Lottery Spending: A Non-Parametric Analysis

We analyze the spending of individuals in the United States on lottery tickets in an average month, as reported in surveys. We view these surveys as sampling from an unknown distribution, and we use non-parametric methods to compare properties of this distribution for various demographic groups, as well as claims that some properties of this distribution are constant across surveys. We find that the observed higher spending by Hispanic lottery players can be attributed to differences in education levels, and we dispute previous claims that the top 10% of lottery players consistently account for 50% of lottery sales.     

Patented Biologically-inspired Technological Innovations： A Twenty Year View

1 Introduction Biomimetics or bionics is having an increasing role in innovation[1]. It offers the promise of novel routes to technological innovation; a recent paper highlighted the potential of studies of biological systems to initiate patents in the engineering sciences and technology[2]. Media coverage, particularly in business periodicals is increasing, for example, The Economist recently re- ported on the growth of biomimetics and its impact on technology[3]. There are two principal rou…     

Influence of Drug Binding on DNA Flexibility: A Normal Mode Analysis

Abstract

DNA-drug complexes are important because of their pharmacological interest but, in addition, they provide a useful model to study the essential aspects of DNA recognition processes. In order to investigate the influence of ligand binding on the dynamic properties of DNA we have carried out normal mode analysis for complexes with drugs of two types: a typical intercalator, 9-aminoacridine, and a typical groove binder, netropsin. Normal modes are analysed in terms of helicoidal parameter variations with special attention being paid to global deformations of the double helix. The results show that the influence of these two drugs is very different. Intercalation of 9-aminoacridine leads to an increase in the flexibility of the intercalated dinucleotide step, with notably larger vibrational amplitudes for both roll and twist parameters compared to free DNA. In contrast, the groove binding of netropsin induces a stiffening of the DNA segment which is in contact with the drug reflected by decreased vibrational amplitudes for backbone angles and inter base pair helicoidal parameters and an increase in vibrations for adjacent base pairs in terms of buckle and propeller twist.     

The Views of Healthcare Professionals,Drug Developers and Regulators on Information about Older People Needed for Rational Drug Prescription

Background

The ICH E7 guideline intends to improve the knowledge about medicines in geriatric patients. As a legislative document, it might not reflect the needs of healthcare professionals. This study investigated what information healthcare professionals, regulatory agencies and pharmaceutical industries consider necessary for rational drug prescribing to older individuals.

Methods and Findings

A 29-item-questionnaire was composed, considering the representation in trials, pharmacokinetics, efficacy, safety, and convenience of use in older individuals, with space for additions. Forty-three European professionals with an interest in medication for older individuals were included. In order to investigate their relevance, five items were included in a second questionnaire, with 11 control items. Median scores, differences between clinical and non-clinical respondents and response consistency were analysed. Consistency was present in 10 control items. Therefore, all items of the first questionnaire and the five additional items were analysed. Thirty-seven (86%) respondents returned the first questionnaire; 31/37 (84%) the second. Information about age-related differences in adverse events, locomotor effects, drug-disease interactions, dosing instructions, and information about the proportion of included 65+ patients was considered necessary by most respondents. Clinicians considered information significantly more important than the non-clinical respondents about the inclusion of 75+, time-until-benefit in older people, anticholinergic effects, drug-disease interactions, and convenience of use. Main study limitations are the focus on information for daily practice, while the ICH E7 guideline is a legislative document focused on market approval of a new medicine. Also, a questionnaire with a Likert scale has its limitations; this was addressed by providing space for comments.

Conclusions

This study reveals that items considered necessary are currently not included in the ICH E7 guideline. Also, clinicians’ and non-clinicians’ opinions differed significantly in 15% of the items. Therefore, all stakeholders should collaborate to improve the availability of information for the rational prescribing to older individuals.     

Decision-Making about Healthcare Related Tests and Diagnostic Strategies: User Testing of GRADE Evidence Tables

Objective

To develop guidance on what information to include and how to present it in tables summarizing the evidence from systematic reviews of test accuracy following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Methods

To design and refine the evidence tables, we used an iterative process based on the analysis of data from four rounds of discussions, feedback and user testing. During the final round, we conducted one-on-one user testing with target end users. We presented a number of alternative formats of evidence tables to participants and obtained information about users’ understanding and preferences.

