Clinical Trials, Issues,Cost,Ethical Issues and Uniqueness
Whats is Clinical Trial
A clinical trial is a prospective controlled experiment with
patients. There are many types of clinical trials, ranging from studies to
prevent, detect, diagnose, control, and treat health problems to studies of the
psychological impact of a health problem and ways to improve people's health,
comfort, functioning, and quality of life.
Classification of Clinical Trials
The universe of clinical trials is divided differently by different scientists. Clinical trials are often grouped into two major classifications, randomized and nonrandomized studies. A randomized trial is defined as an experiment in which therapies under investigations are allocated by a chance mechanism.
- Randomized clinical trials are comparative experiments that investigate two or more therapies.
- Nonrandomized clinical trials usually involve only one therapy, on which information is collected prospectively and the results compared to historical data.
Comparison
The mega-trial is a large, simple, randomized trial analyzed on an "intent to treat" basis. In mega-trials randomization serves to achieve identical allocation groups (equal distribution of bias) where there is poor experimental control and large between-subject variation.
Results of mega-trials cannot readily be generalized because their conclusions are observations, not causal hypotheses and therefore not testable. Mega trials can be repeated but not replicated.
Mega-trials dispense with the scientific aim of
maximum experimental control to remove or minimize bias and instead use
randomization to achieve equal distribution of bias between groups (Charlton,
1995).
Clinical Trials And FDA
In clinical drug trials, following approval by the Food and Drug Administration (FDA), three phases of clinical trials begin.
Phase I studies generally establish whether a treatment is safe and at what dosages.
Phase II studies assess the efficacy of treatments after their safety and feasibility has been established in Phase I.
Phase III studies compare effectiveness of
Phase II treatments against currently accepted treatments.
Groups or Division of Clinical Trials
Some scientists divide clinical trials into three groups:
(a) exploratory (initial trials investigating a novel idea)
(b) confirmatory (designed to replicate results of exploratory trials)
(c) explanatory (designed to modify or better understand an established points)
Other
scientists divide the universe into two groups, such as pragmatic (practical
benefits to the overall subject population treated) and explanatory ( Viscoli ,
Bruzzi , & Glauser , 1995).
Issues In Clinical Trials
Issues surrounding clinical trials include biasing, expense of clinical trials, small sample sizes, and ethical issues.
There are many biases
that can compromise a clinical trial, such as observer bias, interviewer bias,
use of non validated instruments, uneven subject recruitment by physicians, and
individual subject factors. Recent concerns have focused on bias in sample
selection.
Population And Target Population
To date, the majority of clinical trials have included a limited segment of the US population, that is, mainly middle-class, married, white males with little to no inclusion of women and minorities.
This lack of diversity in trial samples has yielded results that are not always generalizable and effective. Research also has demonstrated bias due to subject factors. For example, subjects were more likely to participate in clinical trials on multiple sclerosis if they had a higher than median income and were disabled from work (Schwartz, CE, & Fox, 1995).
Suggested approaches to reduce selection bias include
(a) using a broad recruitment base to reduce patient and physician biasing factors
(b) facilitating subject transportation to the study site.
Cost or Expense In Clinical Trial
Clinical trials are expensive and resource-intensive. As a result, subject numbers are generally limited to the minimum number needed to demonstrate a significant effect not caused by chance.
However, small clinical trials may not provide convincing evidence of intervention effects. Small clinical trials are valuable in:
(a) challenging conventional but untested therapeutic wisdom
(b) providing data on number of events rather than number of patients and thus may be sufficient to identify the best therapy
(c) serving as a basis for overview and meta-analysis (Sackett & Cook, 1993)
To deal with the issue of small sample sizes, meta-analysis is increasingly being used. Meta-analysis (quantitative overview) is a systematic review that employs statistical methods to combine and summarize the results of several trials.
Well-conducted meta-analyses are the best method of summarizing all available unbiased evidence on the relative effects of treatment (Richards, SM, 1995).
In a meta-analysis the individual studies are weighted according to the inverse of the variance; that is, more weight is given to studies with more events. Arrangement of the trials according to event rate in the controls, effect sizes, and quality of the trials or according to covariables of interest supplies unique information.
If carried out prospectively, the technique provides information on the need for another trial, the number of subjects necessary to determine the validity of past trends and the type of subjects who might be benefited.
Ethical Issues in Clinical Trials
Ethical issues in clinical trials include issues of informed consent, withholding of treatment, and careful monitoring of clinical trial results.
Additional issues of informed consent include assuring that subjects thoroughly understand potential risks and benefits of participation and any effects on their care should they decide to withdraw at any point in the study.
Issues of withholding treatment include increasing subject risk or subject benefit if there is reasonable evidence of positive effects of the intervention or treatment.
Careful monitoring of the effects of interventions or treatment
is necessary to stop the trial if there is associated morbidity or mortality
and extending the intervention or treatment to the control group in the event
of significantly positive treatment effects.
Uniqueness of Clinical Trial In Research
Clinical trials remain the principal way to collect scientific data on the value of interventions and treatment. However, in designing and evaluating clinical trials, rigor of method, including careful evaluation of potential biasing factors, is essential.
Meta-analysis provides a summary of
all available, unbiased evidence on the relative effects of treatment. However,
rigor of methods used to conduct the meta-analysis also must be evaluated.
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