The economic costs of early stage prostate cancer

The economic costs of early stage prostate cancer are significant, and will likely increase as the proportion of older men grows in the population of industrialised nations. In the US, total costs have been estimated to range from US dollars 1.72 billion to US dollars 4.75 billion annually (1990 costs). Costs related to early stage prostate cancer arise from screening, staging and treatment. Cost-effectiveness models of population-based prostate cancer screening indicate that such screening could result in as much as US dollars 27.9 billion (1988 values) in charges to the US healthcare system. Evidence-based cancer-staging strategies would result in significant reduction of wasted expense. Rational allocation of healthcare dollars for prostate cancer screening and treatment may ultimately depend on data from randomised controlled trials.     

A predictive data-driven framework for endocrine prioritization: a triazole fungicide case study

The US Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a tiered screening approach to determine the potential for a chemical to interact with estrogen, androgen, or thyroid hormone systems and/or perturb steroidogenesis. Use of high-throughput screening (HTS) to predict hazard and exposure is shifting the EDSP approach to (1) prioritization of chemicals for further screening; and (2) targeted use of EDSP Tier 1 assays to inform specific data needs. In this work, toxicology data for three triazole fungicides (triadimefon, propiconazole, and myclobutanil) were evaluated, including HTS results, EDSP Tier 1 screening (and other scientifically relevant information), and EPA guideline mammalian toxicology study data. The endocrine-related bioactivity predictions from HTS and information that satisfied the EDSP Tier 1 requirements were qualitatively concordant. Current limitations in the available HTS battery for thyroid and steroidogenesis pathways were mitigated by inclusion of guideline toxicology studies in this analysis. Similar margins (3–5 orders of magnitude) were observed between HTS-predicted human bioactivity and exposure values and between in vivo mammalian bioactivity and EPA chronic human exposure estimates for these products’ registered uses. Combined HTS hazard and human exposure predictions suggest low priority for higher-tiered endocrine testing of these triazoles. Comparison with the mammalian toxicology database indicated that this HTS-based prioritization would have been protective for any potential in vivo effects that form the basis of current risk assessment for these chemicals. This example demonstrates an effective, human health protective roadmap for EDSP evaluation of pesticide active ingredients via prioritization using HTS and guideline toxicology information.     

Screening, prevention and socioeconomic costs associated with the treatment of colorectal cancer

Colorectal cancer (CRC), the third most prevalent cancer worldwide, imposes a significant economic and humanistic burden on patients and society. One study conservatively estimated the annual expenditures for colorectal cancer to be approximately dollars US 5.3 billion in 2000, including both direct and indirect costs. However, other investigators estimated inpatient costs alone incurred in the US in 1994 to be around dollars US 5.14 billion. Therefore, the economic burden of colorectal cancer in the US could be projected to be somewhere in the range of dollars US 5.5-6.5 billion by considering that inpatient costs approximate 80% of total direct costs. No worldwide data have been published, but assuming that the US represents 25-40% of total expenditures in oncology, as seen for breast and lung cancers, a rough estimate for colorectal cancer would be in the range of dollars US 14-22 billion. Screening helps increase patient survival by diagnosing colorectal cancer early. The ideal method among the four tests most used (faecal occult blood test, flexible sigmoidoscopy, colonoscopy and double contrast barium enema) has not been identified. Economic studies of colorectal cancer screening are complex because of the many variables involved, as well as the fact that the outcomes must be followed for many years, and the lack of consensus on screening guidelines. Intuitively, modelling colorectal cancer is one way to overcome these hurdles; published modelling studies predict colorectal cancer screening programs to be within the threshold of dollars US 40000 per life-year saved. The faecal occult blood test appears to be the only clearly effective test, both from a clinical and an economic viewpoint. Important limitations are the invasiveness and inconvenience of the screening procedures, except faecal occult blood test. Patients' comfort and satisfaction are essential in improving compliance with screening recommendations, which appears to be low even in the US (35% of the general population aged over 40 years and 60% of the high-risk population), the country with the highest awareness and compliance in the world. Since colorectal cancer is generally a disease of the elderly, its economic burden is expected to grow in the near future, mainly due to population aging. Potential avenues to pursue in order to contain or reduce the economic burden of colorectal cancer would be the design and implementation of efficient screening programmes, the improvement of patient awareness and compliance with screening guidelines, the development of appropriate prevention programs (i.e. primary and secondary), and earlier diagnosis.     

