of the drug/treatment. Formal approval of a new drug or biomedical procedure generally cannot be made until a phase III trial is completed and there is strong evidence that the drug/treatment is safe and effective.
The purpose of a phase I clinical trial is to investigate the safety, efficacy, and side effects of a new drug or treatment. Phase I trials usually involve a small number of subjects and take place at a single or only a few different locations. In a drug trial, the goal of a phase I trial is often to investigate the metabolic and pharmacologic actions of the drug, the efficacy of the drug, and the side effects associated with different dosages of the drug. Phase I drug trials are also referred to as dose finding trials.
When the results of a phase I trial suggest that a treatment or drug appears to have promise, the treatment or drug is generally next studied in a phase II trial. In phase II clinical trials, the drug or treatment being studied is evaluated on a larger group of subjects to further investigate its effectiveness and safety. In general, the goal of a phase II trial is to study the feasibility and level of activity of the drug or treatment. Thus, phase II trials are designed to provide more information about the effective dosage of a drug, the severity of the side effects, and how to manage the side effects. Phase II trials are also referred to as safety and efficacy trials and usually involve more subjects than phase I trials.
When the preliminary results of a new drug or treatment from a phase II trial suggest the drug or treatment will be effective and safe, a phase III trial is designed to gather additional information that can be used in evaluating the overall benefit–risk relationship of the drug. Phase III trials are usually designed to compare the new drug/treatment with standard or commonly used drugs/treatments, to confirm its effectiveness, to further monitor side effects, and to determine how the new drug or treatment can be safely used. Phase III trials generally are large trials and may enroll subjects at a wide variety of locations. Phase III trials are also referred to as comparative treatment efficacy trials.
Finally, when a new drug or treatment has been examined in phase I, II, and III trials and has been approved for the general public, a phase IV trial is usually initiated. A phase IV trial is a postmarketing study designed to obtain additional information on the risks associated with the drug/treatment, its benefits, and its optimal use. The primary aim of a phase IV trial is to evaluate the long-term safety and effectiveness of a drug/treatment. Phase IV trials sometimes result in a drug being taken completely off the market or new restrictions being placed on the use of the drug. Phase IV trials are also referred to as expanded safety trials and usually involve a very large number of subjects.
Note that the number of subjects in a trial usually increases as the phases of the study progress. That is, a phase I trial usually involves fewer subjects than a phase II trial, a phase II trial usually involves fewer subjects than a phase III trial, and a phase III trial usually involves fewer subjects than a phase IV trial. Also, some research studies involving human subjects will have less than four phases. For example, it is not unusual for screening, prevention, diagnostic, genetic, and quality-of-life studies to be conducted in only phase I or II trials. However, new drugs and biomedical procedures almost always require phase I, II, and III clinical trials for approval and a phase IV trial to track the safety of the drug after its approval. The development of a new drug may take many years to proceed through the first three phases of the approval process, and following approval, the phase IV trial usually extends over a period of many years.
1.4 Data Set Descriptions
Throughout this book several data sets will be used in the examples and exercises. These data sets are available at www.mtech.edu/math/faculty/rick-rossi/Book-Rossi.html as Excel files and MINITAB worksheets; web addresses frequently change at Montana Tech, searching for Rick Rossi on the Montana Tech web page will also allow you to find the data sets on my personal web page.
Permission to use the Birth Weight, Intensive Care Unit, Coronary Heart Disease, UMASS Aids Research Unit, and Prostate Cancer data sets has been granted by John Wiley & Sons, Inc. These data sets were first published in Applied Logistic Regression (Hosmer, 2000). Permission to use the Body Fat data set has been provided by Roger W. Johnson, Department of Mathematics & Computer Science, South Dakota School of Mines & Technology and the Journal of Statistics Education.
1.4.1 Birth Weight Data Set
The Birth Weight data set consists of data collected on 189 women to identify the risk factors associated with the birth of a low birth weight baby. The data set was collected at the Baystate Medical Center in Springfield, Massachusetts. The variables included in this data set are summarized in Table 1.1.
Table 1.1 A Description of the Variables in the Birth Weight Data Set
| Variable | Description | Codes/Values | Name |
|---|---|---|---|
| 1 | Identification code | ID number | ID |
| 2 | Low birth weight | 1 = BWT≤2500 g | LOW |
| 0 = BWT>2500 g | |||
| 3 | Age of mother | Years | AGE |
| 4 | Weight of mother at | Pounds | LWT |
| last menstrual period | |||
| 5 | Race | 1 = White | RACE |
| 2 = Black | |||
| 3 = Other | |||
| 6 | Smoking status during pregnancy | 0 = No | SMOKE |
| 1 = Yes | |||
| 7 | History of premature labor | 0 = None | PTL |
| 1 = One | |||
| 2 = Two, etc. | |||
| 8 | History of hypertension | 0 = No |
HT
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