The impact of pharmaceutical innovation on longevity and medical expenditure in France, 2000–2009

Longitudinal, disease-level data are used to analyze the impact of pharmaceutical innovation on longevity (mean age at death) and medical expenditure in France during the period 2000–2009. The estimates imply that pharmaceutical innovation increased mean age at death by 0.29 years (3.43 months) during this period—about one-fifth of the total increase in longevity. This estimate is smaller than those obtained in previous studies of Germany and the U.S., but the rate of adoption of new drugs was lower in France. Longevity is much more strongly related to the number of drugs than it is to the number of drug classes.Pharmaceutical innovation during 2000–2009 is estimated to have increased per capita pharmaceutical expenditure by $125 (26%) in 2009, but most (87%) of this increase was offset by a reduction in hospital expenditure. The baseline estimate of the cost per life-year gained from pharmaceutical innovation in France during 2000–2009 is about $8100. This estimate is fairly close to the mean of estimates obtained ($10,800) from U.S., German, and Australian studies.     

我国创新药研发模式与价值评估(I)

创新药研发对企业研发能力要求高,目前我国大部分药企仍然处于仿创阶段,但随着政策环境的改善,国家不断释放鼓励创新信号, 创新型药企不断涌现,传统药企积极布局,创新药物迎来发展机遇。借鉴国外创新药研发经验,探讨我国创新药的 3 种研发模式及估值方法, 解析创新药研发的机遇与风险。     

·我国创新药研发模式与价值评估(II)

创新药研发对企业研发能力要求高,目前我国大部分药企仍然处于仿创阶段,但随着政策环境的改善,国家不断释放鼓励创新信号, 临前所未有的挑战,呼唤历史发展的转折点。 3.1 由仿到创的大型创新药企——1.0模式 2015 年临床数据自查、仿制药一致性评价、化学药 国内当下的政策环境和市场环境,使得我国创新 品注册分类改革工作方案、上市许可人制度试点、药监市 朱迅 创新型药企不断涌现,传统药企积极布局,创新药物迎来发展机遇。借鉴国外创新药研发经验,探讨我国创新药的 3 种研发模式及估值方法, 解析创新药研发的机遇与风险。     

International variability of ages at menarche and menopause: patterns and main determinants.

The purpose of this study was to review published studies on the variability of age at menarche and age at menopause throughout the world, and to identify the main causes for age variation in the timing of these events. We first present a summary table including mean (or median) values of the age at menarche in 67 countries, and of the age at menopause in 26 countries. General linear models showed that mean age at menarche was strongly linked to the mean female life expectancy, suggesting that one or several variables responsible for inequalities in longevity similarly influenced the onset of menarche. A closer examination of the data revealed that among several variables reflecting living conditions, the factors best explaining the variation in age at menarche were adult illiteracy rate and vegetable calorie consumption. Because adult illiteracy rate has some correlation with the age at which children are involved in physical activities that can be detrimental in terms of energy expenditure, our results suggest that age at menarche reflects more a trend in energy balance than merely nutritional status. In addition, we found the main determinant of age at menopause to be the mean fertility. This study thus suggests that, on a large scale, age at menarche is mainly determined by extrinsic factors such as living conditions, while age at menopause seems to be mainly influenced by intrinsic factors such as the reproductive history of individuals. Finally, these findings suggest that human patterns cannot be addressed solely by traditional, small-scale investigations on single populations. Rather, complementary research on a larger scale, such as this study, may be more appropriate in defining some interesting applications to the practical problems of human ecology.     

A divergent pattern of the sex difference in life expectancy: Sweden and Japan, early 1970s-late 1990s

For most of the 20th century the sex gap in life expectancy in the industrialized countries has widened in favor of women. By the early 1980s a reversal in the long-term pattern of this differential had occurred in some countries, where it reached a maximum and thereafter followed a declining trend. Of particular interest to the present investigation is the anomalous experience of Japan, where unlike other high-income countries the female advantage in life expectancy has been expanding. We contrast the case of Japan with that of Sweden, where, like many other high-income nations, the sex differential in longevity has been narrowing in recent years. We observe that in Sweden, until the early 1980s, the sex gap in life expectancy (female-male) exceeded that of Japan; but this situation reversed in subsequent periods, when the Swedish differential narrowed and that of Japan widened. A decomposition analysis indicates that these divergent patterns since 1980 have resulted mainly from larger than expected reductions in male mortality in Sweden due to heart disease and from accidents and violence, lung cancer and "other" cancers. In Japan, death rates for men and women from heart disease--which is a leading cause of death--have tended to decline more or less at the same pace since the early 1980s; and with regard to lung cancer, and "other" neoplasms, male death rates in Japan have been rising while those of women have either declined or risen more slowly. Moreover, during the 1990s, male and female suicide rates rose in Japan, but the rates for men went up faster. Altogether, the net effect of these divergent mortality trends for men and women in Japan underlie much of the observed widening of its sex differential in longevity in recent years.     

