36 research outputs found

    The fallacy of enrolling only high-risk subjects in cancer prevention trials: Is there a "free lunch"?

    Get PDF
    BACKGROUND: There is a common belief that most cancer prevention trials should be restricted to high-risk subjects in order to increase statistical power. This strategy is appropriate if the ultimate target population is subjects at the same high-risk. However if the target population is the general population, three assumptions may underlie the decision to enroll high-risk subject instead of average-risk subjects from the general population: higher statistical power for the same sample size, lower costs for the same power and type I error, and a correct ratio of benefits to harms. We critically investigate the plausibility of these assumptions. METHODS: We considered each assumption in the context of a simple example. We investigated statistical power for fixed sample size when the investigators assume that relative risk is invariant over risk group, but when, in reality, risk difference is invariant over risk groups. We investigated possible costs when a trial of high-risk subjects has the same power and type I error as a larger trial of average-risk subjects from the general population. We investigated the ratios of benefit to harms when extrapolating from high-risk to average-risk subjects. RESULTS: Appearances here are misleading. First, the increase in statistical power with a trial of high-risk subjects rather than the same number of average-risk subjects from the general population assumes that the relative risk is the same for high-risk and average-risk subjects. However, if the absolute risk difference rather than the relative risk were the same, the power can be less with the high-risk subjects. In the analysis of data from a cancer prevention trial, we found that invariance of absolute risk difference over risk groups was nearly as plausible as invariance of relative risk over risk groups. Therefore a priori assumptions of constant relative risk across risk groups are not robust, limiting extrapolation of estimates of benefit to the general population. Second, a trial of high-risk subjects may cost more than a larger trial of average risk subjects with the same power and type I error because of additional recruitment and diagnostic testing to identify high-risk subjects. Third, the ratio of benefits to harms may be more favorable in high-risk persons than in average-risk persons in the general population, which means that extrapolating this ratio to the general population would be misleading. Thus there is no free lunch when using a trial of high-risk subjects to extrapolate results to the general population. CONCLUSION: Unless the intervention is targeted to only high-risk subjects, cancer prevention trials should be implemented in the general population

    Tumour microvessel density as predictor of chemotherapy response in breast cancer patients

    Get PDF
    The aim of this study was to evaluate the predictive value of intratumoural microvessel density in breast cancer. We studied immunohistochemically primary tumours of 104 patients with metastasised breast cancer who took part in a randomised multicentre trial comparing docetaxel to sequential methotrexate and 5-fluorouracil. Vessels were highlighted with factor VIII staining and counted microscopically. Microvessel density was compared with clinical response to chemotherapy and patient survival. The microvessel density of the primary tumour was not significantly associated with patient's response to chemotherapy, time to progression or overall survival in the whole patient population or in the docetaxel or methotrexate and 5-fluorouracil groups. However, disease-free survival was longer in patients with low microvessel density (P=0.01). These findings suggest that microvessel density of the primary tumour cannot be used as a predictive marker for chemotherapy response in advanced breast cancer

    Confocal scanning optical microscopy and related imaging systems

    No full text
    Includes bibliographical references and index

    Complete degradation of dimethyl isophthalate requires the biochemical cooperation between Klebsiella oxytoca Sc and Methylobacterium mesophilicum Sr Isolated from Wetland sediment

    Get PDF
    Two bacterial strains Klebsiella oxytoca Sc and Methylobacterium mesophilicum Sr were isolated and identified from enrichment cultures using dimethyl isophthalate (DMI) as the sole source of carbon and energy, and mangrove sediment as an inoculum. DMI was rapidly transformed by K. oxytoca Sc in the culture with formation of monomethyl isophthalate (MMI), which accumulated in the culture medium. M. mesophilicum Sr, incapable of utilizing DMI, showed high capability of degrading MMI to a transitory intermediate isophthalic acid (IPA), which was further mineralized by this strain. The biochemical pathway of DMI degradation by these two bacteria in a consortium was proposed: DMI to MMI by K. oxytoca Sc, MMI to IPA by M. mesophilicum Sr, and IPA by both K. oxytoca Sc and M. mesophilicum Sr based on the identified degradation intermediates. The consortium comprising K. oxytoca Sc and M. mesophilicum Sr was effective in mineralization of DMI. The results suggest that complete degradation of environmental pollutant DMI requires the biochemical cooperation between different microorganisms of the mangrove environment. © 2006 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex

    Analysis of combined data from heterogeneous study designs: an applied example from the patient navigation research program.

    No full text
    Background The Patient Navigation Research Program (PNRP) is a cooperative effort of nine research projects, with similar clinical criteria but with different study designs. To evaluate projects such as PNRP, it is desirable to perform a pooled analysis to increase power relative to the individual projects. There is no agreed-upon prospective methodology, however, for analyzing combined data arising from different study designs. Expert opinions were thus solicited from the members of the PNRP Design and Analysis Committee. Purpose To review possible methodologies for analyzing combined data arising from heterogeneous study designs. Methods The Design and Analysis Committee critically reviewed the pros and cons of five potential methods for analyzing combined PNRP project data. The conclusions were based on simple consensus. The five approaches reviewed included the following: (1) analyzing and reporting each project separately, (2) combining data from all projects and performing an individual-level analysis, (3) pooling data from projects having similar study designs, (4) analyzing pooled data using a prospective meta-analytic technique, and (5) analyzing pooled data utilizing a novel simulated group-randomized design. Results Methodologies varied in their ability to incorporate data from all PNRP projects, to appropriately account for differing study designs, and to accommodate differing project sample sizes. Limitations The conclusions reached were based on expert opinion and not derived from actual analyses performed. Conclusions The ability to analyze pooled data arising from differing study designs may provide pertinent information to inform programmatic, budgetary, and policy perspectives. Multisite community-based research may not lend itself well to the more stringent explanatory and pragmatic standards of a randomized controlled trial design. Given our growing interest in community-based population research, the challenges inherent in the analysis of heterogeneous study design are likely to become more salient. Discussion of the analytic issues faced by the PNRP and the methodological approaches we considered may be of value to other prospective community-based research programs. </jats:p
    corecore