Estimating the economic impact of a half-day reduction in length of hospital stay among patients with community-acquired pneumonia in the US

ABSTRACT

Background: A recent study suggested that levofloxacin significantly reduces the hospital length of stay (LOS), by 0.5 days (p?=?0.02), relative to moxifloxacin in patients with community-acquired pneumonia (CAP). The current analysis evaluated the potential economic impact of this half-day reduction in LOS.

Methods: A cost model was developed to estimate the impact of a half-day reduction in LOS for CAP hospitalizations in the US. CAP incidence, hospitalization rate, and costs were obtained from published studies in PubMed and from publicly available government sources. The average daily cost of hospitalization was estimated for fixed costs, which comprise 59% of total inpatient costs. Costs from prior years were inflated to 2007 US dollars using the consumer price index. A range of cost savings, calculated using inpatient CAP costs from several studies, was extrapolated to the US CAP population.

Results: Using the Centers for Disease Control National Hospital Discharge estimate of 5.3 days LOS for CAP, and an average cost (2007 $US) of $13,009 per CAP hospitalization, a daily fixed cost of $1448 was estimated. The resultant half-day reduction in costs associated with LOS was $724/hospitalization (range $457 to $846/hospitalization). When fixed and variable costs were considered, the estimated savings were $1227.27/episode. The incidence of CAP was estimated to be 1.9% (5.7 million cases/year based on current population census), and the estimated rate of CAP hospitalization was 19.6% (1.1 million annual hospitalizations). At $13,009/CAP-related hospitalization, total fixed inpatient costs of $8.6 billion annually were projected. The half-day reduction in LOS would therefore generate potential annual savings of approximately $813 million (range $513 million to $950 million). When total costs (fixed plus variable) were estimated, the mean savings for a half-day reduction would be approximately $1227/episode (range of $775 to $1434) or $1.37 billion annually in the US CAP population (range of $871 million to $1.6 billion). Limitations include the use of a single study for the estimation of fixed costs but a diversity of sources used for estimates of other variables, and lack of data with respect to the effects on costs of diagnostic-related groups, discounted contracts, and capitated payments.

Conclusions: A relatively small decrease in LOS in CAP can have a substantial cost impact, with estimated savings of $457 to $846 per episode or $500-$900 million annually. Additional evaluation is warranted for interpreting these cost-savings in the context of current antibiotic prescribing patterns.     

IBC's Drug Discovery Technology - Europe 2001. 23-26 April 2001, Stuttgart, Germany

Specific sectors within the pharmaceutical industry are rapidly changing in response to technological advances. Genomics, high-throughput automated chemistry, high-throughput screening (HTS), ADME/Tox screening and informatics, provide new opportunities, but also create new bottlenecks. In addition, the selection and validation of biological targets, the proper design of compound libraries, data and knowledge management, and as the last and crucial step, the proof of therapeutic relevance by clinical trials, generates an enormous financial load on biotechnology and pharmaceutical companies. In the future, drug development costs might be reduced due to an ongoing pressure for shorter development cycles of new drugs. IBC's Drug Discovery Technology Europe 2001 conference addressed many aspects relevant to drug discovery technologies, and, along with its US partner conference, provides an annual meeting place for researchers and company executives to interact and exchange ideas.     

