What happened to quinacrine non-surgical female sterilization?

Quinacrine sterilization (QS) is a nonsurgical female method used by more than 175,000 women in over 50 countries. With FDA approval, QS is expected to be used by hundreds of millions of women. The negative international health consequences of the results of a 2-year rat study in 2010 by Cancel et al. in Regulatory Toxicology and Pharmacology (RTP) (56:156-165) are incalculable. S1C(R2) was ignored in this study, including the fundamental concept of maximum tolerated dose (MTD), which resulted in the use of massive doses (up to 35 times the MTD) which killed many of the rats and destroyed the uterus of survivors. The design of this rat study was built on the false assertion that this study mimics what happens in women. Cancel et al. (2010), concludes it "seems most likely" that genotoxicity was a major factor in the carcinogenicity observed, prompting the FDA to halt further research of QS. In RTP, McConnell et al. (2010), and Haseman et al. (2015), using the authors' data, definitively determined the carcinogenicity to be secondary to necrosis and chronic inflammation. Decisions made in the design, conduct, analysis, interpretation and reporting in this study lack scientific foundation. This paper explores these decisions.

A philosophical argument against evidence-based policy.

RATIONALE, AIMS AND OBJECTIVES: Evidence-based medicine has two components. The methodological or ontological component consists of randomized controlled trials and their systematic review. This makes use of a difference-making conception of cause. But there is also a policy component that makes a recommendation for uniform intervention, based on the evidence from randomized controlled trials. METHODS: The policy side of evidence-based medicine is basically a form of rule utilitarianism. But it is then subject to an objection from Smart that rule utilitarianism inevitably collapses. If one assumes (1) you should recommend the intervention that has brought most benefit (the core of evidence-based policy making), (2) individual variation (acknowledged by use of randomization) and (3) no intervention benefits all (contingent but true), then the objection can be brought to bear. CONCLUSIONS: A utility maximizer should always ignore the rule in an individual case where greater benefit can be secured through doing so. In the medical case, this would mean that a clinician who knows that a patient would not benefit from the recommended intervention has good reason to ignore the recommendation. This is indeed the feeling of many clinicians who would like to offer other interventions but for an aversion to breaking clinical guidelines.

Analysis of scientific truth status in controlled rehabilitation trials.

RATIONALE, AIMS AND OBJECTIVES: Systematic reviews, meta-analyses and clinical guidelines (reviews) are intended to inform clinical practice, and in this sense can be thought of as scientific truthmakers. High-quality controlled trials should align to this truth, and method quality markers should predict truth status. We sought to determine in what way controlled trial quality relates to scientific truth, and to determine predictive utility of trial quality and bibliographic markers. METHOD: A sample of reviews in rehabilitation medicine was examined. Two scientific truth dimensions were established based on review outcomes. Quality and bibliographic markers were extracted from associated trials for use in a regression analysis of their predictive utility for trial truth status. Probability analysis was undertaken to examine judgments of future trial truth status. RESULTS: Of the 93 trials included in contemporaneous reviews, overall, n = 45 (48%) were true. Randomization was found more in true trials than false trials in one truth dimension (P = 0.03). Intention-to-treat analysis was close to significant in one truth dimension (P = 0.058), being more commonly used in false trials. There were no other significant differences in quality or bibliographic variables between true and false trials. Regression analysis revealed no significant predictors of trial truth status. Probability analysis reported that the reasonable chance of future trials being true was between 2 and 5%, based on a uniform prior. CONCLUSIONS: The findings are at odds with what is considered gold-standard research methods, but in line with previous reports. Further work should focus on scientific dynamics within healthcare research and evidence-based practice constructs.

Causation and evidence-based practice: an ontological review.

This paper explores the nature of causation within the framework of evidence-based practice (EBP) for health care. The aims of the paper were first to define and evaluate how causation is presently accounted for in EBP; second, to present an alternative causal account by which health care can develop in both its clinical application and its scientific research activity. The paper was premised on the idea that causation underlies medical and health care practices and impacts on the way we understand health science research and daily clinical practice. The question of what causation is should therefore be of utmost relevance for all concerned with the science, philosophy and progress of EBP. We propose that the way causation is thought of in contemporaneous health care is exposed by evidential frameworks, which categorize research methods on their epistemological strengths. It is then suggested that the current account of causation is limited in respect of both the functionality of EBP, and its inherent scientific processes. An alternative ontology of causation is provided, which has its roots in dispositionalism. Here, causes are not seen as regular events necessitating an effect, but rather phenomena that are highly complex, context-sensitive and that tend towards an effect. We see this as a better account of causation for evidence-based health care.