women in the agricultural sector [AOR = 1.710, 95% CI = 1.218, 2.400], and women who listened to radio at least once a week [AOR = 1.409, 95% CI = 1.048, 1.895] had higher odds of modern contraceptive usage. However, women in the Islands region [AOR = 0.291, 95% CI = 0.224, 0.377], women whose husbands had higher education [AOR = 0.531,95%CI = 0.318,0.886], women in professional/technical/managerial work [AOR = 0.643, 95% CI = 0.420, 0.986], and those with no child [AOR = 0.213, CI = 0.0498,0.911] had lower odds of modern contraceptive use.ConclusionOut of the 2345 participants, we found that majority of them were using modern contraceptives and the commonly used modern contraceptive was injectables. Age, region of residence, partner's education, employment, partner's desire for children, and frequency of listening to radio are associated with modern contraceptive usage. Tailored reproductive healthcare should be developed for women who are disadvantaged when it comes to the usage of modern contraceptives in order to boost modern contraceptive use among them. Further investigation is needed to unravel the motivation for the high usage of injectables among married and cohabiting women in Papua New Guinea

Barriers to accessing healthcare among women in Ghana: a multilevel modelling.

BackgroundWomen's health remains a global public health concern, as enshrined in the Sustainable Development Goals. This study, therefore, sought to assess the individual and contextual factors associated with barriers to accessing healthcare among women in Ghana.MethodsThe study was conducted among 9370 women aged 15-49, using data from the 2014 Ghana Demographic and Health Survey. Barrier to healthcare, derived from four questions- whether a woman faced problems in getting money, distance, companionship, and permission to see a doctor-was the outcome variable. Descriptive and multilevel logistic regression analyses were carried out. The fixed effect results of the multilevel logistic regression analyses were reported using adjusted odds ratios at a 95% confidence interval.ResultsMore than half (51%) of the women reported to have at least one form of barrier to accessing healthcare. Women aged 45-49 (AOR = 0.65, CI: 0.49-0.86), married women (AOR = 0.71, CI:0.58-0.87), those with a higher level of education (AOR = 0.51, CI: 0.37-0.69), those engaged in clerical or sales occupation (AOR = 0.855, CI: 0.74-0.99), and those who were covered by health insurance (AOR = 0.59, CI: 0.53-0.66) had lower odds of facing barriers in accessing healthcare. Similarly, those who listened to radio at least once in a week (AOR =0.77, CI: 0.66-0.90), those who watched television at least once a week (AOR = 0.75, CI: 0.64-0.87), and women in the richest wealth quintile (AOR = 0.47, CI: 0.35-0.63) had lower odds of facing barriers in accessing healthcare. However, women who were widowed (AOR = 1.47, CI: 1.03-2.10), those in the Volta Region (AOR 2.20, CI: I.38-3.53), and those in the Upper West Region (AOR =2.22, CI: 1.32-3.74) had the highest odds of facing barriers to healthcare accessibility.ConclusionThis study shows that individual and contextual factors are significant in predicting barriers in healthcare access in Ghana. The factors identified include age, marital status, employment, health insurance coverage, frequency of listening to radio, frequency of watching television, wealth status, and region of residence. These findings highlight the need to pay critical attention to these factors in order to achieve the Sustainable Development Goals 3.1, 3.7, and 3.8. It is equally important to strengthen existing strategies to mitigate barriers to accessing healthcare among women in Ghana

Antibody Engineering Using Phage Display with a Coiled-Coil Heterodimeric Fv Antibody Fragment

A Fab-like antibody binding unit, ccFv, in which a pair of heterodimeric coiled-coil domains was fused to VH and VL for Fv stabilization, was constructed for an anti-VEGF antibody. The anti-VEGF ccFv showed the same binding affinity as scFv but significantly improved stability and phage display level. Furthermore, phage display libraries in the ccFv format were constructed for humanization and affinity maturation of the anti-VEGF antibody. A panel of VH frameworks and VH-CDR3 variants, with a significant improvement in affinity and expressibility in both E. coli and yeast systems, was isolated from the ccFv phage libraries. These results demonstrate the potential application of the ccFv antibody format in antibody engineering

Reviewing the literature on access to prompt and effective malaria treatment in Kenya: implications for meeting the Abuja targets

<p>Abstract</p> <p>Background</p> <p>Effective case management is central to reducing malaria mortality and morbidity worldwide, but only a minority of those affected by malaria, have access to prompt effective treatment.</p> <p>In Kenya, the Division of Malaria Control is committed to ensuring that 80 percent of childhood fevers are treated with effective anti-malarial medicines within 24 hours of fever onset, but this target is largely unmet. This review aimed to document evidence on access to effective malaria treatment in Kenya, identify factors that influence access, and make recommendations on how to improve prompt access to effective malaria treatment. Since treatment-seeking patterns for malaria are similar in many settings in sub-Saharan Africa, the findings presented in this review have important lessons for other malaria endemic countries.</p> <p>Methods</p> <p>Internet searches were conducted in PUBMED (MEDLINE) and HINARI databases using specific search terms and strategies. Grey literature was obtained by soliciting reports from individual researchers working in the treatment-seeking field, from websites of major organizations involved in malaria control and from international reports.</p> <p>Results</p> <p>The review indicated that malaria treatment-seeking occurs mostly in the informal sector; that most fevers are treated, but treatment is often ineffective. Irrational drug use was identified as a problem in most studies, but determinants of this behaviour were not documented. Availability of non-recommended medicines over-the-counter and the presence of substandard anti-malarials in the market are well documented. Demand side determinants of access include perception of illness causes, severity and timing of treatment, perceptions of treatment efficacy, simplicity of regimens and ability to pay. Supply side determinants include distance to health facilities, availability of medicines, prescribing and dispensing practices and quality of medicines. Policy level factors are around the complexity and unclear messages regarding drug policy changes.</p> <p>Conclusion</p> <p>Kenya, like many other African countries, is still far from achieving the Abuja targets. The government, with support from donors, should invest adequately in mechanisms that promote access to effective treatment. Such approaches should focus on factors influencing multiple dimensions of access and will require the cooperation of all stakeholders working in malaria control.</p

No Evidence that Knops Blood Group Polymorphisms Affect Complement Receptor 1 Clustering on Erythrocytes

Clustering of Complement Receptor 1 (CR1) in the erythrocyte membrane is important for immune-complex transfer and clearance. CR1 contains the Knops blood group antigens, including the antithetical pairs Swain-Langley 1 and 2 (Sl1 and Sl2) and McCoy a and b (McCa and McCb), whose functional effects are unknown. We tested the hypothesis that the Sl and McC polymorphisms might influence CR1 clustering on erythrocyte membranes. Blood samples from 125 healthy Kenyan children were analysed by immunofluorescence and confocal microscopy to determine CR1 cluster number and volume. In agreement with previous reports, CR1 cluster number and volume were positively associated with CR1 copy number (mean number of CR1 molecules per erythrocyte). Individuals with the McCb/McCb genotype had more clusters per cell than McCa/McCa individuals. However, this association was lost when the strong effect of CR1 copy number was included in the model. No association was observed between Sl genotype, sickle cell genotype, α+thalassaemia genotype, gender or age and CR1 cluster number or volume. Therefore, after correction for CR1 copy number, the Sl and McCoy polymorphisms did not influence erythrocyte CR1 clustering, and the effects of the Knops polymorphisms on CR1 function remains unknown