Negative and non-positive epidemiological studies

Abstract. The aim of this study was to identify and discuss validity aspects on so called negative and non-positive studies. Arguments and examples are drawn from experiences in occupational health epidemiology regarding the interpretation of more or less equivocal study results. A negative study may be defined as showing a result that goes against the investigated hypothesis of an increased (or prevented) risk. Traditionally, studies with a risk estimate (relative risk or odds ratio) above, but close to unity are also referred to as negative, given a narrow confidence interval (CI) that includes unity. A risk estimate above unity with the CI including unity is non-positive, however, but an estimate below unity with upper CI bond exceeding unity might be seen as possibly negative or non-negative. A weaker "significance" than usually required should perhaps be accepted when evaluating serious hazards. In contrast to positive studies, the negative and non-positive studies tend to escape criticism in spite of questionable validity that may have obscured existing risks (or preventive effects). Even stronger arguments can be made in criticising negative and non-positive studies than positive studies, for example, regarding selection phenomena, and observational problems regarding exposure and outcome. Negative confounding should be considered although usually weak. In case-control studies, so called over-matching may obscure an existing risk as could the "healthy worker effect" in cohort studies. Small scale non-positive studies should be made available for metaanalyses and when considering studies that do not convincingly show a risk; those who are exposed should be given the "benefit of the doubt"

Agent orange in war medicine : An aftermath myth

Since the late 1970s several epidemiological studies have appeared linking exposure to phenoxy herbicides or chlorophenols to some malignant tumors. Most of these compounds are contaminated with dioxins and dibenzofurans; for example, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a contaminant of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a component of Agent Orange which was sprayed in Vietnam during the war. The results of some of the epidemiological studies on cancer risks associated with exposure to these compounds have been manipulated and misinterpreted, particularly by the Australian Royal Commission on the Use and Effects of Chemical Agents on Australian Personnel in Vietnam. Furthermore, a book on Australian war history entitled Medicine at War, commissioned by the Federal Government, reiterates several of these misinterpretations, despite available contrary evaluations from Australian and U.S. authorities. These remarkable and confusing circumstances in the scientific process are considered also in the light of the recent classification of TCDD as carcinogenic to humans, Group 1, by a Working Group at the International Agency for Research on Cancer in Lyon, France