Results

More than 150 users participated in initial discussions and provided their formal and informal feedback. 20 users completed one-on-one user testing interviews. Almost all participants preferred summarizing the results of systematic reviews of test accuracy in tabular format rather than plain text. Users generally preferred less complex tables but found presenting sensitivity and specificity estimates only as too simplistic. Users found the presentation of test accuracy for several values of prevalence initially confusing but modifying table layout and adding sample clinical scenarios for each prevalence reduced this confusion. Providing information about clinical consequences of testing result was viewed as not feasible for authors of systematic reviews.

Conclusion

We present the current formats for tables presenting test accuracy following the GRADE approach. These tables can be developed using GRADEpro guidelines development tool (www.guidelinedevelopment.org or www.gradepro.org) and are being further developed into electronic interactive tables that will suit the needs of different end users. The formatting of these tables, and how they influence result interpretation and decision-making will be further evaluated in a randomized trial.     

Academic Impact of Qualitative Studies in Healthcare: Bibliometric Analysis

Context

Although qualitative studies are becoming more appreciated in healthcare, the number of publications of quality studies remains low. Little is known about the frequency and characteristics of citation in qualitative studies.

Objective

To compare the academic impact of qualitative studies to that of two quantitative studies: systematic reviews and randomized controlled trials.

Methods

Publications in BMJ between 1997 and 2006 (BMJ’s median impact factor was 7.04 during this period) employing qualitative methods were matched to two quantitative studies appearing the same year using PubMed. Using Web of Science, citations within a 24-month publication period were determined. Additionally, three hypotheses were examined: qualitative studies are 1) infrequently cited in original articles or reviews; 2) rarely cited by authors in non-English-speaking countries; and 3) more frequently cited in non-medical disciplines (e.g., psychology or sociology).

Results

A total of 121 qualitative studies, 270 systematic reviews, and 515 randomised controlled trials were retrieved. Qualitative studies were cited a total of 1,089 times, with a median of 7.00 times (range, 0–34) for each study. Matched systematic reviews and randomized controlled trials were cited 2,411times and 1,600 times, respectively. With respect to citing documents, original articles and reviews exceeded 60% for each study design. Relative to quantitative studies, qualitative studies were cited more often by authors in English-speaking countries. With respect to subject area, medical disciplines were more frequently cited than non-medical disciplines for all three study designs (>80%).

Conclusion

The median number of citations for qualitative studies was almost the same as the median of BMJ’s impact factor during the survey period. For a suitable evaluation of qualitative studies in healthcare, it will be necessary to develop a reporting framework and include explicit discussions of clinical implications when reporting findings. Coordination between researchers and editors will be needed to achieve this goal.     

Cryptococcal Meningitis Treatment Strategies in Resource-Limited Settings: A Cost-Effectiveness Analysis

Background

Cryptococcal meningitis (CM) is the most common form of meningitis in Africa. World Health Organization guidelines recommend 14-d amphotericin-based induction therapy; however, this is impractical for many resource-limited settings due to cost and intensive monitoring needs. A cost-effectiveness analysis was performed to guide stakeholders with respect to optimal CM treatment within resource limitations.

Methods and Findings:

We conducted a decision analysis to estimate the incremental cost-effectiveness ratio (ICER) of six CM induction regimens: fluconazole (800–1,200 mg/d) monotherapy, fluconazole + flucytosine (5FC), short-course amphotericin (7-d) + fluconazole, 14-d of amphotericin alone, amphotericin + fluconazole, and amphotericin + 5FC. We computed actual 2012 healthcare costs in Uganda for medications, supplies, and personnel, and average laboratory costs for three African countries. A systematic review of cryptococcal treatment trials in resource-limited areas summarized 10-wk survival outcomes. We modeled one-year survival based on South African, Ugandan, and Thai CM outcome data, and survival beyond one-year on Ugandan and Thai data. Quality-adjusted life years (QALYs) were determined and used to calculate the cost-effectiveness ratio and ICER. The cost of hospital care ranged from $154 for fluconazole monotherapy to $467 for 14 d of amphotericin + 5FC. Based on 18 studies investigating outcomes for HIV-infected individuals with CM in resource-limited settings, the estimated mean one-year survival was lowest for fluconazole monotherapy, at 40%. The cost-effectiveness ratio ranged from $20 to $44 per QALY. Overall, amphotericin-based regimens had higher costs but better survival. Short-course amphotericin (1 mg/kg/d for 7 d) with fluconazole (1,200 mg/d for14 d) had the best one-year survival (66%) and the most favorable cost-effectiveness ratio, at $20.24/QALY, with an ICER of $15.11 per additional QALY over fluconazole monotherapy. The main limitation of this study is the pooled nature of a systematic review, with a paucity of outcome data with direct comparisons between regimens.