Drug related deaths in the Split-Dalmatia County 1997-2007

Drug overdoses are a major cause of mortality for drug users and, in many countries, are the leading cause of death in this group. The aim of the present study is to explore the frequency of all drug related deaths in the Split-Dalmatia County in the period between 1997 and 2007 and to analyze some of the characteristics of these deaths to help target preventive policies. The data on drug related deaths were collected using records from the Department of Forensic Medicine, Clinical Hospital Centre Split, University of Split, School of Medicine. There were 190 drug related deaths in the observed period of 11 years. Statistically significant difference (p = 0.004, chi2-test for trend) was found in the number of deaths in 1997 in comparison with the number of deaths in 2007. The majority of 105 (55%) the decedents were 25-34 years old, and 92.1% (175) of them were male. There was a 94% higher probability of mortality in the 25-34 years group (chi2 = 5.55, p = 0.064). Average age of all dead people was 31.01 +/- 7.59 years (median 31.0 years; range 18-49). Almost three quarters of the decedents were single and more than three fifths hadn't been employed. The most common location of death was at home. Approximately, 80% were autopsied followed by full histological and toxicological analyses. Out of all examined cases, the majority of drug related deaths (93 or 60.8%) were attributed to heroin. Heroin was the sole cause of death in 35 (22.9%) cases. Methadone was cause of death in 24 (15.7%) cases. 3.4-methylenedioxy-methamphetamine (MDMA) deaths were rare (3.3%). Cocaine deaths were also rare (1.3%). Three fifths (55.6%) of the cases involved includes multi-substance use. During the investigation there was an evident trend towards multi-substance abuse patterns. These data suggest that interventions to prevent drug related mortality should address the use of drugs such as heroin and alcohol in combination.     

Is the United States Still Dominant in the Global Pharmaceutical Innovation Network?

The dramatic growth of research and development activities in the pharmaceutical sector in emerging economies raises the question of whether the United States still keeps its dominant role in the global pharmaceutical innovation landscape. This paper focuses on investigating the role of the United States in global pharmaceutical innovation, and differs from previous studies by shifting attention to a network analytic perspective to track the global distribution of pharmaceutical inventions. Our sample is composed of key patents covering all new drugs approved by the Food and Drug Administration between 1996 and 2010. The results show that the United States still dominates in the global pharmaceutical innovation network, especially when it comes to essential core inventions. However, the United States shows a slightly decreasing prominence in the networks of either total new drugs or New Molecular Entity (NME) drugs in the time period 2006–2010 as compared to previous time periods, revealed by subtle traces of network centralities.     

Risk behaviours for HIV infection among drug users in prison.

OBJECTIVE--To study a group of injecting drug users to establish the degree of illicit drug use in prisons, the prevalence of risk behaviours for HIV infection, and the uptake of treatment for drug dependency with drugs within the prison system. DESIGN--Anonymous, self administered, questionnaire. SETTING--Two drug agencies in central London; one operating a scheme for exchanging needles, and the other offering drug advice and information. SUBJECTS--50 (42 Men, eight women) self selected injecting drug users (mean age 31.2 (range 21-42)), all of whom had been held in custody at some time since 1982. MAIN OUTCOME MEASURES--Details about periods served in custody since 1982; the number of respondents who took drugs (orally or by injection), either illicitly or prescribed, while in prison and the types of substances taken; the respondents'' sexual activity in prison and between periods in custody. RESULTS--The average time spent in custody before the study was 20.6 months (range 1-72). Most prosecutions were directly or indirectly related to drug taking. 47 Of the 50 respondents reported taking at least one illicit drug while in custody; 33 by injection, 26 of whom had shared injecting equipment. 30 Had been treated for drug dependency by the prescribing of drugs while in prison. While in custody, one woman and four men (with a mean of seven (range 2-16) male partners) had had sex. Between periods spent in custody, men reported having a mean of eight (range 0-90) female partners and women a mean of one (range 0-3) male partner. Three men had had sex with other men, with a mean of six (range 2-11) partners. Since their last period in custody, men had had a mean of two (range 0-18) female partners and women had had a mean of two (range 1-3) male partners. Five men had also had male partners. CONCLUSIONS--A high prevalence of injecting and sexual risk behaviours among injecting drug users within and between periods in custody has been shown. Most of these offenders continued to take drugs while in custody, and just over half not only injected drugs but shared equipment. Some of the male prisoners compounded their risk of HIV infection by engaging in sexual activity with multiple partners. Prisoners who then have multiple sexual partners after release place their partners in the community at particular risk of HIV infection. Although many of the drug users were prescribed drugs for their dependency, limited access to appropriate treatment, counselling, and health education may compound the situation.     

