The cost of biopharmaceutical R&D: Is biotech different?

The costs of developing the types of new drugs that have been pursued by traditional pharmaceutical firms have been estimated in a number of studies. However, similar analyses have not been published on the costs of developing the types of molecules on which biotech firms have focused. This study represents a first attempt to get a sense for the magnitude of the R&D costs associated with the discovery and development of new therapeutic biopharmaceuticals (specifically, recombinant proteins and monoclonal antibodies [mAbs]). We utilize drug-specific data on cash outlays, development times, and success in obtaining regulatory marketing approval to estimate the average pre-tax R&D resource cost for biopharmaceuticals up to the point of initial US marketing approval (in year 2005 dollars). We found average out-of-pocket (cash outlay) cost estimates per approved biopharmaceutical of $198 million, $361 million, and $559 million for the preclinical period, the clinical period, and in total, respectively. Including the time costs associated with biopharmaceutical R&D, we found average capitalized cost estimates per approved biopharmaceutical of $615 million, $626 million, and $1241 million for the preclinical period, the clinical period, and in total, respectively. Adjusting previously published estimates of R&D costs for traditional pharmaceutical firms by using past growth rates for pharmaceutical company costs to correspond to the more recent period to which our biopharmaceutical data apply, we found that total out-of-pocket cost per approved biopharmaceutical was somewhat lower than for the pharmaceutical company data ($559 million vs $672 million). However, estimated total capitalized cost per approved new molecule was nearly the same for biopharmaceuticals as for the adjusted pharmaceutical company data ($1241 million versus $1318 million). The results should be viewed with some caution for now given a limited number of biopharmaceutical molecules with data on cash outlays, different therapeutic class distributions for biopharmaceuticals and for pharmaceutical company drugs, and uncertainty about whether recent growth rates in pharmaceutical company costs are different from immediate past growth rates. Copyright © 2007 John Wiley & Sons, Ltd.

Economic return of clinical trials performed under the pediatric exclusivity program.

CONTEXT: In 1997, Congress authorized the US Food and Drug Administration (FDA) to grant 6-month extensions of marketing rights through the Pediatric Exclusivity Program if industry sponsors complete FDA-requested pediatric trials. The program has been praised for creating incentives for studies in children and has been criticized as a "windfall" to the innovator drug industry. This critique has been a substantial part of congressional debate on the program, which is due to expire in 2007. OBJECTIVE: To quantify the economic return to industry for completing pediatric exclusivity trials. DESIGN AND SETTING: A cohort study of programs conducted for pediatric exclusivity. Nine drugs that were granted pediatric exclusivity were selected. From the final study reports submitted to the FDA (2002-2004), key elements of the clinical trial design and study operations were obtained, and the cost of performing each study was estimated and converted into estimates of after-tax cash outflows. Three-year market sales were obtained and converted into estimates of after-tax cash inflows based on 6 months of additional market protection. Net economic return (cash inflows minus outflows) and net return-to-costs ratio (net economic return divided by cash outflows) for each product were then calculated. MAIN OUTCOME MEASURES: Net economic return and net return-to-cost ratio. RESULTS: The indications studied reflect a broad representation of the program: asthma, tumors, attention-deficit/hyperactivity disorder, hypertension, depression/generalized anxiety disorder, diabetes mellitus, gastroesophageal reflux, bacterial infection, and bone mineralization. The distribution of net economic return for 6 months of exclusivity varied substantially among products (net economic return ranged from -$8.9 million to $507.9 million and net return-to-cost ratio ranged from -0.68 to 73.63). CONCLUSIONS: The economic return for pediatric exclusivity is variable. As an incentive to complete much-needed clinical trials in children, pediatric exclusivity can generate lucrative returns or produce more modest returns on investment.