Conclusions

Short-course (7-d) amphotericin induction therapy coupled with high-dose (1,200 mg/d) fluconazole is “very cost effective” per World Health Organization criteria and may be a worthy investment for policy-makers seeking cost-effective clinical outcomes. More head-to-head clinical trials are needed on treatments for this neglected tropical disease. Please see later in the article for the Editors'' Summary.     

Conscientious Objection in Healthcare Provision: A New Dimension

The right to conscientious objection in the provision of healthcare is the subject of a lengthy, heated and controversial debate. Recently, a new dimension was added to this debate by the US Supreme Court's decision in Burwell vs. Hobby Lobby et al. which effectively granted rights to freedom of conscience to private, for‐profit corporations. In light of this paradigm shift, we examine one of the most contentious points within this debate, the impact of granting conscience exemptions to healthcare providers on the ability of women to enjoy their rights to reproductive autonomy. We argue that the exemptions demanded by objecting healthcare providers cannot be justified on the liberal, pluralist grounds on which they are based, and impose unjustifiable costs on both individual persons, and society as a whole. In doing so, we draw attention to a worrying trend in healthcare policy in Europe and the United States to undermine women's rights to reproductive autonomy by prioritizing the rights of ideologically motivated service providers to an unjustifiably broad form of freedom of conscience.     

我国医药分开政策目的及其策略分析

目的 进一步明确医药分开政策目的及策略。方法 采用文献回顾性研究法,对医药利益链条及其形成原因,以及解决策略进行系统性地总结和分析。结果 现有研究一是认为医疗服务提供方拥有垄断地位造成利益链条存在,因而提出消除垄断;二是认为扭曲的“白色”或不良的“灰色”激励机制造成利益链条存在,因而提出完善“白色”或消除“灰色”激励机制的综合策略。结论 医药利益链条产生更深层次的原因是,非营利性的公立医疗机构不合理地追求经济利益,医生采用不合理方式追求部分合理经济利益。因此,医药分开目的应是让公立医疗机构真正成为非营利机构,使医生依靠技术获得合理的经济回报,让公立医疗机构、医生、政府、患者、药品企业及流通商间激励相容。建议采用外部补偿和内部薪酬制度为重点的综合改革策略,形成各利益相关方激励相容的良好局面,自然消除公立医疗机构、医生与药品销售间利益链条。     

Helping Science and Drug Development to Succeed through Pharma-Academia Partnerships: Yale Healthcare Conference 2013

The theme of the 2013 Yale Healthcare Conference was “Partnerships in Healthcare: Cultivating Collaborative Solutions.” The April conference brought together leaders across several sectors of health care, including academic research, pharmaceuticals, information technology, policy, and life sciences investing. In particular, the breakout session titled “Taking R&D Back to School: The Rise of Pharma-Academia Alliances” centered on the partnerships between academic institutions and pharmaceutical companies. Attendees of the session included members of the pharmaceutical industry, academic researchers, and physicians, as well as graduate and professional students. The discussion was led by Dr. Thomas Lynch of Yale University. Several topics emerged from the discussion, including resources for scientific discovery and the management of competing interests in collaborations between academia and the pharmaceutical industry.     

Bayesian Hierarchical Pattern Mixture Models for Comparative Effectiveness of Drugs and Drug Classes Using Healthcare Data: A Case Study Involving Antihypertensive Medications

Comparative effectiveness research aims, in part, to provide evidence most relevant to clinical decision making. One decision relevant to hypertensive patients is which therapeutic drug class is the most safe and effective. In addition, once a drug class has been chosen it would be useful to know whether there are differences in effectiveness between drugs within class. Randomized trials are unlikely to provide sufficient evidence for answering these questions. We therefore propose a modeling approach that can be used to address the questions using administrative databases. We propose a Bayesian hierarchical model, where drugs are nested within their corresponding class. We account for the type of missing data that are common in these databases using a pattern mixture model. The methodology is illustrated using data from a comparative effectiveness study of antihypertensive medications.     

