Reporting bias in drug trials submitted to the Food and Drug Administration: review of publication and presentation.

BackgroundPrevious studies of drug trials submitted to regulatory authorities have documented selective reporting of both entire trials and favorable results. The objective of this study is to determine the publication rate of efficacy trials submitted to the Food and Drug Administration (FDA) in approved New Drug Applications (NDAs) and to compare the trial characteristics as reported by the FDA with those reported in publications.Methods and findingsThis is an observational study of all efficacy trials found in approved NDAs for New Molecular Entities (NMEs) from 2001 to 2002 inclusive and all published clinical trials corresponding to the trials within the NDAs. For each trial included in the NDA, we assessed its publication status, primary outcome(s) reported and their statistical significance, and conclusions. Seventy-eight percent (128/164) of efficacy trials contained in FDA reviews of NDAs were published. In a multivariate model, trials with favorable primary outcomes (OR = 4.7, 95% confidence interval [CI] 1.33-17.1, p = 0.018) and active controls (OR = 3.4, 95% CI 1.02-11.2, p = 0.047) were more likely to be published. Forty-one primary outcomes from the NDAs were omitted from the papers. Papers included 155 outcomes that were in the NDAs, 15 additional outcomes that favored the test drug, and two other neutral or unknown additional outcomes. Excluding outcomes with unknown significance, there were 43 outcomes in the NDAs that did not favor the NDA drug. Of these, 20 (47%) were not included in the papers. The statistical significance of five of the remaining 23 outcomes (22%) changed between the NDA and the paper, with four changing to favor the test drug in the paper (p = 0.38). Excluding unknowns, 99 conclusions were provided in both NDAs and papers, nine conclusions (9%) changed from the FDA review of the NDA to the paper, and all nine did so to favor the test drug (100%, 95% CI 72%-100%, p = 0.0039).ConclusionsMany trials were still not published 5 y after FDA approval. Discrepancies between the trial information reviewed by the FDA and information found in published trials tended to lead to more favorable presentations of the NDA drugs in the publications. Thus, the information that is readily available in the scientific literature to health care professionals is incomplete and potentially biased

Exact and Approximate Determinization of Discounted-Sum Automata

A discounted-sum automaton (NDA) is a nondeterministic finite automaton with edge weights, valuing a run by the discounted sum of visited edge weights. More precisely, the weight in the i-th position of the run is divided by $\lambda^i$, where the discount factor $\lambda$ is a fixed rational number greater than 1. The value of a word is the minimal value of the automaton runs on it. Discounted summation is a common and useful measuring scheme, especially for infinite sequences, reflecting the assumption that earlier weights are more important than later weights. Unfortunately, determinization of NDAs, which is often essential in formal verification, is, in general, not possible. We provide positive news, showing that every NDA with an integral discount factor is determinizable. We complete the picture by proving that the integers characterize exactly the discount factors that guarantee determinizability: for every nonintegral rational discount factor $\lambda$, there is a nondeterminizable $\lambda$-NDA. We also prove that the class of NDAs with integral discount factors enjoys closure under the algebraic operations min, max, addition, and subtraction, which is not the case for general NDAs nor for deterministic NDAs. For general NDAs, we look into approximate determinization, which is always possible as the influence of a word's suffix decays. We show that the naive approach, of unfolding the automaton computations up to a sufficient level, is doubly exponential in the discount factor. We provide an alternative construction for approximate determinization, which is singly exponential in the discount factor, in the precision, and in the number of states. We also prove matching lower bounds, showing that the exponential dependency on each of these three parameters cannot be avoided. All our results hold equally for automata over finite words and for automata over infinite words

The Efficacy of New York\u27s Qualified Prohibition on NDAs and Reforms that Can Protect Sexual Harassment Survivors

The numerous sexual harassment scandals that were uncovered following the Harvey Weinstein exposé have at least one very positive byproduct: new state legislation aimed to protect and combat sexual misconduct in the workplace. New York is leading the charge by creating a legislative framework that protects a broader spectrum of workers against sexual harassment in the workplace. The State’s 2019 fiscal year budget substantiates the commitment to empower survivors and protect those who may be future targets of sexual harassment in their workplaces. As part of this framework, the State’s human rights laws now extend to and protect independent contractors, who ordinarily would have limited federal protections against sexual harassment because they are ineligible for Title VII protection. In another forging step, New York now prohibits employers from including or agreeing to include a nondisclosure agreement (NDA) in a settlement agreement regarding a sexual harassment claim, unless the employee seeks the confidentiality. This prohibition is a step in the right direction as new data shows the increasing prevalence of NDAs in the workplace, often silencing instrumental employee speech

Human Factors in Information-Age Trade Secret Protection

[Excerpt] Trade secret information security involves a multi-dimensional array of human, legal, and technological factors. I argue that organizational culture, employee policies, and other human factors are fundamental prerequisites to the successful implementation of legal and technological security measures. After a brief introduction to trade secret law for the nonlegal reader, I present an overview of trade secret litigation and an analysis of computer hacking strategy to emphasize the extent to which the legal and technological dimensions of trade secret information security are predicated on human factors. I conclude with a discussion of how human resource policy can engender cultural sensitivity to trade secrets and mitigate the risk of information leakage

Sometimes the Silence Can Be like the Thunder: Access to Pharmaceutical Data at the FDA

Those committed to the free exchange of scientific information have long complained about various restrictions on access to the FDA\u27s pharmaceutical data and the resultant restrictions on open discourse. A review of open-government procedures and litigation at the FDA demonstrates that the need for transparency at the agency extend well beyond the reach of any clinical trial registry

Adoption and Foster Care by Gay and Lesbian Parents in the United States

Discussion and debate about adoption and foster care by gay, lesbian, and bisexual (GLB) parents occurs frequently among child welfare policymakers, social service agencies, and social workers. They all need better information about GLB adoptive and foster parents and their children as they make individual and policy-level decisions about placement of children with GLB parents. This report provides new information on GLB adoption and foster care from the U.S. Census 2000, the National Survey of Family Growth (2002), and the Adoption and Foster Care Analysis and Reporting System (2004)

Localization of shadow poles by complex scaling

Through numerical examples we show that the complex scaling method is suited to explore the pole structure in multichannel scattering problems. All poles lying on the multisheeted Riemann energy surface, including shadow poles, can be revealed and the Riemann sheets on which they reside can be identified.Comment: 6 pages, Latex with Revtex, 3 figures (not included) available on reques