Clinical studies/trials design

Define the following aspects of clinical trial study design ... 

As defined by ICH and GCP guidelines, a subinveshgator is any individual member of the clinical trial team designated and directly supervised by the PI to perform trial-related procedures or make trial-related decisions (Sechon 1.56, p. 13). ° Examples of subinvestigators include other physicians, pharmacists, pharmacologists, nurses, and study coordinators. 

A good clinical trial is designed to take account of the variability in response (either efficacy or adverse event) that is expected when a new active drug is tested. This response depends on an individual s genetic make-up, and on a number of environmental factors, such as disease state, other drugs and age. The size of the trial and the selection of study subjects are carefully determined to reduce the variability in response to a minimum (i.e. to maximise the sensitivity of the trial) so that the trial endpoints can be determined with as much certainty as possible. 

PTCA). The primary objective was to evaluate the occurrence of major adverse cardiac events (MACE) [death, recurrent myocardial infarction (Ml), or clinically driven target lesion revascularization] 30 days postprocedure. The secondary objectives were to evaluate the binary restenosis, incidence of (sub)acute stent thrombosis at 30 days follow-up, MACE at 6 and 12 months and the QCA endpoints at 6 months. This study was designed to allow a comparison with the patient population and the results of a larger randomized DISTINCT (BiodivYsio stent in controlled clinical trial) study previously conducted in the U.S. 

There are two components to evidence-based medicine and two related sets of responsibilities. The first component is clinical research. Clinical research is a scientific endeavor that provides evidence concerning potential therapeutic interventions. This book has focused on one particular therapeutic intervention, drug therapy. Once clinical trials have been conducted, the evidence obtained is published in clinical communications in journals. Everyone involved in clinical research has the responsibility to provide the best possible evidence in this manner. As noted throughout the book, this includes all aspects of clinical research study design, experimental methodology and clinical operations, analysis and interpretation, and also accurate and complete representation of study findings in clinical communications as discussed in Section 13.6. 

Phase II clinical trial studies are designed primarily to explore the relationship between the dose level and frequency of administration and the efficacy and safety observed in patients with a particular therapeutic indication or disorder. Normally, a primary endpoint is selected to evaluate the efficacy however, secondary endpoints are often included to establish criteria for monitoring patients in the more definitive phase III clinical trials. Phase II clinical trials are commonly... 

The previous sections have described how a clinical trial is designed, the documentation that must be prepared, and the preparation, documentation and dispatch of clinical trial material. None of these areas should be carried out in isolation and need to be addressed long before the first study subject is recruited. The pharmaceutical physician cannot be responsible for all these tasks unless he or she is carrying out independent research. Even then, he or she should seek expert help in the design of the study in relation to the statistical analysis and how the data will be collected and entered onto a database. 

Synthetic surfactant (Exosurf) was studied in a placebo-controlled trial of patients with ARDS. While this therapy also failed to show benefits, the drug was aerosolized over 5 days to administer 240 mL Exosurf. Since aerosolized surfactant is poorly delivered and was shown recently to be ineffective in neonates with RDS, this trial cannot be considered of value in gauging the efficacy of surfactant for ARDS. Also, natural surfactants that also have surfactant proteins may be a better choice. Phase 111 studies using a recombinant SP-C-based surfactant showed reduced mortality for the subgroup of patients with ARDS secondary to direct insults, although no benefit was seen for the total study population. It is important to consider etiologies for ARDS when future clinical trials are designed. 

Future Clinical Trials. Study C-04-59 is designed to evaluate the dose and administration frequency of anecortave acetate depot every three months (15 mg) or six months (15 or 30 mg). Inclusion criteria are similar to those of the previous trials. 

Phase II clinical trials are designed to evaluate the producfs efficacy and side-effect profile. About 100-300 patients are involved. Data obtained are used to characterize the dose-response relationship. The costs involved are about 10-100 million Euro over 1- to 2-year period. The success rate is about 40%. Studies performed may be characterized by a single or multicenter study, single- or double-blinded with a control group and randomization of the patients. Amongst the most common reasons for failure at this phase are poorly designed studies and ineffective or unsafe products. 

---