Quality-adjusted survival with combination nab-paclitaxel + gemcitabine vs gemcitabine alone in metastatic pancreatic cancer: a Q-TWiST analysis

Objectives:

To use the Quality-Adjusted Time Without Symptoms or Toxicities (Q-TWiST) methodology to compare the quality-of-life and survival benefits associated with the combination of albumin-bound (nab)-paclitaxel and gemcitabine vs gemcitabine alone in the first-line treatment of metastatic pancreatic adenocarcinoma.

Methods:

Total survival time through 45 months was partitioned into time before disease progression without toxicity grade ≥3 (TWiST), time with adverse event grade ≥3 (TOX), and time of disease progression (REL). Mean Q-TWiST was calculated by multiplying time spent in each health state by its respective utility (i.e., TWiST?=?1.00; TOX/REL?=?0.50, 0–1 in sensitivity analyses). Non-parametric bootstrap 95% confidence intervals (CI) were derived to assess the significance of between-treatment differences in TOX, TWiST, REL, and Q-TWiST. A relative gain in Q-TWiST (vs mean overall survival of gemcitabine) of ≥10% and ≥15% was defined as clinically important and clearly clinically important, respectively.

Results:

Patients on nab-paclitaxel?+?gemcitabine spent a significantly longer time in every state and experienced significantly greater overall Q-TWiST (+1.7 months [95% CI?=?0.8, 2.7]) than those receiving gemcitabine alone (8.2 months [95% CI?=?7.5, 8.9] vs 6.5 months [95% CI?=?5.8, 7.0]), assuming base-case utilities of TOX/REL?=?0.50. This Q-TWiST gain ranged from 1.0 month (95% CI?=?0.1, 1.9), when REL/TOX utilities were both 0, to 2.5 months (95% CI?=?1.3, 3.7), when REL/TOX utilities were both 1. Relative gains in Q-TWiST were 21% in favor of nab-paclitaxel?+?gemcitabine in the base case, and ranged from 12–30% in sensitivity analyses.

Conclusions:

There are limitations to Q-TWiST analyses, e.g., imprecision when defining duration/severity of TOX and lack of prospective collection of utilities. This analysis addressed these issues via sensitivity analyses and conservative assumptions to show that nab-paclitaxel?+?gemcitabine results in statistically significant and clinically important gains in quality-adjusted survival, when compared to gemcitabine alone, in treatment-naive metastatic pancreatic adenocarcinoma patients.     

Perspective: A Review of Marketing Research on Product Design with Directions for Future Research

The authors provide synthesized summaries of research on product design conducted over the 20‐year period from 1995 to 2014, as well as suggestions for future research. Building on the conceptual model of product design proposed by Luchs and Swan, the current project describes research findings based on a review of 252 articles drawn from eight of the academic journals most influential to marketing thought, and identified by their inclusion of the terms “product design” or “industrial design” within their abstracts, subject terms, and/or author supplied keywords. Specifically, the authors provide integrated summaries of 25 product design subtopics organized within Luchs and Swan's original 11 product design research topic categories, which, in turn, address the following three general product design research categories: context and strategy, product design process, and product design consequences. These summaries are followed by suggested future research opportunities to address gaps in the literature. In addition to seeking inspiration for future research based on a review of extant research, the authors illustrate an approach for exploring research opportunities based on current and emerging industry trends, such as sustainability, the sharing economy, and the emergence of consumer‐oriented health and performance management products. For each identified industry trend, the authors provide illustrative design implications with consequent illustrative research opportunities. This balanced approach to identifying near‐term research opportunities based on extant research and based on industry trends, i.e., looking forward and externally, may in turn improve the potential impact of future research on both knowledge development and on industry practice.     

Dynamics and Politics in Regional Integration Arrangements: An Introduction

Overwhelming evidence links openness and economic growth. Inrecent years many developing countries have attempted to liberalizetheir trade and investment regimes, mostly through autonomousunilateral liberalization. At the same time, a growing numberof governments have begun to explore and participate in regionaltrading agreements. The agreements grant reciprocal trade preferencesto participating countries, resulting in discrimination againstnonmembers. The causes and consequences of regional integration have givenrise to an extensive and vigorous debate among both scholarsand policymakers. However, the quality of this debate has beenseriously hampered by the absence of clear analytical modelsand empirical evidence on many of the factors under discussion.Few of the recent arguments in favor of regional integrationarrangements have been satisfactorily formalized or tested.To address some of these issues, a World Bank research programfocuses on new and developing country aspects of regionalism.The program explores lacunae in the traditional static analysisof regional integration arrangements; addresses the dynamiceffects of integration, the economics of deep integration, andthe politics and political economy of regional integration arrangements;and compares regionalism with multilateralism. The articlesin this symposium address the topics of dynamics, politics,and political economy in regional integration agreements.     

Prosecutorial Resources, Plea Bargaining, and the Decision to Go to Trial

This article examines the strategic interaction between a defendantand a prosecutor during the plea bargaining process. A four-stagegame of incomplete information is developed where the defendant'sguilt or innocence is private information but the amount ofresources available to the prosecutor is common knowledge. Thebasic result of the article is that equilibrium is semiseparating;the plea offer is accepted by a proportion of the guilty defendantsand is rejected by all of the innocent defendants and the remainingguilty defendants. In this model an increase in the resourcesavailable to the prosecutor increases the proportion of guiltydefendants who accept plea offers. Although the prosecutor isunable to generate complete separation of the guilty and innocentdefendants through the plea bargaining process, prosecutorialresources are beneficial from a societal standpoint.     

Can Good Apples Be Mixed with Bad Economics? A Mengerian Critique of the Alchian and Allen Theorem

Abstract . The Alchian and Allen Theorem has been a popular staple of many economics classes since Armen Alchian and William Allen first introduced it in their well‐known text University Economics. The Theorem says that the addition of the same fixed cost to two similar goods will result in an increase of demand for the higher‐priced, “higher‐quality” good relative to the lower‐quality item. Response to the Theorem ranges from an informal comment that it is a “parlor trick” to it being called the “Third Law of Demand.” We review some of the literature, and use Carl Menger's economic analysis to challenge the Theorem's validity. Based on Menger's analysis, we conclude that the Theorem is not, in fact, a theorem because it is does not describe a general case, but instead only applies in some cases, thereby becoming, at best, a special case of Menger's more general analysis. Further, we find evidence that Alchian and Allen themselves unwittingly contradict their own argument elsewhere in one of their texts.     

Shooting the past? The modernisation of Conservative Party employment relations policy under David Cameron

Drawing on secondary data sources, the Conservative Party's efforts to modernise its approach to employment relations matters are discussed and critically scrutinised. Policy innovations are likely to be undermined by their mutual inconsistency with pervasive neoliberal, Eurosceptic and anti‐union values, indicating that on balance, any modernisation will be limited.     

The unintended consequences of PCAOB auditing Standard Nos. 2 and 3 on the reliability of preliminary earnings releases

Implementation of Public Company Accounting Oversight Board Auditing Standards No. 2 on internal control and No. 3 on documentation has delayed audit completion. However, due to market demand for timely disclosures, most firms maintain the same preliminary earnings release date even though the audit may not be complete as of that date. Results indicate revisions to preliminary announcements when filing the 10-K report would have been 35% lower during 2005 if the historical frequency of issuing earnings releases after the audit report date had not changed. Additionally, stock market reaction to impending revisions suggests lower reliability of preliminary earnings.