Evidence of sex-linked effects on the inheritance of human longevity: a population-based study in the Valserine valley (French Jura), 18-20th centuries

A long-standing puzzle in gerontology is the sex dependence of human longevity and its inheritance. We have analysed the sex-linked pattern of inheritance of longevity from 643 nuclear families on the historical population register of a French valley. We have focused on mean conditional life expectancy at a minimum age of 50 years, thus, in the present study, longevity refers to late or post-reproductive survival. A comparison of parents' and offspring's longevity has shown the existence of a heritable component of late survival in this population. We have found that the heritable component was substantially larger for daughters compared to sons. Moreover, this result appeared to be specific to late survival, that is, when only post-reproductive mortality for parental and offspring generations is taken into account. The stronger resemblance of parents to their daughters was no longer observed when considering younger ages at death for the offspring. This observation explains the hitherto unaccountable diversity of data in previous studies.     

Raising the Barriers to Access to Medicines in the Developing World – The Relentless Push for Data Exclusivity

Since the adoption of the WTO‐TRIPS Agreement in 1994, there has been significant controversy over the impact of pharmaceutical patent protection on the access to medicines in the developing world. In addition to the market exclusivity provided by patents, the pharmaceutical industry has also sought to further extend their monopolies by advocating the need for additional ‘regulatory’ protection for new medicines, known as data exclusivity. Data exclusivity limits the use of clinical trial data that need to be submitted to the regulatory authorities before a new drug can enter the market. For a specified period, generic competitors cannot apply for regulatory approval for equivalent drugs relying on the originator's data. As a consequence, data exclusivity lengthens the monopoly for the original drug, impairing the availability of generic drugs. This article illustrates how the pharmaceutical industry has convinced the US and the EU to impose data exclusivity on their trade partners, many of them developing countries. The key arguments formulated by the pharmaceutical industry in favor of adopting data exclusivity and their underlying ethical assumptions are described in this article, analyzed, and found to be unconvincing. Contrary to industry's arguments, it is unlikely that data exclusivity will promote innovation, especially in developing countries. Moreover, the industry's appeal to a property rights claim over clinical test data and the idea that data exclusivity can prevent the generic competitors from ‘free‐riding’ encounters some important problems: Neither legitimize excluding all others.     

Relationship of income and childlessness

ABSTRACT

We investigated the impact of diabetes on US life expectancy by sex and race/ethnicity using a prospective cohort study design. Cohorts were drawn from 1997 to 2009 waves of the National Health Interview Survey and linked to death records through December 31, 2011. We combined data on the prevalence of diabetes among decedents with estimates of the hazard ratios of individuals diagnosed with diabetes to calculate population attributable fractions (PAFs) by age, sex, and race/ethnicity at ages 30 and above. These estimates were then applied to deaths in the official US life table for 2010 to estimate effects of diabetes on life expectancy.

Diabetes was responsible for a reduction of 0.83 years of life expectancy for men at age 30 and 0.89 years for 30-year-old women. The impact was greatest among Black women at 1.05 years. Estimates based on traditional demographic and actuarial methods using the frequency with which a disease appears as an underlying cause of death on death certificates produced a reduction in life expectancy at age 30 of only 0.33 years.

We conclude that diabetes is substantially reducing US longevity and that its effect is seriously underestimated when using data on underlying causes of death.     

Immunocontraception and increased longevity in equids

Intensive population management by means of fertility control has been shown to change the age profile of a wild horse herd. The primary change has been an increase in the number and percent of older animals, as expected, but also the appearance of new and older age classes. An examination of direct effects of fertility control on two groups of treated animals shows a significant increase in longevity over non‐treated animals that is associated with contraceptive treatment. The mean age at death (MAD) was calculated for 128 wild horses for which precise birth and death dates were known, including 56 stallions, 42 untreated mares, 11 mares treated with a porcine zona pellucida contraceptive vaccine for 1–2 years, and 19 mares treated with the same vaccine for ≥3 years. The MAD for stallions (10.3±0.84 [SEM] years), and mares treated for 1–2 years (10.2±0.56), was significantly greater (P<0.05) than for untreated mares (6.4±0.85), and significantly <19.9±1.66 for mares treated ≥3 years (19.9±1.66). Zoo Biol 26:237–244, 2007. © 2006 Wiley‐Liss, Inc.     