Etanercept Immunex

Immunex has developed and launched etanercept, a soluble TNF receptor (TNFR) fusion protein, for the treatment of early and moderate to severely active rheumatoid arthritis (RA). Etanercept was launched as a first-line agent in the US for the treatment of moderate-to-severe active RA in June 2000 [375481]. It can also be used in conjunction with methotrexate (MTX) in patients who do not respond adequately to MTX alone [303266], [310436]. It was launched in the EU in November 2000 [388846]. Enbrel was also launched for the treatment of polyarticular-course juvenile RA (JRA) patients who have an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs) in May 1999. Additionally, it is in phase III trials for psoriatic arthritis and a BLA filing for this indication is expected for the first half of 2001 [364948]. Etanercept was launched in the US in November 1998, for the treatment of moderate-to-severe RA in patients with inadequate responses to one or more DMARDs, or in combination with MTX in patients who do not respond adequately to MTX alone [306175]. The drug was subsequently approved by the US FDA for use as a first-line therapy to treat patients with moderately to severely active RA [375481]. In February 2000, Wyeth Europe received clearancefor etanercept in 15 EU countries by the EMEA for the treatment of active arthritis in adults when the response to DMARDs has been inadequate [354844]. It has since been launched in the UK (June 2000) [388840], and by October 2000 had been launched in all EU member states [388846]. In November 1998, the company filed a supplemental BLAfor the treatment of children and teenagers with moderately to severely active polyarticular course JRA. In May 1999, etanercept was approvedfor this indication by the US FDA and approvedfor this indication in Europe in February 2000 [307061], [310436], [326379]. The increasing understanding of the role of TNF in a number of other diseases has led to its clinical assessment in these areas. Following positive clinical results in phase II studies [317562], [315793], (320666], (359789], (373980] in patients with chronic heart failure, etanercept entered phase III trials for this indication in June 1999 [330068], and a BLA filing for this indication is expected in 2003 [396110]. Additionally, Immunex initiated a phase III trial of etanercept in psoriatic arthritis in March 2000, and as of May 2000, the company was planning a BLA filing for this indication in the first half of 2001 [364948]. An open-label trialfor the treatment of Crohn's disease is in progress in Belgium [367,039], and results from this trial were presented at Digestive Disease Week in May 2000 [379907]. While WO-09103553 claims the recombinant human receptor, the fusion protein consisting of the etanercept domain and the immunoglobulin region was disclosed in WO-09406476. In February 1997, US-05605690 was issued to Immunex for methods of using etanercept to treat diseases mediated by TNF. The patent also claims methods of using recombinant etanercept to decrease the levels of TNF in RA patients [235456]. In June 1999, Immunex strengthened its patent estate covering the product with a patent licensing agreement for Genentech's immunoadhesin patents covering the product [327250]. A royalty agreement with Serono SA and Immunex on sales of etanercept was agreed in 1999. The agreement reflected the strength of Ares-Serono's intellectual property status [352813]. In June 1999, Lehman Brothers predicted Immunex's sales at US $300 million in 1999, rising to peak annual sales of US $1.5 billion [328701]. Salesfor the drug's first full quarter on the market in 1999 were US $59.7 million [330068]. By November 1999 the drug had made sales of US $500 million; Immunex expects the drug will generate over US $2 billion in annual sales by 2004 [353185]. In September 2000, Merrill Lynch reported that if sales of the drug continue at the present rate then it is likely that demand will temporarily outstrip supply in 2001. Resolution of the supply issue is expected by 2002. Also in September 2000, Merrill Lynch lowered their estimate of ENBREL sales in 2001 from US $1 billion to $927 million. In the long-term, Merrill Lynch believe that the drug has the potential to exceed US $5 billion in sales in the US [382577].     

