Page 101 - Encyclopedia of Nursing Research

68 n CLInICAL TRIALS

usually of such magnitude that the results To date, the majority of clinical trials
of non randomized studies are often ambig- have included a limited segment of the U.S.
C uous and not universally accepted unless the population, that is, mainly middle-class,
therapeutic effect is very large. These same married, White males with little to no inclu-
biases are not present to the same degree in sion of women and minorities. This lack of
randomized trials. Recent development and diversity in trial samples has yielded results
use of mega-trials represents one variation. that are not always generalizable and effec-
The mega-trial is a large, simple, ran- tive. Research also has demonstrated bias
domized trial analyzed on an “intent- to- because of subject factors.
treat” basis. In mega-trials randomization Clinical trials are expensive and resource
serves to achieve identical allocation groups intensive. As a result, subject numbers are
(equal distribution of bias), where there generally limited to the minimum number
is poor experimental control and large needed to demonstrate a significant effect not
between- subject variation. Results of mega- caused by chance. However, small clinical tri-
trials cannot readily be generalized because als may not provide convincing evidence of
their conclusions are observations, not causal intervention effects. Small clinical trials are
hypotheses and therefore not testable. Mega- valuable in (a) challenging conventional but
trials can be repeated but not replicated. untested therapeutic wisdom, (b) providing
Mega-trials dispense with the scientific aim data on number of events rather than num-
of maximum experimental control to remove ber of patients and thus may be sufficient to
or minimize bias and instead use randomi- identify the best therapy, and (c) serving as a
zation to achieve equal distribution of bias basis for overview and meta-analysis.
between groups. To deal with the issue of small sample
In clinical drug trials, following approval sizes, meta-analysis is increasingly being
by the Food and Drug Administration, three used. Meta-analysis (quantitative overview) is
phases of clinical trials begin. Phase 1 stud- a systematic review that uses statistical meth-
ies generally establish whether a treatment ods to combine and summarize the results of
is safe and at what dosages. Phase 2 studies several trials. Well-conducted meta-analy-
assess the efficacy of treatments after their ses are the best method of summarizing all
safety and feasibility has been established in available unbiased evidence on the relative
Phase 1. Phase 3 studies compare effective- effects of treatment. In a meta-analysis, the
ness of Phase 2 treatments against currently individual studies are weighted according
accepted treatments. to the inverse of the variance; that is, more
Some scientists divide clinical trials into weight is given to studies with more events.
three groups: (a) exploratory (initial trials Arrangement of the trials according to event
investigating a novel idea), (b) confirmatory rate in the controls, effect sizes, and quality of
(designed to replicate results of exploratory the trials or according to covariables of inter-
trials), and (c) explanatory (designed to mod- est provides unique information. If carried
ify or better understand an established point). out prospectively, the technique provides
Issues surrounding clinical trials include information on the need for another trial, the
biasing, expense of clinical trials, small sam- number of subjects necessary to determine
ple sizes, and ethical issues. There are many the validity of past trends, and the type of
biases that can compromise a clinical trial, subjects who might be benefited.
such as observer bias, interviewer bias, use Ethical issues in clinical trials include
of nonvalidated instruments, uneven subject issues of informed consent, withholding of
recruitment by physicians, and individual treatment, and careful monitoring of clinical
subject factors. Recent concerns have focused trial results. Additional issues of informed con-
on bias in sample selection. sent include assuring that subjects thoroughly