Research Facts: Clinical Trials 2004 Edition

The growing concern over the financing of health care has resulted in payers asking clinicians for evidence-based practice data to support use of a given treatment. Furthermore, the data being sought are usually based upon the results of a randomized clinical trial. Yet this form of experiment is not often used in the discipline of communication sciences and disorders. If the discipline is to move towards evidence-based practice, then clinical trials are the vehicles which both researchers and clinicians must become familiar with. This Research Facts addresses basic questions concerning clinical trials and their employment in communication sciences and disorders.

Glossary

• Effectiveness : A measure of the extent to which a specific intervention, procedure, regimen, or service, when deployed in the field in routine circumstances, does what it is intended to do for a specified population (1).
• Efficacy : The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal circumstances (1).
• Protocol : The plan, or set of steps, to be followed in a study or investigation, or in an intervention program (1).
• Randomization/Randomized Clinical Trial : An epidemiological experiment in which subjects in a population are randomly allocated into groups, to receive or not to receive an experimental preventive or therapeutic procedure, maneuver, or intervention (1).

The clinical trial: What is it?

A clinical trial is a planned experiment designed to assess the efficacy of treatment in individuals by comparing the outcomes in a group of patients treated with the test treatment with those observed in a comparable group receiving a control treatment, where patients in both groups are enrolled, treated, and followed over the same period of time (2).

Though the importance of clinical trials relative to the introduction of new drugs and treatment is fairly recent, the modern use of clinical trials can be traced to the 1600s. The East India Company sent four ships from Europe, only one ship of which contained a supply of lemon juice. The sailors on the ship carrying the juice remained free of scurvy (2).

Modern clinical trials are more complicated to conduct than the study mentioned above. Ideas for clinical trials primarily originate from scientists who are experts in the area of the medical condition targeted for the study. Once researchers test new therapies or procedures in the laboratory and promising results are obtained, planning commences in designing the trial project. Clinical trials are divided into the following four phases:

• Phase I tests a new drug or treatment on a small group of individuals (approximately 20-80) for the first time to evaluate its elemental safety, to determine a safe dosage range, and to identify side effects.
• Phase II trials examine the treatment in a larger group (100-300 individuals) to further assess safety and effectiveness. Subjects tend to be randomly allocated to study and control groups.
• In Phase III , the test treatment is given to larger groups (1,000-3,000 persons) to confirm its effectiveness and monitor side effects, to compare it to commonly used treatments, and to collect information that will allow the regimen to be used safely (3). Phase III trials serve to validate the results of Phase I and Phase II trials because more is known about the treatment (4).
• Phase IV studies are conducted after the treatment has been marketed. These studies continue the testing in order to collect information about the regimen's effect in various populations, as well as any side effects associated with long-term use (3). Ethical review is required for Phase IV trials, but not for routine post-marketing surveillance (2).

No clinical trial is an entity unto itself. Each trial should be considered as part of an evolving research program. Confirmatory studies are essential for all clinical trials. If beneficial results are observed in a particular trial, they will not gain acceptance unless they can be repeated by other investigators who treat the same types of patients in a similar manner (5).

Why are clinical trials important?

There are several reasons why clinical trials, in and of themselves, are important in the field of science. The first is that the trials' findings contribute to the knowledge base in understanding the cause, development, progression, and possible treatment of a disease or condition. The trials may also answer important scientific questions and suggest areas needing further research (6). The second reason why clinical trials are performed is related to the understanding of how a particular condition progresses. Advancement is made in the area of treatment as a result of new ideas developed through research. These new approaches must be proven safe and effective in scientific studies before they may be made widely available.

In relation to communication disorders, these reasons are reflected in the overall importance of experimental-clinical research. To begin, such work is essential in generating basic knowledge about the acquisition, production, and maintenance of various aspects of communication. It is necessary to know the neurophysiological, genetic, environmental, and other factors that are functionally involved in the processes of speech, language, and hearing. The experimental method can produce more definitive evidence on the independent variables that may be responsible for normal communicative behaviors. The experimental method is also essential in gaining an understanding of the factors that lead to various types of disordered communication. The method can isolate the factors involved in the production of disordered communication. Lastly, experimental research is essential in evaluating the effects of various treatment programs designed to remediate disorders of communication. Treatment, by definition, is designed to change a clinical condition (7). In short, clinical trials are the media for progress in the habilitative and rehabilitative sciences.

Where are clinical trials conducted?

Clinical trials may be performed at various medical or educational facilities, depending on the type of trial being conducted. Participants may receive treatment at a medical center, university hospital, community clinic, or physician's office.

In 1997, the National Institute on Deafness and Other Communication Disorders funded the first cooperative group, the Communication Sciences and Disorders Clinical Trials Research Group (CSDRG), devoted solely to trials in communication disorders by speech-language and hearing scientists and clinicians. For more information about the CSDRG, please e-mail ASHA at research@asha.org.

How is a clinical trial conducted?

When trials are being carried out, there are two primary foci: the well-being of the patient and the research concerns. In this, it is essential that strict adherence to trial guidelines, as well as ethical guidelines, be maintained.

Once the protocol is developed, and before the trial begins, a review and approval by the Institutional Review Board (IRB) is required. Every hospital, clinic, or medical school that conducts clinical trials has its own IRB or contracts with some other entity to use its IRB. The review board members include doctors, nurses, social workers, ethics experts, and others.

The investigator must provide the following information to the IRB for each clinical trial:

• protocol
• consent form and process
• investigator's brochure
• number and description of research subjects
• review of known risks and benefits
• any other information the IRB may request

The investigator must also submit annual reports to the IRB on the clinical trial. Based upon these reports, the Board may approve the continuation of the study, suspend the study, or terminate it.

Most funding agencies use a Data and Safety Monitoring Committee (DSMC) to assure patient participant safety and the integrity of the study. One of the most important functions of the Committee is to review all adverse events. The DSMC can suspend or terminate the study if it finds evidence of a potential significant problem (4).

References

1. Last, J.M. (1995). A dictionary of epidemiology (3 ^rd ed.). New York: Oxford University Press.

2. Meinert, C.L. (1986). Clinical trials: Design, conduct, and analysis. New York: Oxford University Press.

3. National Institutes of Health (2003, June 30). An introduction to clinical trials<Accessed November 14, 2003, http://clinicaltrials.gov/ct/info/whatis>.

4. Giffels, J.J. (1996). Clinical trials: What you should know before volunteering to be a research subject. New York: Demos Vermande.

5. Gehan, E.A., & Lemak, N.A. (1994). Statistics in medical research: Developments in clinical trials. New York: Plenum Medical Book Co.

6. National Cancer Institute. (N.D.). Taking part in clinical trials: What cancer patients need to know (Pub. No. 98-4250). Bethesda, MD: Author.

7. Hegde, M.N. (1994). Clinical research in communicative disorders: Principles and strategies (2 ^nd ed.). Austin, TX: Pro-Ed.

Compiled by Andrea Castrogiovanni * American Speech-Language-Hearing Association * 2200 Research Boulevard, Rockville, Maryland 20850 * acastrogiovanni@asha.org