Etanercept. Immunex

Immunex has developed and launched etanercept, a soluble TNF receptor (TNFR) fusion protein, for the treatment of rheumatoid arthritis (RA). It has also been developed for various TNF-mediated conditions such as congestive heart failure, endometriosis and multiple sclerosis. Etanercept has been launched as a second-line agent in the US for the treatment of moderate-to-severe RA and can be used in conjunction with methotrexate in patients unresponsive to methotrexate alone. It is also available in the EU. In 2000, it was in phase III trials for psoriatic arthritis and an NDA filing for this indication was expected for the first half of 2001. In July 2001, the sBLA was filed, and in September 2001, the FDA granted the sBLA Priority Review status. As of January 2001, etanercept was in phase III trials for congestive heart failure, with sNDA filing expected in 2002; however, by March 2001, these had been halted, as it did not appear that statistical significance would be reached for the efficacy endpoints. Further data analysis was being undertaken at this time, before a final decision was taken. In April 2001, Merrill Lynch reported that development for this indication was to be halted. Sales for the drugs first full quarter on the market in 1999 were US $59.7 million. By November 1999 the drug had made sales of US $500 million; Immunex expected the drug to generate over US $2 billion in annual sales by 2004. In September 2000, Merrill Lynch reported that if sales of the drug continued at the present rate then it is likely that demand would temporarily outstrip supply in 2001. Resolution of the supply issue was expected by 2002. Also in September 2000, Merrill Lynch lowered their estimate of sales in 2001 from US $1 billion to $927 million. In the long-term, Merrill Lynch believed that the drug has the potential to exceed US $5 billion in sales in the US. In April 2001, Merrill Lynch predicted that etanercept prescribed for RA would generate sales of US $71 in 2002 rising to US $600 million in 2005. In October 2001, Morgani Stanley reported that Enbrel continues to be the primary source of revenue of Immunex (US $198.1 million). It was also reported that if launched for CHF, an estimated peak year revenue was likely to be US $500 million. The company maintains a website containing additional information about etanercept at http://www.enbrelinfo.com.     

Oprelvekin. Genetics Institute

Genetics Institute has developed and launched oprelvekin (rhIL-11; Neumega), a recombinant form of human IL-11. In November 1997, the FDA cleared oprelvekin for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in susceptible patients with non-myeloid malignancies 12703021. The product was launched at the end of 1997 [312556]. By December 1999, phase III trials for Crohn's disease (CD) were underway [363007]. Genetics Institute had commenced a 150-patient phase II trial for mild-to-moderate CD and mucositis and the company planned to file regulatory procedures for the indication of CD in 1999 [271210]. An oral formulation for this indication has been developed. Oprelvekin is also undergoing phase I clinical trials for colitis [396157], phase II clinical trials for rheumatoid arthritis [413835] and clinical trials for psoriasis [299644]. In March 1997, Wyeth-Ayerst became the licensee for Europe, Africa, Latin America and Asia (with the exception of Japan). Genetics Institute holds marketing rights for North America [239273]. In Japan, oprelvekin is being developed by Genetics Institute and Yamanouchi; phase III trials have commenced [295049] and were ongoing in May 2001 [411763]. In April 1996, analysts at Yamaichi estimated launch in 2001 and maximum annual sales of over yen 10 billion [215896]. In January 1998, Morgan Stanley Dean Witter predicted Yamanouchi's share of sales to be yen 1 billion in 2001, rising to yen 2 billion in 2002 [315458]. Sales of oprelvekin were US $34 million for Genetics institute in fiscal 2000 while, in July 2001, Credit Suisse First Boston estimated that this figure will be US $30 million and US $34 million in 2001 and 2002, respectively [416883].     