我国医疗联合体的利益相关者分析

随着医药卫生体制改革的不断深化,组建医疗联合体成为公立医院改革的新趋势。通过对医疗联合体利益相关者分析,组建区域性医疗联合体,对于联合体成员,包括核心医院和其他成员医院,还有政府或者患者都是有利的。因此,政府应在政策上对区域性医疗联合体给予更多支持,充分发挥医疗联合体的优势效应,促进公立医院的发展。     

Alternative Strategies to Reduce Maternal Mortality in India: A Cost-Effectiveness Analysis

Background

Approximately one-quarter of all pregnancy- and delivery-related maternal deaths worldwide occur in India. Taking into account the costs, feasibility, and operational complexity of alternative interventions, we estimate the clinical and population-level benefits associated with strategies to improve the safety of pregnancy and childbirth in India.

Methods and Findings

Country- and region-specific data were synthesized using a computer-based model that simulates the natural history of pregnancy (both planned and unintended) and pregnancy- and childbirth-associated complications in individual women; and considers delivery location, attendant, and facility level. Model outcomes included clinical events, population measures, costs, and cost-effectiveness ratios. Separate models were adapted to urban and rural India using survey-based data (e.g., unmet need for birth spacing/limiting, facility births, skilled birth attendants). Model validation compared projected maternal indicators with empiric data. Strategies consisted of improving coverage of effective interventions that could be provided individually or packaged as integrated services, could reduce the incidence of a complication or its case fatality rate, and could include improved logistics such as reliable transport to an appropriate referral facility as well as recognition of referral need and quality of care. Increasing family planning was the most effective individual intervention to reduce pregnancy-related mortality. If over the next 5 y the unmet need for spacing and limiting births was met, more than 150,000 maternal deaths would be prevented; more than US$1 billion saved; and at least one of every two abortion-related deaths averted. Still, reductions in maternal mortality reached a threshold (∼23%–35%) without including strategies that ensured reliable access to intrapartum and emergency obstetrical care (EmOC). An integrated and stepwise approach was identified that would ultimately prevent four of five maternal deaths; this approach coupled stepwise improvements in family planning and safe abortion with consecutively implemented strategies that incrementally increased skilled attendants, improved antenatal/postpartum care, shifted births away from home, and improved recognition of referral need, transport, and availability/quality of EmOC. The strategies in this approach ranged from being cost-saving to having incremental cost-effectiveness ratios less than US$500 per year of life saved (YLS), well below India''s per capita gross domestic product (GDP), a common benchmark for cost-effectiveness.

Conclusions

Early intensive efforts to improve family planning and control of fertility choices and to provide safe abortion, accompanied by a paced systematic and stepwise effort to scale up capacity for integrated maternal health services over several years, is as cost-effective as childhood immunization or treatment of malaria, tuberculosis, or HIV. In just 5 y, more than 150,000 maternal deaths would be averted through increasing contraception rates to meet women''s needs for spacing and limiting births; nearly US$1.5 billion would be saved by coupling safe abortion to aggressive family planning efforts; and with stepwise investments to improve access to pregnancy-related health services and to high-quality facility-based intrapartum care, more than 75% of maternal deaths could be prevented. If accomplished over the next decade, the lives of more than one million women would be saved. Please see later in the article for the Editors'' Summary     

Strategies for Diagnosis and Treatment of Suspected Leptospirosis: A Cost-Benefit Analysis

Background

Symptoms and signs of leptospirosis are non-specific. Several diagnostic tests for leptospirosis are available and in some instances are being used prior to treatment of leptospirosis-suspected patients. There is therefore a need to evaluate the cost-effectiveness of the different treatment strategies in order to avoid misuse of scarce resources and ensure best possible health outcomes for patients.

Methods

The study population was adult patients, presented with uncomplicated acute febrile illness, without an obvious focus of infection or malaria or typical dengue infection. We compared the cost and effectiveness of 5 management strategies: 1) no patients tested or given antibiotic treatment; 2) all patients given empirical doxycycline treatment; patients given doxycycline when a patient is tested positive for leptospirosis using: 3) lateral flow; 4) MCAT; 5) latex test. The framework used is a cost-benefit analysis, accounting for all direct medical costs in diagnosing and treating patients suspected of leptospirosis. Outcomes are measured in length of fever after treatment which is then converted to productivity losses to capture the full economic costs.

