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Clinical Trials 101

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Every year, thousands of physicians participate in their first clinical trial. This is not only an educational experience, but also a humbling one. A clinical trial is an experiment performed on humans to compare the efficacy of two or more therapeutic options. The multi-center, randomized, masked, controlled trial is the gold standard of clinical research and produces the most reliable comparison of treatment modalities. Another essential aspect of a well-designed clinical trial is the random allocation of subjects to the experimental and control groups.

Prior to agreeing to participate in a clinical trial, the principal investigator needs to critically evaluate the protocol to determine that the trial is both well-designed and ethical. The principal investigator should also make sure that the benefits of participating in the trial outweigh the risks1–5.

It typically takes about 10 years for the discovery of a new medication to reach FDA approval. During this period, preclinical studies and various phases of clinical trials will be performed. Less than 1 percent of screened compounds progress to a clinical trial and less than 1 in 1,000 compounds gain final FDA approval1.

Phases of Clinical Trials
There are four phases for clinical trials2,3:

  • Phase I: A phase I trial is the first use of a drug in humans and usually involves a small number of subjects (i.e., 10 to 20). The purpose of a phase I trial is to investigate the pharmacokinetics, pharmacodynamics and toxicity of the drug.
  • Phase II: A phase II study is conducted on a medium number of patients (i.e., 100 to 200). The purpose of a phase II trial is to study optimal drug dose, safety and efficacy.
  • Phase III: A phase III trial is a major investigation involving hundreds or thousands of patients. The purpose of a phase III trial is to conclusively demonstrate both the safety and efficacy of the drug in question and to provide a comparison of the drug to the accepted standard of care.
  • Phase IV: A phase IV trial is a study carried out after registration of the drug. The purpose of a phase IV trial is to evaluate the drug’s long-term safety and efficacy, as well as new indications.

Good Clinical Practice
Good clinical practice defines the standards for conducting clinical research and clinical trials. This guideline applies to all aspects of a clinical trial, including design, patient recruitment, monitoring, recording, analysis and reporting the results3.

The main aspects of good clinical practice include protection of the subjects and reliable and correct data.

Regulatory Authorities
Regulatory agencies oversee the conduct of clinical trials. These agencies include the FDA in the United States, the Health Protection Branch in Canada, the Ministry of Health and Welfare in Japan and the Committee for Proprietary Medicinal Products in the European Union.

In the United States, clinical trials can be registered online at Registration of a clinical trial is a requirement for presentation of results at meetings of the Association for Research in Vision and Ophthalmology and other major meetings.

Responsibilities of a Principal Investigator
Principal investigators are responsible for the ethical and accurate conduct of a clinical trial. The responsibilities of a principal investigator include1,4:

  • Conducting or supervising the study according to the protocol;
  • Obtaining institutional review board (IRB) approval;
  • Obtaining informed consent, which includes informing subjects about possible downsides of participation in the trial;
  • Reporting adverse events to the sponsor and IRB; and
  • Maintaining accurate records.

Institutional Review Board
The IRB, which can also be known as the human investigation committee or ethics committee, protects the rights and welfare of the study participants. The IRB has the responsibility to review and approve the protocol and oversee the conduct of the study4. IRB approval may take a few months.

There are two types of IRBs: central IRB, such as the Western IRB, and institutional IRB, such as university or hospital IRBs.

Informed Consent
The process of obtaining informed consent includes providing unbiased information to the subject. The patient must be informed not only about the advantages of participating in the trial, but the risks and alternatives as well. An important aspect of clinical trials is the voluntary participation of subjects2,3.

Study Coordinator
The study coordinator is a research professional who helps conduct a clinical trial. The study coordinator does the bulk of the daily activities for most of the clinical trials. Usually a study coordinator is a trained nurse or technician. They often have multiple duties, including patient care, administration, business aspects and data processing. Thus, the study coordinator should be well-organized and capable of multitasking1.

Conducting clinical trials is a rewarding experience. Principal investigators usually enjoy practicing cutting-edge medicine and advancing clinical knowledge. Subjects may benefit from a new, though untested, treatment. Well-designed, randomized clinical trials provide the highest quality clinical data that lead to improved understanding of treatment options. Most importantly, the results of clinical trials impact practice of medicine and may help a large number of future patients.

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About the author: Ron A. Adelman, MD, MPH, FACS, is an associate professor of ophthalmology at Yale University School of Medicine. He would like to thank Xuejing Chen for editing the text.

1Ginsberg D. 2005. Becoming a successful clinical research investigator. Thomson Centerwatch, Boston, MA.

2Machin D, Day S, Green S. 2004. Textbook of clinical trials. John Weily & Sons, West Sussex, UK.

3Kolman J, Meng P. 1998. Good clinical practice. John Weily & Sons, West Sussex, UK.

4Liu MB, Davis K. 2001. Lessons from a horse named Jim:  A clinical trial manual from the Duke Clinical Research Institute. Duke Clinical Research Institute, Durham, NC.

5Anderson DL. 2004. A guide to patient recruitment and retention. Thomson Centerwatch, Boston, MA.