Duloxetine Eli Lilly

Duloxetine is a serotonin (5-HT) and norepinephrine (NE) uptake inhibitor in pre-registration for depression. In vivo studies demonstrate that duloxetine inhibits 5-HT and NE transporters and this may induce an antidepressant effect [159168]. In humans, duloxetine has a low affinity for most 5-HT subtypes and for muscarinic, histamine H1, alpha1-adrenergic, alpha2-adrenergic and dopamine D2 receptors [444103]. Thus, it is not surprising that the meta-analysis of four recent clinical studies suggests duloxetine is a potent and well-tolerated antidepressant [429723]. By December 2001, Lilly had filed an NDA for depression. The launch of duloxetine is planned for the second half of 2002 [434250], [436220]. In April 2002, filing for stress urinary incontinence was anticipated for later in 2002 [456894]. Analysts at Banc of America predicted in April 2002, that the drug will be launched in the first quarter of 2003. The company projects US $400 million in revenue in 2003 and anticipates duloxetine to reach peak sales of over US $1 billion [450920]. Analysts at Morgan Stanley, projected US $25 million in sales in the fourth quarter 2002, rising to US $900 million in 2006 [450937]. At the same time, Credit Suisse First Boston anticipated launch for late 2002, with US $220 million in duloxetine revenues in 2003 and US $457 million in 2004 [450936].     

High throughput pharmacology for drug discovery

High Throughput Screening (HTS) now plays an important role in the discovery of new lead compounds for novel therapeutic targets. The advantage of HTS over the conventional method, now termed as Low Throughput Screening (LTS), is that valuable compounds can be selected rapidly from a large number of samples with minimal human involvement. In spite of the growing awareness of HTS, the importance of the LTS in the drug discovery and development is still not changed. Advances in pharmacogenomics will also provide us many pharmacological targets, and thus increase the number of compounds that should be assayed by HTS and LTS. In this review, we will first describe the outline of HTS. We will next describe new approaches to develop and brush up the LTS: 1) screening method of drugs acting on ion channels by voltage-sensitive fluorescent dye, 2) functional assay method using reconstituted smooth muscle fiber, and 3) organ culture method as a useful model of vascular proliferative disease. These approaches, which work cooperatively with HTS, will contribute greatly to the development of new drugs.     

An integrated approach to fragment-based lead generation: philosophy, strategy and case studies from AstraZeneca's drug discovery programmes

Fragment-based lead generation (FBLG) has recently emerged as an alternative to traditional high throughput screening (HTS) to identify initial chemistry starting points for drug discovery programs. In comparison to HTS screening libraries, the screening sets for FBLG tend to contain orders of magnitude fewer compounds, and the compounds themselves are less structurally complex and have lower molecular weight. This report summarises the advent of FBLG within the industry and then describes the FBLG experience at AstraZeneca. We discuss (1) optimising the design of screening libraries, (2) hit detection methodologies, (3) evaluation of hit quality and use of ligand efficiency calculations, and (4) approaches to evolve fragment-based, low complexity hits towards drug-like leads. Furthermore, we exemplify our use of FBLG with case studies in the following drug discovery areas: antibacterial enzyme targets, GPCRs (melanocortin 4 receptor modulators), prostaglandin D2 synthase inhibitors, phosphatase inhibitors (protein tyrosine phosphotase 1B), and protease inhibitors (b-secretase).     

Evaluation of high-throughput genotoxicity assays used in profiling the US EPA ToxCast™ chemicals

Three high-throughput screening (HTS) genotoxicity assays—GreenScreen HC GADD45a-GFP (Gentronix Ltd.), CellCiphr p53 (Cellumen Inc.) and CellSensor p53RE-bla (Invitrogen Corp.)—were used to analyze the collection of 320 predominantly pesticide active compounds being tested in Phase I of US. Environmental Protection Agency’s ToxCast™ research project. Between 9% and 12% of compounds were positive for genotoxicity in the assays. However, results of the varied tests only partially overlapped, suggesting a strategy of combining data from a battery of assays. The HTS results were compared to mutagenicity (Ames) and animal tumorigenicity data. Overall, the HTS assays demonstrated low sensitivity for rodent tumorigens, likely due to: screening at a low concentration, coverage of selected genotoxic mechanisms, lack of metabolic activation and difficulty detecting non-genotoxic carcinogens. Conversely, HTS results demonstrated high specificity, >88%. Overall concordance of the HTS assays with tumorigenicity data was low, around 50% for all tumorigens, but increased to 74–78% (vs. 60% for Ames) for those compounds producing tumors in rodents at multiple sites and, thus, more likely genotoxic carcinogens. The aim of the present study was to evaluate the utility of HTS assays to identify potential genotoxicity hazard in the larger context of the ToxCast project, to aid prioritization of environmentally relevant chemicals for further testing and assessment of carcinogenicity risk to humans.     