Histone deacetylase inhibitors—turning epigenic mechanisms of gene regulation into tools of therapeutic intervention in malignant and other diseases

Histone deacetylase inhibitors reside among the most promising targeted anticancer agents that are potent inducers of growth arrest, differentiation, and/or apoptotic cell death of transformed cells. In October 2006, the US Food and Drug Administration approved the first drug of this new class, vorinostat (1, Zolinza, Merck). Several histone deacetylase (HDAC) inhibitors more are in clinical trials. HDAC inhibitors have shown significant activity against a variety of hematological and solid tumors at doses that are well tolerated by patients, both in monotherapy as well as in combination therapy with other drugs. This paper reviews the most recent developments in HDAC inhibitor design, particularly in the context of anticancer therapy, and other possible pharmaceutical applications.     

Patents Associated with High-Cost Drugs in Australia

Australia, like most countries, faces high and rapidly-rising drug costs. There are longstanding concerns about pharmaceutical companies inappropriately extending their monopoly position by “evergreening” blockbuster drugs, through misuse of the patent system. There is, however, very little empirical information about this behaviour. We fill the gap by analysing all of the patents associated with 15 of the costliest drugs in Australia over the last 20 years. Specifically, we search the patent register to identify all the granted patents that cover the active pharmaceutical ingredient of the high-cost drugs. Then, we classify the patents by type, and identify their owners. We find a mean of 49 patents associated with each drug. Three-quarters of these patents are owned by companies other than the drug''s originator. Surprisingly, the majority of all patents are owned by companies that do not have a record of developing top-selling drugs. Our findings show that a multitude of players seek monopoly control over innovations to blockbuster drugs. Consequently, attempts to control drug costs by mitigating misuse of the patent system are likely to miss the mark if they focus only on the patenting activities of originators.     

基于文献计量学分析的免疫性疾病领域药学研究进展

免疫性疾病是全球发病率和死亡率最高的疾病之一,近年来呈上升趋势。免疫性疾病领域药学研究的快速发展推动了治疗免疫性疾 病的药物的研发和上市。采用文献计量的方法从研发趋势、国家分布、机构分布、研究热点等多个角度对全球免疫性疾病领域药学研究的 情况进行分析,为我国治疗免疫性疾病的药物研发和相关政策制定提供参考。     

Allocation of accumulated resources among close kin: Inheritance in Sacramento,California, 1890–1984

We analyze the legacies of 1538 testate decedents from Sacramento, California 1890–1984. Spouse and/or children received an average 92% of the state. The few women who were survived by a spouse more often excluded their husbands in favor of their children than did husbands exclude wives. We explain this difference in spousal treatment in terms of the reproductive potential of the two sexes at the average age of death. Fathers and mothers without spouses bequeathed the majority of assets to children. Seventy-one percent of parents with two or more children treated them absolutely equally. Sex ratio among offspring was equal. There was no evidence of a general sex preference or a wealth by sex-preference interaction. Decedents with two or more daughters treated them more equitably than did decedents with two or more sons— additional evidence that treatment of daughters is less subject to environmental and individual variation than is the treatment of sons. Decedents without biological children treated adopted children like biological children. Smaller legacies to the few adopted children in families with biological children can be explained by increased sibship size.     

Association between healthy life expectancy at birth and consanguineous marriages in 63 countries

In order to investigate the association between mean inbreeding coefficient (α) and healthy life expectancy at birth (HALE; years) the present ecological study on 63 countries was done. Statistical analysis showed that HALE negatively and positively correlated with log(10)α and log(10)GNI per capita, respectively (p<0.001). It should be noted that log(10)α and log(10)GNI per capita were significantly correlated with each other (p<0.001). After controlling for log(10)GNI per capita, significant negative correlations between log(10)α and HALE were observed. The countries were stratified according to their GNI per capita into low- and high-income countries. In countries with high income, after controlling for log(10)GNI per capita, the correlation between HALE at birth and log(10)α was significant (for males r=-0.399, df=32, p=0.001; for females r=-0.683, df=32, p<0.001). In high-income Asian and African countries, where consanguineous marriage is common, after controlling for log(10)GNI per capita, the correlation between HALE at birth and log(10)α was significant (for males r=-0.819, df=8, p=0.004; for females r=-0.936, df=8, p<0.001). It seems that consanguinity influences HALE independent of country income.     