No more nonsense

Discusses the approach of the courts to the quantification of beneficial interests in the family home in the event of a relationship breakdown. Assesses the clarification provided by the Court of Appeal ruling in Fowler v Barron on whether the respondent was the sole beneficial owner of a property purchased with his former partner, by means of a significant cash contribution from him and a mortgage in both their names, focusing on whether he could rebut the presumption that they held the property as joint tenants in equity where it was registered in joint names. [From Legal Journals Index]

Financing of SME's: an asset side story

The main sources of financing for small and medium sized enterprises (SMEs) are equity (internally generated cash), trade credit paid on time, long and short term bank credits, delayed payment on trade credit and other debt. The marginal costs of each financing instrument are driven by asymmetric information (cost of gathering and analysing information) and transactions costs associated with non-payment (costs of collecting and selling collateral). According to the Pecking Order Theory, firms will choose the cheapest source in terms of cost. In the case of the static trade-off theory, firms choose finance so that the marginal costs across financing sources are all equal, thus an additional Euro of financing is obtained from all the sources whereas under the Pecking Order Theory the source is determined by how far down the Pecking Order the firm is presently located. In this paper, we argue that both of these theories miss the point that the marginal costs are dependent of the use of the funds, and the asset side of the balance sheet primarily determines the financing source for an additional Euro. An empirical analysis on a unique dataset of Portuguese SME's confirms that the composition of the asset side of the balance sheet has an impact of the type of financing used and the Pecking Order Theory and the traditional Static Trade-off theory are rejected.

Impacts of wildlife on household food security and income in northeastern Tanzania

We evaluated the impacts of wildlife on household food security and income in three semi-arid villages adjacent to Lake Manyara National Park (LMNP) and Mkomazi Game Reserve (MGR) in Northeastern Tanzania. Survey data were collected using both household interviews and human-wildlife conflict related archive information from the village government offices. Crop destruction by wildlife influenced both household food security and cash income. Crop damage to households was, on average, 0.08 ton/annum, equivalent to two months household loss of food and reduced household cash income by 1.3%. A combination of measures is proposed as incentives for conservation. These include provision of economic incentives, soft loans to initiate non-farm (e.g., ecotourism, business enterprises) projects to ease dependency on natural resources, increasing of reserves buffer zones and fencing of reserves.

Bolsa Familia Program and school enrolment: An analysis of the 2010 Brazilian demographic census

The Bolsa Família Program goal is to promote social development and poverty reduction, through the direct transfer of conditional cash, in association with other social programs. This study aims to analyze whether Bolsa Família had an association with children’s school attendance, which is one of the educational conditions of the program. Our main hypothesis is that children living in households receiving Bolsa Família had greater chances of attending school. Data from the Ministry of Social Development and Combating Famine indicated that children living in households with Bolsa Família had greater school enrolment levels. By using data from the 2010 Demographic Census, collected by the Brazilian Institute of Geography and Statistics (IBGE), some descriptive analyzes and binary logistic regression models were performed for different thresholds of household per capita income. These estimates were made by comparing children who lived in households receiving Bolsa Família to those children not receiving the program. We took into consideration characteristics about the household, mothers, and children. The results were clustered by the municipality of residence of the child. In all income thresholds, children benefi ting from Bolsa Família were more likely to be enrolled in school, compared to children not receiving the benefi t.

Ownership Patterns and Control in Turkish Listed Companies

The purpose of this paper is to document the prevalent ownership concentration, structure and control in the top 100 companies listed on the Istanbul Stock Exchange. The results are discussed in the context of emerging corporate governance trends in Turkey. Where appropriate, comparisons with other countries are provided. The results of the study indicate that ownership of Turkish companies is highly concentrated, families being the dominant shareholders. The separation of ownership and control among Turkish companies is mainly achieved through pyramidal ownership structures and the presence of big business groups. However, the cash flow and voting rights in Turkish companies are relatively more aligned compared to other family–ownership–dominated insider–system countries.

Accruals accounting in the public sector: A road not always taken

The move from cash to accruals accounting by many governments is viewed as an aspect of an ongoing New Public Management agenda designed to achieve a more business-like and performance-focused public sector. Proponents argue that accruals accounting provides more appropriate information for decision makers and ultimately leads to a more efficient and effective public sector. The transition from cash to accruals accounting for UK central government departments was announced in the early 1990s and was embedded within approximately ten years. At that time there were clear indications that analogous changes, following a similar timeline, would occur in the Republic of Ireland (RoI). In reality, the changes were significantly less extensive. Utilising document analysis and interviews with key actors, this paper considers why a functioning accruals system was established in the UK whereas in the RoI the change to accruals accounting was a ‘road not taken’.