Oligonucleotide Therapeutics--IBC Sixth International Conference. 3-5 May 1999, La Jolla, CA, USA

A wide array of strategies was presented for exploiting antisense oligonucleotides (AS ONs). Vitravene (ISIS Pharmaceuticals Inc), a first-generation phosphorothioate (PS) oligodeoxynucelotide (ODN) has been approved for use in the US and European markets for the treatment of CMV retinitis. A number of pharmaceutical companies introduced numerous compounds in both phase I and pivotal phase II clinical trials, for treatment of a wide range of diseases, including cancer, inflammation and viral agents. Advances in AS ON delivery were also described, including topical and oral routes of administration. New chemical modifications incorporated into second-generation oligonucleotides demonstrated superior potency and duration of action in a number of preclinical models. Finally, in response to the explosion in new genomic sequence information generated by the Human Genome Project, a number of companies are combining bioinformatics with high-throughput screening (HTS) to rapidly discover new drug targets. As a result, there was much excitement exhibited by researchers attending this meeting and a strong feeling that this new drug paradigm is delivering on its initial promise.     

Cellular platforms for HTS: three case studies

The field of cell-based screening is expanding rapidly as innovations in target selection and instrumentation increase the number of targets that can be efficiently screened in cellular formats. Cell-based screens can be configured to provide a broad range of data on chemical compound activity, mechanism of action and drugability. However, the decision to pursue a cell-based approach should not be made lightly, as cell-based assays can be challenging to implement in the high-throughput screening (HTS) laboratory. In this review, we describe three case studies in which targets were successfully interrogated in cell-based HTS, and highlight the necessary steps to ensure the validity of these screens.     

A pharmacoeconomic analysis of severe psoriasis therapy: a review of treatment choices and cost efficiency

INTRODUCTION: Psoriasis is a chronic, inflammatory disease afflicting 2% of the US population; it results in significant morbidity. The annual healthcare costs related to psoriasis are an estimated $11.3 billion and, with an expanding biologic market, an updated costs analysis is needed. AREAS COVERED: Current treatments, including systemic agents (acitretin, cyclosporine, methotrexate), phototherapies and all available biologics (adalimumab, etanercept, infliximab, alefacept, ustekinumab) appropriate for severe psoriasis are described mechanistically and with regard to their efficacy, quality-of-life improvements and side effects. A cost-efficacy model considering US health-system-based annual costs, clinical and quality-of-life improvements was created. Reported Psoriasis Area and Severity Index improvement of 75% from baseline (PASI-75) scores, Dermatology Life Quality Index (DLQI) improvements and estimated costs of medications are described. Annual costs ranged from $1330 for methotrexate to $48,731 for high-dose etanercept. The lowest cost per achieving DLQI minimally important difference was from phototherapy; the highest was from alefacept. The lowest costs per patient achieving PASI-75 was from methotrexate and the highest was from alefacept. EXPERT OPINION: Phototherapies and methotrexate offer high efficacy for their costs. Therapeutic approaches must be individualized for each patient given all considerations described.     

Genotoxicity screening: the slow march to the future

Genetic toxicology testing in drug discovery and development is slowly moving into the age of high-throughput screening (HTS). This has been helped by the development of new tools, as well as validation studies and data analysis to support their use in hit-to-lead or lead optimisation decisions. This review provides an overview of the current genetic toxicology methodologies and a few HTS methodologies. Comparisons are made between the predictivity of carcinogenesis that can be achieved in screening strategies as well as by the battery of regulatory tests. The importance of false-positive and false-negative calls at different stages in development is considered. There is a good prospect that in genetic toxicology, as in other areas of ADME-Tox, HTS will reduce the growing costs of carrying compounds with undesirable characteristics too far along the drug development process.     