Findings

Empirical doxycycline treatment was the most efficient strategy, being both the least costly alternative and the one that resulted in the shortest duration of fever. The limited sensitivity of all three diagnostic tests implied that their use to guide treatment was not cost-effective. The most influential parameter driving these results was the cost of treating patients with complications for patients who did not receive adequate treatment as a result of incorrect diagnosis or a strategy of no-antibiotic-treatment.

Conclusions

Clinicians should continue treating suspected cases of leptospirosis on an empirical basis. This conclusion holds true as long as policy makers are not prioritizing the reduction of use of antibiotics, in which case the use of the latex test would be the most efficient strategy.     

Portrayal of the Human Resource Crisis and Accountability in Healthcare: A Qualitative Analysis of Ugandan Newspapers

Background

Uganda is one of the 57 countries with a critical shortage of health workers. The aim of this study was to determine how the human resources and health service crisis was covered in Ugandan newspapers and, in particular, how the newspapers attributed accountability for problems in the health services.

Methods

We collected all articles related to health workers and health services for the calendar year 2012 in the two largest national newspapers in Uganda (collection on daily basis) and in one local newspaper (collection on weekly basis). These articles were analysed qualitatively regarding the main themes covered and attribution of accountability.

Results

The two more urban national newspapers published 229 articles on human resources and health services in Uganda (on average over two articles per week), whereas the local more rural newspaper published only a single article on this issue in the 12 month period. The majority of articles described problems in the health service without discussing accountability. The question of accountability is raised in only 46% of articles (106 articles). The responsibility of the government was discussed in 50 articles (21%), and negligence, corruption and misbehaviour by individual health workers was reported in 56 articles (25%). In the articles about corruption (n=35), 60% (21 articles) mention corruption by health workers and 40% (14 articles) mention corruption by government officials. Six articles defended the situation of health workers in Uganda.

Conclusions

The coverage of accountability in the Ugandan newspapers surveyed is insufficient to generate informed debate on what political actions need to be taken to improve the crisis in health care and services. There exists not only an “inverse care law” but also an “inverse information law”: those sections of society with the greatest health needs and problems in accessing quality health care receive the least information about health services.     

Healthcare Service Utilization for Practicing Physicians: A Population-Based Study

Background

Physicians are considered to be the most informed consumers in the use of medical services since they have more information about diseases or medical technology. However, although plenty of researchers have suggested that different medical seeking behavior exists among physicians, very few empirical studies have been conducted to investigate differences in medical utilization between physicians and the general population.

Objective

We explored differences in the utilization of healthcare services between physicians and the general population using a population-based dataset.

Design

A cross-sectional study.

Participants

Data for this study were sourced from the Taiwan Longitudinal Health Insurance Database 2000. We included 1426 physicians and 1426 sex- and age-matched comparison subjects.

Methods

We used Wilcoxon-Mann-Whitney tests to explore differences in variables of healthcare resource utilization between physicians and comparison subjects. We further used Kruskal-Wallis tests to examine differences in variables of healthcare resource utilization between physician practice location and comparison subjects.

Results

We found that physicians had significantly fewer outpatient visits (13.2 vs. 15.7, p<0.001) and significantly lower outpatient costs (US$477 vs. US$680, p<0.001) than comparison subjects. Furthermore, physicians had lower total health service costs than comparison subjects (US$643 vs. US$1066, p<0.001). This indicates that the mean total health service costs in the year 2010 was 1.66-fold greater for comparison subjects than for physicians. We also found that there were significant differences in the mean number of outpatient services (p<0.001), outpatient costs (p = 0.001), inpatients costs (p = 0.018), and total costs (p = 0.001) among office-based physicians, hospital-based physicians, and comparison subjects. Specifically, Scheffe contrast tests showed that office-based physicians had significantly more outpatient visits (19.3 vs.10.7, p<0.001) and significantly higher outpatient costs (US$656 vs. US$402, p<0.001) than hospital-based physicians.

Conclusions

Physicians had less healthcare utilization than comparison subjects. Furthermore, hospital-based physicians had higher inpatient costs and less outpatient services and costs than office-based physicians.     