The Perils of Moviegoing in America, 1896-1950

The Perils of Moviegoing in America is a film history that examines the various physical and (perceived) moral dangers facing audiences during the first fifty years of film exhibition.

Chapter 1: “Conflagration”
As early as 1897, a major fire broke out at a film exhibition in San Francisco, with flames burning the projectionist and nearby audience members. From that point until the widespread adoption of safety stock in 1950, fires were a very common movie-going experience. Hundreds of audience members lost their lives in literally thousands of theatre fires, ranging from early nickelodeons to the movie palaces of the thirties and forties.

Chapter 2: “Thieves Among Us”
Bandits robbed movie theatres on hundreds of occasions from the early days of film exhibition through the end of the Great Depression. They held up ticket booths, and they dynamited theatre safes. They also shot theatre managers, ushers, and audience members, as a great many of the robberies occurred while movies were playing on the screens inside.

Chapter 3: “Bombs Away”
Bombings at movie theatres became common in small towns and large cities on literally hundreds of occasions from 1914 to the start of World War II. Some were incendiary bombs, and some were stench bombs; both could be fatal, whether due to explosions or to the trampling of panicked moviegoers

Chapter 4: “It’s Catching”
Widespread movie-going in the early 20th century provoked an outcry from numerous doctors and optometrists who believed that viewing films could do irreparable harm to the vision of audience members. Medical publications (including the Journal of the American Medical Association) published major studies on this perceived problem, which then filtered into popular-audience magazines and newspapers.

Chapter 5: “The Devil’s Apothecary Shops”
Sitting in the dark with complete strangers proved worrisome for many early filmgoers, who had good reason to be concerned. Darkness meant that prostitutes could easily work in the balconies of some movie theatres, as could “mashers” who molested female patrons (and sometimes children) after the lights were dimmed. That was all in addition to the various murderers who used the cover of darkness to commit their crimes at movie theatres.

Chapter 6: “Blue Sundays”
Blue laws were those regulations that prohibited businesses from operating on Sundays. Most communities across the US had such legislation on their books, which by the nickelodeon era were at odds with the thousands of filmgoers who went to the movies every Sunday. Theatre managers were often arrested, making newspaper headlines over and over again. Police sometimes even arrested entire film audiences as accomplices in the Blue Law violations.

Chapter 7: “Something for Nothing”
In an effort to bolster ticket sales, many movie theatres in the 1910s began to hold lotteries in which lucky audience members won cash prizes; by the time of the Great Depression, lotteries like “Bank Night” became a common aspect of the theatre-going enterprise. However, reception studies have generally overlooked the intense (and sometimes coordinated) efforts by police, politicians, and preachers to end this practice, which they viewed as illegal and immoral gambling.

Ascending Out of Poverty: An analysis of family histories in Kenya

This paper looks at inheritance through minimally-structured interviews with several generations of Kenyan families, seeking to explain that the how and why of poverty can be understood in the wider family context. Five main routes for ascending out of poverty were identified: (1) the gradual accumulation of resources due to income deriving from cash crops; (2) the gradual accumulation of resources due to income from non-farm work, including remittances from family member who have moved away for work; (3) the role of education, particularly skills training opposed to academic qualification, in helping provide employment; (4) accessing financial assets through support both from extended family members and from informal support mechanisms; (5) stability and benefits accruing from long-term strategic planning, including entrepreneurial activity. Both the ascent out of and the descent into poverty can be better conceived as processes, rather than due to chains of discrete events or specific ‘shocks’.

Slievabawnogue Housing:Two Dwellings in A Disused Quarry

This project involves the construction of a dwelling in the outskirts of Dublin City. Situated in a disused quarry, the house act as an inhabited bridge, spanning between natural and man made outcrops, service structures and a shared entrance staircase. The houses language derives from the structure necessary to achieve these spans.
The section internally is modeled to present a variety of scales of spaces. More intimate living spaces and bedrooms occur in a lower, north-facing wing. Taller living spaces address the south.

Incorporating rainwater harvesting, wood-gasifying boilers, on site wind powered electrical generation, solar thermal panels and very high levels of insulation the houses are close to energy neutral. The fact that the house is constructed in massive timber construction means that 250 tonnes of carbon are sequestered in its construction. The design includes a 25yar replanting strategy to replace the existing coniferous-forested surrounds with native species in a coppiced planting strategy to allow ongoing fuel for the house, and cash crops to be sold on.