Assessing the annual economic burden of preventing and treating anogenital human papillomavirus-related disease in the US: analytic framework and review of the literature

The anogenital human papillomavirus (HPV) is estimated to be the most commonly occurring sexually transmitted infection in the US. Comprehensive estimates of the annual economic burden associated with the prevention and treatment of anogenital HPV-related disease in the US population are currently unavailable. The purpose of this paper is to (i) outline an analytic framework from which to estimate the annual economic burden of preventing and treating anogenital HPV-related disease in the US; (ii) review available US literature concerning the annual economic burden of HPV; and (iii) highlight gaps in current knowledge where further study is particularly warranted. Among eight US studies identified that describe the annual economic burden pertaining to one or more aspects of anogenital HPV-related disease, three met the review eligibility criteria (published between 1990 and 2004, examined multiple facets of annual anogenital HPV-related economic burden, and clearly articulated the data and methods used in the estimation process). All costs were adjusted to 2004 US dollars. Estimates of the annual direct medical costs associated with cervical cancer were comparable across studies (range 300-400 million US dollars). In contrast, there was a wide range across studies for estimates of the annual direct medical costs associated with cervical intraepithelial neoplasia (range 700 million US dollars-2.3 billion US dollars). Only one study reported direct medical costs for anogenital warts (200 million US dollars) and routine cervical cancer screening (2.3 billion US dollars). No studies examined direct medical costs attributable to HPV-related anal, penile, vaginal or vulvar cancers, or the work and productivity losses resulting from time spent receiving medical care, morbidity or mortality. Current economic burden estimates would suggest annual direct medical costs associated with the prevention and treatment of anogenital warts and cervical HPV-related disease of at least 4 billion US dollars. This figure would likely rise to at least 5 billion US dollars per year if direct medical costs associated with other disease entities caused by the sexual transmission of HPV were included, with further additions to the economic burden totalling in the billions of dollars if work and productivity losses were incorporated, a research priority for future studies.     

Breast cancer management: quality-of-life and cost considerations

The purpose of this article was to provide a literature-based extensive overview of the quality-of-life and cost issues posed by the management of breast cancer. Incidence and mortality rates vary widely in different countries. Breast cancer accounts approximately for one-fifth of all deaths in women aged 40-50 years. The 1994-1998 incidence rate in the US population was on average 114.3 per 100 000 women. Treatment options include surgery, radiotherapy and drug therapy (cytotoxic and endocrine drugs). All treatment options affect patients' health-related quality of life (HR-QOL) in various ways. The use of cytotoxic agents has a particularly large HR-QOL impact. HR-QOL questionnaires are complex tools, not routinely used in breast cancer trials.Worldwide, around 10 million individuals develop cancer each year; this figure is expected to increase to 15 million in 2020. For all cancers, the total economic burden of this disease worldwide was projected by the authors to be in the range of $US 300-400 billion in 2001 (about $US 100-140 billion as direct costs and the remainder as indirect costs [morbidity and mortality]). According to the National Institute of Health (NIH), the total cost of cancer was estimated at $US 156.7 billion in 2001 in US ($US 56.4 billion as direct costs, $US 15.6 as indirect morbidity costs, and $US 84.7 billion as indirect mortality costs). Based on limited information, in the US, breast cancer can be projected to account for about one-fifth/one-fourth of the total cost of cancer. Breast cancer treatment costs are higher in the US than in other developed countries. Both direct and indirect costs are dependent on disease stage. The per-patient costs for initial care in 1992 were estimated at $US 10 813, for continuing care at $US 1084 and for terminal care at $US 17 886. Stage-specific costs provide information for cost-effectiveness analyses of cancer-control initiatives, such as screening programmes. Economic studies on breast cancer are heterogeneous, and the cost estimates made are not easily generalisable. The cost of treatment for breast cancer in developing countries is < or =5% of that in developed regions.