Implementation Of Randomization

In the pharmaceutical industry, for good clinical practice a set of standard operating procedures (SOP) for generation, implementation, and administration of randomization is usually established to ensure the integrity of clinical trials. In this section we will introduce an implementation procedure for the method of nonadaptive randomizations which is adopted by most of pharmaceutical companies for clinical research and development. In the pharmaceutical industry the department of...

Tacrine Enrichmnet Design

Figure 5.6.1 An enrichment design for tacrine in patients with probable Alzheimer's disease. (Source Davis et al., 1992.) which were conducted in double-blind fashion. The potentially therapeutic response for each patient at each dose were then assessed at the end of each two-week dosing period. The best dose response for a patient was defined in advance in the protocol as a reduction of at least four points from the screening value in a total score on the Alzheimer's disease assessment scale...

MedDRA

As mentioned above, currently there is no uniform definition for adverse events. As a result, no internationally accepted medical terminology exists for evaluation of safety information for regulatory purpose. However, most pharmaceutical companies as well as regulatory agencies employ one of the international adverse drug reaction terminologies in combination with morbidity terminology. For example, regulatory agencies in Europe use a combination of WHOART and ICD-9th Revision (ICD-9). The...

Baseline Comparison

Baseline measurements are those collected during the baseline periods as defined in the study protocol. Baseline usually refers to as measurements obtained at randomization and prior to treatment. Sometimes, measurements obtained at screening are used as baselines. Also, baselines are not always restricted to pretreatment measurements. For example, for complicated designs such as the enrichment design for the assessment of Tacrine in the treatment of Alzheimer's disease and CAST for arrhythmia,...

Target Population And Patient Selection

As was indicated earlier, one of the primary objectives of a clinical trial is to provide an accurate and reliable clinical evaluation of a study drug for a target patient population with certain diseases. In practice, statistical and clinical inference are usually drawn based on a representative sample (a group of patients to be enrolled in the trial) selected from the target patient population of the clinical trial. A representative sample provides the clinician with the ability to generalize...

Database Development

Edit Check Clinical Trial

As indicated by Grobler et al. (2001), a database should be designed to facilitate data entry and the extraction of data for analysis. Database development includes database design (or setup) and database edit check specifications, which are briefly outlined below. In practice, for a given clinical trial, to facilitate data entry and the extraction of data for analysis, a protocol-specific database is set up using standard templates (e.g., modules and format libraries or data dictionaries)...

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Figure 12.4.1 Adjustment for covariate in estimation of treatment effect. Case I Common slope. Figure 12.4.2 Adjustment for covariate in estimation of treatment effect. Case II Different slopes, same direction but different magnitude. Figure 12.4.2 Adjustment for covariate in estimation of treatment effect. Case II Different slopes, same direction but different magnitude. estimate the common treatment effect over the entire range of the covariate. Figure 12.4.2 depicts a situation where the...

Descriptive And Inferential Statistics

Dietrich and Kearns (1986) divided statistics into two broad areas, namely descriptive and inferential statistics. Descriptive statistics is the science of summarizing or describing data, while inferential statistics is the science of interpreting data in order to make estimates, hypotheses testing, predictions, or decisions from the samples to the targeted population. In clinical trials, data are usually collected through case report forms which are designed to capture clinical information...

Bias And Variability

As was indicated earlier, the FDA requires that the results from clinical trials be accurate and reliable in order to provide a valid and unbiased assessment of true efficacy and safety of the study medication. The accuracy and reliability are usually referred to as the closeness and the degree of the closeness of the clinical results to the true value regarding the targeted patient population. The accuracy and reliability can be assessed by the bias and variability of the primary clinical...

Multicenter Trial

When conducting a clinical trial, it may be desirable to have the study done at a single study site if (1) the study site can provide an adequate number of relatively homogeneous patients that represent the targeted patient population under study and (2) the study site has sufficient capacity, resources, and supporting staff to sponsor the study. One of the advantages for a single-site study is that it provides consistent assessment for efficacy and safety in a similar medical environment. As a...

Risk of Exposure

In clinical trials the toxicity or risk of exposure to a drug can generally described as a function of the exposure to the drug where the exposure to the drug depends on the dose and time of exposure. If we assume a constant dose, then the toxicity is a function of the time of exposure. The toxicity or risk of exposure is usually measured by some parameters such as occurrence, number, duration, and time pattern of an event. The event may be an absorbing (irreversible) event (e.g., death), a...

Vaccine Clinical Trials

Similar to clinical development of drug products, there are four phases of clinical trials in vaccine development. Phase I trials are referred to early studies with human subjects. The purpose of phase I trials is to explore the safety and immunogenicity of multiple dose levels of the vaccine under investigation. Phase I trials are usually of a small scale. Phase II trials are to assess the safety, immunogenicity, early efficacy of selected doses of the vaccine, and generate hypotheses for...

Parallel Group Designs

A parallel group design is a complete randomized design in which each patient receives one and only one treatment in a random fashion. Basically there are two types of parallel group design for comparative clinical trials, namely, group comparison or parallel-group designs and matched pairs parallel designs. The simplest group comparison parallel group design is the two-group parallel design which compares two treatments e.g., a treatment group vs. a control group . Each treatment group...