Follow-on Biologics: A New Play for Big Pharma: Healthcare 2010

The U.S. pharmaceutical industry plays a vital role in shaping the face of American healthcare. As an industry rooted in innovation, its continued evolution is inherent. With major patent expirations looming and thin product pipelines, the industry now must consider new directions to maintain growth and stability. Follow-on biologics, derived from living organisms and marketed after the patent expiration of similar therapies, represent a growing opportunity for big pharmaceutical firms, as discussed during Yale’s Healthcare 2010 conference in April. Key characteristics of follow-on biologics make them a worthwhile investment for big pharma companies: They command high prices, will likely have fewer entrants than generics due to high barriers to entry, and play to the existing strengths of big pharma firms. With the recent healthcare legislation providing the way for consistent Food and Drug Administration (FDA) regulation, the timing seems right to continue the push into this new and growing market.At a time when healthcare issues are on the mind of every American, it would serve us well to consider the future of one of the most influential players in the sector: pharmaceutical companies. National health expenditures for pharmaceutical products are hovering around 10 percent, meaning that one out of every 10 dollars that we, as a nation, spend on healthcare goes toward drugs. These drugs regulate our cholesterol levels, promote the growth of white blood cells in cancer patients, manage our restless leg syndrome, help us sleep better at night, and provide myriad other benefits to our health and well-being. Yet, for all the benefits that the pharmaceutical industry provides, it is also criticized by many for the expense of its products and the high profit margins that these products command. The growing popularity of biologics — treatments derived from living organisms, such as antibodies and interleukins — has particularly increased the price of drugs in the United States. The current price of the average biologic is more than 20 times that of a traditional, chemically synthesized small-molecule drug. There is a trade-off between high prices and innovative new therapies. Moreover, pharmaceutical companies themselves argue justifiably that prices account not only for the price of production, but also for the research and development (R&D) for that therapy as well as numerous others that did not make it all the way through the regulatory process and to the clinic.In recent years, we have witnessed the breakdown of the well-oiled innovation machinery of the traditional big pharma company. While R&D departments spent more and more (well over $1B per drug), they did not see promising results in the form of late-stage drug candidates [1]. Over time, this led to a strategic shift in portfolio management within big pharma companies toward an acquisition-heavy plan to build up their pipeline of drugs. In-house R&D projects were cut, and layoffs of scientific staff were rampant. This phenomenon continues, with 2009 bearing witness to the most mergers and acquisitions in the pharmaceutical industry to date. Industry-wide consolidation aimed to find complementary development projects and synergies in manufacturing and emerging markets. What has been the effect of all of this? The answer is not as hopeful as the pharmaceutical industry would have liked. A giant “patent cliff” still persists, referring to a number of blockbuster drugs that will go off patent over the next two years and cause a dramatic decrease in sales for big pharma firms. Without a strong pipeline to fill in the valley with new product sales, big pharma companies have begun scrambling to find new ways to generate revenue.Meanwhile, the biotech industry’s foray into therapeutics has been a wild success story. From the 1980s to the present, biologics have reshaped the face of medicine in many disease areas. The spawn of highly innovative, nimble biotech firms, biologic drugs are large, complex molecules grown in living cells rather than synthesized chemically like small molecules. For example, Enbrel is a fusion protein that acts as a tumor necrosis factor (TNF) inhibitor to stop inflammation. This drug is being widely prescribed for rheumatoid arthritis as well as psoriasis, among other indications, with sales last year reaching $5.9 billion, up 9.3 percent from 2008 [2]. Enbrel was first developed by Immunex and released in 1998. Immunex was acquired by a rival biotech firm, Amgen, in 2001 [3], and subsequent marketing of the drug in the United States was jointly undertaken by Amgen and Wyeth (now taken over by Pfizer in the mega-merger of 2009). Enbrel’s is the classic story of the modern biologic: a novel therapy developed at a small biotech firm and acquired or licensed up the food chain to feed bigger firms’ appetites for late-stage assets.Enbrel is by no means unique; there are many blockbuster biologics on the market. Like Enbrel, many of them will reach the end of their patent life soon. Enbrel’s patent expiration is set for 2012, at which time it will be exposed to potential competition from generic versions. Therefore, though there are many novel biologics therapies that can provide new ways of treating patients, there is also a huge opportunity for generic versions of biologics that did not exist even one decade ago. This opportunity is hard to quantify, but one recent estimate shows that biologics responsible for $20B in annual sales will go off patent by 2015 [4]. Unsurprisingly, small-molecule generics firms are