Active‐controlled,non‐inferiority trials in oncology: arbitrary limits,infeasible sample sizes and uninformative data analysis. Is there another way?

In oncology, it may not always be possible to evaluate the efficacy of new medicines in placebo-controlled trials. Furthermore, while some newer, biologically targeted anti-cancer treatments may be expected to deliver therapeutic benefit in terms of better tolerability or improved symptom control, they may not always be expected to provide increased efficacy relative to existing therapies. This naturally leads to the use of active-control, non-inferiority trials to evaluate such treatments. In recent evaluations of anti-cancer treatments, the non-inferiority margin has often been defined in terms of demonstrating that at least 50% of the active control effect has been retained by the new drug using methods such as those described by Rothmann et al., Statistics in Medicine 2003; 22:239-264 and Wang and Hung Controlled Clinical Trials 2003; 24:147-155. However, this approach can lead to prohibitively large clinical trials and results in a tendency to dichotomize trial outcome as either 'success' or 'failure' and thus oversimplifies interpretation. With relatively modest modification, these methods can be used to define a stepwise approach to design and analysis. In the first design step, the trial is sized to show indirectly that the new drug would have beaten placebo; in the second analysis step, the probability that the new drug is superior to placebo is assessed and, if sufficiently high in the third and final step, the relative efficacy of the new drug to control is assessed on a continuum of effect retention via an 'effect retention likelihood plot'. This stepwise approach is likely to provide a more complete assessment of relative efficacy so that the value of new treatments can be better judged.     

Book Review Guns,Germs and Steel: The Fates of Human Societies. Jared Diamond. New York: W.W. Norton, 1997, 480 pp.

Population and Environment -     

Elimination ofSitotroga cerealella (Olivier) bySitophilus zeamais Motschulsky from mixed laboratory cultures on maize

Summary This paper describes a series of experiments conducted to determine whySitophilus zeamais Mots. andSitotroga cerealella (Oliv.) could not survive together in maize cultures in the laboratory. The effect ofS. zeamais on different developmental stages ofS. cerealella was investigated. The presence of adultS. zeamais slightly affected moth copulation, egg laying and moth eggs in a mixed culture, but large numbers of developing moths inside maize grains were killed by the adult weevil through feeding on the grains. The major cause of elimination ofS. cerealella byS. zeamais from mixed cultures was therefore found to be damage to the immature moths in grain and such moth mortality increased as the developing moths became bigger in the grains. A weevil: grain ratio of approximately 1.4∶1 was found to be the critical weevil density at which the moth disappeared from the mixed cultures.     

Theory Trimming

This paper attempts to show that the “Theory Trimming” technique makes little contribution to theory in sociology. A brief history of the technique is given, and several key assertions of its proponents are abstracted. These assertions are shown to be highly questionable. The general alternative to Theory Trimming is shown, and the relationship between Theory Trimming and more general orientations to research is discussed.     

The measurement of diversity: Ethnic and socioeconomic mixing in residential areas

Units of observation such as census tracts continue to be analyzed according to various modal characteristics while the variation or diversity existent in such units is often ignored. The qualitative or nominal-level indicators of diversity are examined which (1) are operative in the polytomous situation, and (2) measure within-unit diversity rather than divergences among units. Six qualitative indicators are explained and compared both theoretically and by example, with the Index of Qualitative Variation suggested as the most appropriate measure of diversity when variables representing a nominal scale are used. Quantitative or interval-level diversity also was examined with six measures analyzed, representing three operational situations. Because of the susceptibilities of five of the quantitative measures to skewness and variable sample sizes, the coefficient of variation was recommended for interval-level variables to evaluate within-unit diversity.     

Medical Students' Attitudes and Opinions About Human Sexual Behaviour

In their professional capacities doctors are often confronted with clients who present with psycho-sexual problems. At the present time Australian medical students are provided with very little instruction in the areas of human sexual behaviour. This paper examines the attitudes and amount of information possessed by a cohort of second year medical students compared with groups of first and fifth year students; these attitudes and levels of information are then related to students' sex, religious affiliation, strength of religious conviction, where this is seen to be relevant. It is shown that some areas of ignorance exist. The paper concludes by outlining some aspects relevant to courses in human sexual behaviour.