Showing papers by "Michael Hughes published in 1992"

The impact of stopping rules on heterogeneity of results in overviews of clinical trials.

Abstract: This paper explores the extent to which application of statistical stopping rules in clinical trials can create an artificial heterogeneity of treatment effects in overviews (meta-analyses) of related trials. For illustration, we concentrate on overviews of identically designed group sequential trials, using either fixed nominal or O'Brien and Fleming two-sided boundaries. Some analytic results are obtained for two-group designs and simulation studies are otherwise used, with the following overall findings. The use of stopping rules leads to biased estimates of treatment effect so that the assessment of heterogeneity of results in an overview of trials, some of which have used stopping rules, is confounded by this bias. If the true treatment effect being studied is small, as is often the case, then artificial heterogeneity is introduced, thus increasing the Type I error rate in the test of homogeneity. This could lead to erroneous use of a random effects model, producing exaggerated estimates and confidence intervals. However, if the true mean effect is large, then between-trial heterogeneity may be underestimated. When undertaking or interpreting overviews, one should ascertain whether stopping rules have been used (either formally or informally) and should consider whether their use might account for any heterogeneity found.

Prediction of short-term survival with an application in primary biliary cirrhosis.

Abstract: Many long-term follow-up studies for survival accumulate repeated measurements of prognostic factors. Survival models which include only covariate values at baseline do not use all available information, and do not relate to survival predictions for times other than at that baseline. Time-dependent covariate models (which update covariate values as measurements occur through time) might be used, though limitations of software for estimating the underlying hazard functions and difficulty in relating hazard function changes to survival prediction present serious drawbacks. By dividing each patient's follow-up into successive intervals of equal length (using a length of interest for prediction) and with measurements available at the start of each, we describe how an analysis taking person-intervals as the observation units can be undertaken using readily available software to produce short-term survival models. We show that this approach is related to both the baseline and time-dependent covariate models. The method is illustrated using data from a long-term study of patients with primary biliary cirrhosis, where interest is in short-term survival predictions to aid the decision when to undertake liver transplantation.

The Rise and Fall of Pamyat

Abstract: The political liberalisation which took place in the USSR during the late 1980s encouraged the emergence of numerous informal groups (ne/ormal' nyye gruppy), devoted to everything from sport to politics. Many students of Soviet affairs have argued that this development marked the first stage in the emergence of a civil society, which had been crushed by more than 60 years of official repression.' However, while many of the new groups sought to promote and extend the reforms introduced by Gorbachev's perestroika, some of them articulated ideas and values that reflected a more sinister element in the Soviet political culture. The most notorious of these has been the Pamyat' organisation, which came to prominence in the mid-1980s. Pamyat' quickly aroused interest among Soviet and western journalists alike, who wrote reports about its members' penchant for dressing in black shirts and promoting a virulently antisemitic ideology. The group's activities have naturally aroused con­ siderable concern among the former USSR's Jewish population, who fear that the rise of Pamyat' may signify a new chapter in the unsavoury history of Soviet antisemitism. While numerous anti-cosmopolitan campaigns have been directed against Soviet Jews during the past few decades, they have for the most part been firmly controlled and supervised by the regime. By contrast, antisemitism in the former USSR today seems to be taking a more spontaneous form. In the wake of the failed coup against Gorbachev, which at the time of writing seemed to presage a more open and democratic form of government, a new generation of politicians could begin to exploit anti-Jewish sentiment in their search for popular support. Anxiety about such a possibility plays a considerable role in prompting the continuing exodus of Soviet Jews from the former USSR. Although a good deal has been written about the ideas propounded by Pamyat' during the second half of the 1980s, less effort has been made to examine the reasons for the group's impact on Soviet politics. 2 Its rise was largely a consequence of Gorbachev's decision to widen the boundaries of the 'public space' in Soviet life. His attempt to reduce restrictions on the dissemination of information (glasnost') facilitated lateral communications between individuals in Soviet society, which in turn encouraged new forms of social organisation and association. Until recently, almost all these associations have been oriented either to promoting some form of political change (national independence, further liberalisation, etc.), or to bringing together individuals sharing an interest in a particular activity (sport, literature and so forth). Very few of the informal groups have sought to defend the status quo since, at least at first glance, few people outside the old apparat appeared to have many interests or privileges to protect. Pamyat' originated, as will be seen below, as a promotional group that sought to advance the interests of Russian culture and the Russian nation in the face of a supposed attack by the forces of 'cosmopolitanism'