Evolution of senescence: Natural increase of populations displaying gompertz- or power-law death rates and constant or age-dependent maternity rates

Several hypothetical populations which differ in degrees of senescence are compared with respect to their rates of natural increase. The rate of natural increase is employed as a measure of selective advantage. The populations are characterized by their maternity and death rates, expressed as functions of age. Maternity rates are described by constant or quasi-human, age-dependent functions. Death rates are described by constant, Gompertzian (exponential) or power functions. Longevity functions, representing the probability of survival to a specific age, are obtained by integrating the death rate functions. The degree of senescence of a population is measured by the rapidity of ascent of its death-rate function or by the rectangularity of its longevity function. The increase in death rate late in life which constitutes senescence is compensated by a decrease in death rate early in life. The balance between the two changes in rate is, by assumption, such that the mean value of the longevity function is independent of the degree of senescence. This assumption makes it possible to separate the effects produced by the evolution of senescence from those caused by changes in longevity.The rate of natural increase is obtained by numerical solution of an integral characteristic equation. The results show that senescence is advantageous in all populations except those in which the maternity function is constant and the size is declining at a rapid rate. When the parameters entering into the longevity functions have values such that the functions approximate human longevity data, the improvement in the rate of natural increase resulting from senescence closely approaches limiting values obtained with the use of a precisely rectangular longevity function. Other results support the observation that reproduction at an early age confers greater selective advantage than equivalent reproduction later in life.     

The effects of pond duration on the life history traits of an ephemeral pond crustacean,Eulimnadia texana

We examined the relationship between pond duration and life history characters of the clam shrimp Eulimnadia texana, a species inhabiting ephemeral ponds in southwestern North America. Since the shrimp live in temporary habitats, we predicted that there should be high selection pressure on life history characteristics associated with rapid development (e.g., fast growth, early maturity, etc.), rather than selection for increased longevity. Pond duration was estimated using a combination of average monthly rainfall and pond size (surface to volume ratio). Shrimp that live in smaller ponds (high surface to volume ratio)in areas with low average rainfall should, on average, experience a shorter total time available for development than those in larger ponds or in areas of higher rainfall. These shrimp should have an earlier age at maturity, reduced longevity, lower fecundity, and faster growth. Five replicate populations of clam shrimp were collected as cysts from five ponds. These shrimp were raised in a common garden experiment in the laboratory. Daily measurements of growth and egg production were taken and ages at maturity and death were recorded. Shrimp from areas with higher average rainfall had slower growth, higher fecundity, greater longevity, and an earlier age at maturity than those from areas with lower average rainfall. If average rainfall is an accurate measure of pond duration, then the first three of these life history traits differ in the directions expected. However, age at maturity varied in a manner opposite to that expected, being earlier in the ponds with longer duration. Surface to volume ratio was not helpful in further resolving differences in these life history characters. This revised version was published online in August 2006 with corrections to the Cover Date.     

An Old Mom Keeps You Young: Mother’s Age at Last Birth and Offspring Longevity in Nineteenth-Century Utah

This study analyzes the intergenerational effects of late childbearing on offspring’s adult longevity in a population in Utah (United States) that does not display evidence of parity-specific birth control—a so-called natural fertility population. Studies have found that for women who experience late menopause and prolonged reproduction, aging is postponed and longevity is increased. This is believed to indicate female “robustness” and the impact of biological or genetic factors. If indeed there is a genetic component involved, one would expect to also find evidence for the intergenerational transmission of longevity benefits. Our study investigates the relationship between prolonged natural fertility of mothers and their offspring’s survival rates in adulthood. Gompertz regression models (N = 7,716) revealed that the offspring of mothers who were naturally fertile until a relatively advanced age lived significantly longer. This observed positive effect of late reproduction was not independent of but conditional upon survival of the mother to the end of her fecundity (defined as age 50). Offspring’s relative risks at death beyond age 50 were 6–12 percent lower than those of their counterparts born to mothers who had an average age at last birth. Our results, which account for various early, adult, and later-life conditions, as well as shared frailty, suggest that there is a positive relationship between mother’s age at last birth and offspring longevity, and strengthen the notion that age at menopause is a good predictor of this relationship.