The author systematically examines one of the important issues of information — establishing the market price. He introduces the concept of «search» — where a buyer wanting to get a better price, is forced to question sellers. The article deals with various aspects of finding the necessary information.

Economics of Information

A b s t r ac t Background Resistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin (mTOR) intracellular signaling pathway. In early studies, the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity. Methods In this phase 3, randomized trial, we compared everolimus and exemestane versus exemestane and placebo (randomly assigned in a 2:1 ratio) in 724 patients with hormone-receptor–positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease (or both). The primary end point was progression-free survival. Secondary end points included survival, response rate, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed. Results Baseline characteristics were well balanced between the two study groups. The median age was 62 years, 56% had visceral involvement, and 84% had hormone-sensitive disease. Previous therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade 3 or 4 adverse events were stomatitis (8% in the everolimus-plus-exemestane group vs. 1% in the placebo-plus-exemestane group), anemia (6% vs. <1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. <1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%). At the interim analysis, median progression-free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane, according to assessments by local investigators (hazard ratio for progression or death, 0.43; 95% confi dence interval [CI], 0.35 to 0.54; P<0.001). Median progression-free survival was 10.6 months and 4.1 months, respectively, according to central assessment (hazard ratio, 0.36; 95% CI, 0.27 to 0.47; P<0.001). Conclusions Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor–positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors. (Funded by Novartis; BOLERO-2 ClinicalTrials .gov number, NCT00863655.)

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Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer

Background: Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers are associated with increased sensitivity of these cancers to drugs that inhibit EGFR kinase activity. However, the role of such mutations in the pathogenesis of lung cancers is unclear. Methods: We sequenced exons 18-21 of the EGFR TK domain from genomic DNA isolated from 617 non-small-cell lung cancers (NSCLCs) and 524 normal lung tissue samples from the same patients and 36 neuroendocrine lung tumors collected from patients in Japan, Taiwan, the United States, and Australia and from 243 other epithelial cancers. Mutation status was compared with clinicopathologic features and with the presence of mutations in KRAS, a gene in the EGFR signaling pathway that is also frequently mutated in lung cancers. All statistical tests were two sided. Results: We detected a total of 134 EGFR TK domain mutations in 130 (21%) of the 617 NSCLCs but not in any of the other carcinomas, nor in nonmalignant lung tissue from the same patients. In NSCLC patients, EGFR TK domain mutations were statistically significantly more frequent in never smokers than ever smokers (51% versus 10%), in adenocarcinomas versus cancer of other histologies (40% versus 3%), in patients of East Asian ethnicity versus other ethnicities (30% versus 8%), and in females versus males (42% versus 14%; all P <.001). EGFR TK domain mutation status was not associated with patient age at diagnosis, clinical stage, the presence of bronchioloalveolar histologic features, or overall survival. The EGFR TK domain mutations we detected were of three common types: in-frame deletions in exon 19, single missense mutations in exon 21, and in-frame duplications/insertions in exon 20. Rare missense mutations were also detected in exons 18, 20, and 21. KRAS gene mutations were present in 50 (8%) of the 617 NSCLCs but not in any tumors with an EGFR TK domain mutation. Conclusions: Mutations in either the EGFR TK domain or the KRAS gene can lead to lung cancer pathogenesis. EGFR TK domain mutations are the first molecular change known to occur specifically in never smokers.

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Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers

Purpose Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial. Gefitinib monotherapy demonstrated unparalleled antitumor activity for a biologic agent, with less toxicity than docetaxel, in phase II trials in refractory, advanced non–small-cell lung cancer (NSCLC). This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC. Patients and Methods Patients received paclitaxel 225 mg/m2 and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. After a maximum of six cycles, daily gefitinib or placebo continued until disease progression. End points included overall...

