Clinical Research

Clinical research is the process by which a new drug or therapeutic modality is introduced into common clinical practice. A clinical trial has three distinct phases or subtypes. Using a new drug as an example, a Phase I trial is the first exposure of a drug or intervention in a human. Frequently researchers have experimented on animals to determine an approximate dose range and potential adverse effects. However, because of differences between humans and other animals, dose range, absorption, excretion, side effects, metabolism, and efficacy must be investigated. Phase I trials are frequently of small size and involve a large amount of data collection, because researchers may find unexpected or unexplained responses or effects in humans. Most drugs that reach a Phase I trial move to a Phase II trial, which is frequently larger in scope, enrolls more participants and further investigates the dose range and efficacy of the drug compared with existing treatments. Potential side effects discovered in the Phase I trial are further investigated and potentially managed. If the results of a Phase II trial show a new drug is effective, then investigations proceed to a Phase III trial. The purpose of this series of investigations is to determine how the new treatment compares with existing modalities. Occasionally, two experimental treatments are directly compared with one another. Phase III trials often require a large number of participants to detect subtle differences that may exist between the new and existing treatments. Frequently these studies involve more than one medical center, to obtain a sufficient sample [Page 77]size in a timely fashion. During both Phase II and Phase III trials, participants are often randomized to either the new treatment or an existing treatment without the knowledge of the clinicians directly treating the patients. This is done to minimize potential participant and investigator biases. (See entry for Blinding.) The individuals receiving the new treatment are the experimental group and the individuals receiving the standard modality are the control group. A Phase III trial may also be used to compare different dosing schedules or regiments of pre-existing modalities, to determine which is most efficacious. An additional Phase IV may be added as a postapproval and marketing study to further investigate the side effects and efficacy of a drug.

Whenever human research is conducted, all experimental protocols must be reviewed by a committee known commonly as an institutional review board (IRB). The IRB is frequently composed of physicians and other health care professionals, lawyers, researchers, and members of the community. The responsibilities of the IRB are to ensure that the researcher is qualified to conduct the study, to determine if the trial is well planned, and to ensure that patient recruitment, enrollment, confidentiality, and compensation are appropriate. As any human study requires informed consent, the IRB is also responsible for ensuring that the information given to patients is complete and in an easily understandable format. Throughout the duration of the study, the investigator and IRB must remain in communication with regard to unexpected side effects and adverse events. The IRB also has the ability to postpone or terminate a study if it is felt the potential risks to the participants involved outweigh the potential benefits. The study may also be closed prematurely based on the data collected. As the study is ongoing, the preliminary data may show that the new drug or treatment modality is not as efficacious as initially proposed, or even potentially harmful, showing side effects not seen during Phase I and II trials. It is therefore unethical to continue to expose participants to increased risk. Likewise, if the new treatment is shown to be significantly better than the standard treatment, the ongoing trial can be halted and all patients could then receive the newer, more efficacious treatment.

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