flocking to this space. Teva, the world’s largest generics manufacturer, has partnered with the Lonza Group to make and sell so-called follow-on biologics. These treatments are similar, but not identical, to preceding biologics whose patents expired. Meanwhile, Novartis’s generics arm, Sandoz, has increased capacity in biomanufacturing to ramp up its efforts. Big pharma itself has made motions of interest in the business of follow-on biologics, as witnessed by the dedicated division of Merck, BioVentures, established in late 2008 for the development of follow-on biologics. Interestingly, even Pfizer is testing a follow-on version of Enbrel, now in phase 2 clinical trials [5]. With a big market opportunity and a number of firms interested, follow-on biologics will surely play an important role in shaping the future of the pharma industry.For large pharmaceutical firms, what is needed is a way to diversify and mitigate risk, a way to supplement their rollercoaster sales figures year after year. Follow-on biologics may be a smart play for big pharma companies. Like their generic cousins, biologics manufacturing has strong economies of scale that big pharma firms can leverage. But unlike generics, there are higher barriers to entry because of the technical challenges of manufacturing biologics and the necessary clinical proofs of equivalency. Pharmaceutical companies already are practiced at navigating the global clinical-trials arena and should be able to exercise a significant competitive advantage in this area, especially over the existing generics manufacturers attempting a play in the follow-on biologics market. It has been estimated that the investment necessary to bring a follow-on biologic to market is eight to 10 years and will cost $100-$200M [6]. This investment of time and capital is substantial and tends to favor larger firms with significant R&D budgets. However, to put the investment into perspective, this is only one-tenth of the cost of developing a full-scale innovative pharmaceutical product and has less associated risk of failure — a proposition that the big pharma industry should find appealing. Additionally, the trend for current follow-on biologics on the market in the European Union (EU) and United States has been to use traditional detailing and marketing practices to compete with branded products. This, too, puts big pharma at a competitive advantage over other players lacking an army of detailing pharmaceutical reps, who can use their established relationships with doctors and medical personnel to promote new follow-on biologics.One counter-argument to the case for a move into follow-on biologics is that the new healthcare reform, the Patient Protection and Affordable Care Act (PPACA), passed in March of this year will harm any would-be generic biologics makers with its 12-year exclusivity for branded biologics. However, while this length of time is significantly longer than the proposed five years that generics proponents pushed for, the surety of a secure path forward through the FDA for follow-on biologics outweighs the downside of lengthy biologics exclusivity. It is reasonable to hope that within two to three years, the FDA will have functional guidelines for the regulation of this nascent market. Now more than at any other time in the past, the ambiguity associated with government regulation is manageable. And if big pharma becomes more intentional about entering the follow-on biologics market, its powerful lobby, PhRMA, could influence the way that the details of the FDA regulations are written.If the pharma industry does find the follow-on biologics market appealing and makes a bet on it for supplementary revenue, what can we expect from the patient perspective? It could mean greater access at cheaper prices, but the dynamics are much more nuanced. The economics of the small-molecule generics market likely will not be transferrable to the follow-on biologics market. High barriers to entry, high fixed costs of manufacturing, and marketing expenses will more likely manifest themselves in a market that has a small number of firms with relatively small price drops upon introduction of follow-on therapies. In small-molecule generics, the price typically decreases by about 80 percent from the original branded drug price after one year of generic competition. However, in current follow-on markets in the EU, this has not been the case. Since its introduction of biosimilars regulation in 2004, the EU has successfully introduced numerous follow-on biologics for three classes of branded drugs. The results hint at what might be expected for U.S. firms: By 2008 in Germany, biosimilars had captured an estimated 14 percent to 30 percent market share and discounted prices by 25 percent [7]. The U.S. story of follow-on biologics will likely mirror that of EU biosimilars rather than that of small-molecule generics.With healthcare legislation passed and the inevitable refocusing on bending the cost curve in healthcare expenditures, big pharma firms may be able to boost their reputation with the public as well as their bottom line with a continued push into follow-on biologics. The decreased risk of approval and steady returns will help diversify pharmaceutical companies’ volatile revenue streams, while concurrently winning favorable public opinion by promoting price reductions for some of the most expensive drugs available. The cost savings to consumers will increase access for patients as FDA regulation is finalized and more and more follow-on biologics enter the market. This could be a win-win scenario for big pharma and for patients.