Located in an area of outstanding natural beauty the planning and design of the house involved research into patterns of rural development, the relationship between man made interventions and the natural landscape and the technology of the vernacular. This latter research forms part of the themes being explored under the Kevin Kieran Arts Council / OPW Bursary

Aims / Objectives Questions

1 To design and construct a low energy place to dwell.
2 To investigate the relationship between man-made interventions and new construction in an area of outstanding natural beauty.
3 To derive a language of construction that is contemporary in nature but refers to precedents embedded in the vernacular.
4 To develop a low-carbon form of construction that allows the construction of the house to act to sequester carbon
5 To make a contemporary addition in sympathy with the qualities of the existing site

The physical activity loyalty card scheme:Development and application of a novel system for incentivizing behaviour change

In the Public Health White Paper "Healthy Lives, Healthy People" (2010), the UK Government emphasised using incentives and "nudging" to encourage positive, healthy behaviour changes. However, there is little evidence that nudging is effective, in particular for increasing physical activity. We have created a platform to research the effectiveness of health-related behaviour change interventions and incentive schemes. The system consists of an outward-facing website, incorporating tools for incentivizing behaviour change, and a novel physical activity monitoring system. The monitoring system consists of the "Physical Activity Loyalty Card", which contains a passive RFID tag, and a contactless sensor network to detect the cards. This paper describes the application of this novel web-based system to investigate the effectiveness of non-cash incentives to "nudge" adults to undertake more physical activity. © 2012 ICST Institute for Computer Science, Social Informatics and Telecommunications Engineering.

Why Do Firms Pay Dividends?: Evidence from an Early and Unregulated Capital Market

Why do firms pay dividends? To answer this question, we use a hand-collected data set of companies traded on the London stock market between 1825 and 1870. As tax rates were effectively zero, the capital market was unregulated, and there were no institutional stockholders, we can rule out these potential determinants ex ante. We find that, even though they were legal, share repurchases were not used by firms to return cash to shareholders. Instead, our evidence provides support for the information–communication explanation for dividends, while providing little support for agency, illiquidity, catering, or behavioral explanations. © The Authors 2013. Published by Oxford University Press [on behalf of the European Finance Association]. All rights reserved.

Disordered vascular compliance in haemochromatosis

Background: A relationship may exist between body iron stores, endothelial dysfunction and overall cardiovascular risk.

Aims: To compare vascular compliance, biochemical endothelial function and antioxidant status between patients with homozygous hereditary haemochromatosis and healthy controls.

Methods: Haemochromatosis patients and healthy controls were recruited. Measures of vascular compliance were assessed by applanation tonometry. Serological markers of endothelial function (plasma lipid hydroperoxides, cell adhesion molecules), antioxidant levels (ascorbate, lipid soluble antioxidants) and high-sensitivity C-reactive protein (CRP) were also measured.

Results: Thirty-five hereditary haemochromatosis patients (ten females, mean age 54.6) and 36 controls (27 female, mean age 54.0) were recruited. Haemochromatosis patients had significantly higher systolic and diastolic blood pressures. Pulse wave velocity (PWV) was significantly higher in male haemochromatosis patients (9.90 vs. 8.65 m/s, p = 0.048). Following adjustment for age and blood pressure, male haemochromatosis patients continued to have a trend for higher PWVs (+1.37 m/s, p = 0.058). Haemochromatosis patients had significantly lower levels of ascorbate (46.11 vs. 72.68 lmol/L, p = 0.011), retinol (1.17 vs. 1.81 lmol/L, p = 0.001) and g-tocopherol (2.51 vs. 3.14 lmol/L, p = 0.011). However, there was no difference in lipid hydroperoxides (0.46 vs. 0.47 nmol/L, p = 0.94), cell adhesion molecule levels (ICAM: 348.12 vs. 308.03 ng/mL, p = 0.32 and VCAM: 472.78 vs. 461.31 ng/mL, p = 0.79) or high-sensitivity CRP (225.01 vs. 207.13 mg/L, p = 0.32).

Conclusions: Haemochromatosis is associated with higher PWVs in males and diminished antioxidants across the sexes but no evidence of endothelial dysfunction or increased lipid peroxidation.