/pdf/gefitinib-in-combination-with-paclitaxel-and-carboplatin-in-21pwcef2cv.pdf

Gefitinib in Combination With Paclitaxel and Carboplatin in Advanced Non–Small-Cell Lung Cancer: A Phase III Trial—INTACT 2

This paper empirically tests and rejects classical competitive theories of wage determination by examining differences in wages for equally skilled workers across industries. Human capital earnings functions are estimated using cross-sectional and longitudinal data from the CPS and QES. The major finding is that the dispersion in wages across industries as measured by the standard deviation in industry wage differentials is substantial. Furthermore, F tests of the joint significance of industry dummy variables are decisively rejected. These differences are very difficult to link to unobserved differences in ability or to compensating differentials for working conditions. Fixed effects models are estimated using two longitudinal data sets to control for constant, unmeasured worker characteristics that might bias cross-sectional estimates. Because measurement error is a serious problem in looking at workers who report changing industries, we use estimates of industry classification error rates to adjust the longitudinal results. In the fixed effects analysis, the industry wage differentials are sizable and are very similar to the cross-sectional estimates. In addition, the fixed effects estimates are robust under a variety of assumptions about classification errors and are similar using both data sets. These findings cast doubt on explanations of industry wage differentials based on unmeasured ability. Additional analysis finds that the industry wage structure is highly correlated for workers in small and large firms, in different regions of the U.S., and with varying job tenures. Finally, evidence is presented demonstrating that turnover has a negative relationship with industry wage differentials. These findings suggest that workers in high wage industries receive noncompetitive rents.

https://www.jstor.org/stable/pdfplus/1911072.pdf

Efficiency wages and the inter-industry wage structure

Our analysis replicates earlier studies of OSHA's inspection effects to see if, in the face of recordkeeping changes and new inspection targeting procedures, the relationships previously found still hold. The sizes and patterns of coefficients that we obtain in our analyses, including the lack of evidence that OSHA inspections (or the threat of them) reduce the injury rate, are consistent with those found earlier. We also analyze whether the new inspection procedure resulted in the reduction of reported injury rates among both inspected and uninspected plants. Consistent with an earlier paper, we find some downward bias in reporting among uninspectedfirms affected by the records-check procedure; however, we do not find this reporting bias among inspected plants.

Reestimating OSHA's Effects Have the Data Changed?

PURPOSETo perform a phase I clinical and pharmacologic study of ZD1694 (Tomudex, Alderley Park, United Kingdom), a new folate-based thymidylate synthase (TS) inhibitor, in patients with advanced malignancy.PATIENTS AND METHODSFrom February 1991 to January 1993, 61 patients with a range of solid tumor received 161 courses of ZD1694 given as a single 15-minute intravenous infusion every 3 weeks, at escalating doses from 0.1 to 3.5 mg/m2. Pharmacokinetic (PK) analysis was performed with the first two courses of treatment. There were 33 men and 28 women with a median age of 53 years (range, 21 to 73). Fifty-five patients (90%) had previously received chemotherapy.RESULTSReversible liver toxicity and dose-related gastrointestinal (GI) and bone marrow toxicity occurred at > or = 1.6 mg/m2. Liver function usually returned to normal with repeated treatment, but GI and bone marrow toxicities generally became more severe. No renal toxicity was observed. The maximum-tolerated dose (MTD) was 3.5 mg/m2, at which, in a...

Phase I trial of ZD1694, a new folate-based thymidylate synthase inhibitor, in patients with solid tumors

Our paper attempts to identify the types of data nee3ed to estimate tradeoffs between wages and fringe benefits (such as pensions); it also explores the usefulness for this estimation of one particular employer- based data set collected by gay Associates. We stress three things: first, that employer-based data sets are required. Second, because pensions and many other fringe benefits are actuarial functions of wages or salaries, these technical relationships must be accounted for in estimation. Third, to take account of unobservable heterogeneity of employees across employers, one must use econometric methods that control for these unobservable variables. The paper concludes with a discussion of our attempts to estimate the tradeoff between wages and fringe benefits using a unique database for 200 establishments that contains information on wages and actuarial valuations of employer costs of fringe benefits at three different job levels.

https://www.nber.org/system/files/working_papers/w0827/w0827.pdf

Estimating Wage-Fringe Trade-Offs: Some Data Problems

Examination of the impact of an antidiscrimination program on the relative economic position of minorities and women in the United States. Gender differences in relative employment and wage share; Results and discussion. (Abstract copyright EBSCO.)

https://www.jstor.org/stable/info/2522351

Robert S. Smith

Papers

Reestimating OSHA's Effects Have the Data Changed?

Phase I trial of ZD1694, a new folate-based thymidylate synthase inhibitor, in patients with solid tumors

Estimating Wage-Fringe Trade-Offs: Some Data Problems

The Estimated Impact of the Antidiscrimination Program Aimed at Federal Contractors

A Prelude to the Welfare State: The Origin of Workers' Compensation