Clinical trials protocol implementation

Clinical Trials Data Bank We have established a clinical trials data bank to collect information on your clinical trials protocols. Please list your protocols for serious and life-threatening conditions [Food and Drug Administration Modernization Act of 1997 section 113]. When finalized, you should list your protocols in accordance with our Draft Guidance for Industry—Information Program on Clinical Trials for Serious or Life-Threatening Diseases Implementation Plan, June 2001. 

Regulatory authorities play an important and active role to ensure regulatory compliance in the conduct of a clinical trial. Agencies such as the FDA inspect clinical studies. An inspection of a trial may reveal that the protocol is not being followed strictly, the Investigator may not be involved with the project as much as is expected, there may be a lack of patient care, changes to the protocol may not have been relayed to the IRB, and so on. In such cases, corrective actions have to be implemented immediately and the FDA must be satished before the trial can continue. Deficiencies found are reported on Form 583. 

The IRB is responsible for judging all studies to be conducted at the centre concerned by reviewing protocols, the informed consent sheet, the investigator s brochure and other materials relating to the conduct of clinical trials. The IRB is also responsible for monitoring whether the clinical trials are conducted in compliance with both GCP and IRB s requirements, if any. When the study period of a clinical trial exceeds 1 year the IRB should review the study every year. As the new GCP allows the study sponsor to pay a reasonable amount of money to the study subjects, the IRB is expected to review whether the amount and method of payment is reasonable and does not infringe upon the ethical aspects of the study. Also, the advertisement of a trial for patient recruitment is allowed, but the IRB s approval to implement this at the study centre is required. 

The Trial Simulator (Pharsight Corp., http //www.pharsight.com) is a comprehensive and powerful tool for the simulation of clinical trials. Population PK/PD models developed with tools mentioned in Section 17.10.3 can be implemented in a Trial Simulator. In addition, treatment protocols, inclusion criteria, and observations can be specified. Also covariate distribution models, compliance models, and drop-out models can be specified. All of these models can be implemented via a graphical user interface. For the analysis of simulation results a special version of S-Plus is implemented and results can also be exported in different formats, like SAS. 

The research program at NIH also uses pharmacists in many of its 14 institutes. Pharmacists in the National Cancer Institute s (NCI s) Pharmaceutical Management Branch are involved in anticancer drug development, protocol development, collection of clinical data, distribution of NCI investigational drugs and the Treatment Referral Center. In addition, the intramural program of the NCI has a pharmacokinetics laboratory where pharmacists perform basic and clinical research. The National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS pharmacists participate in protocol development and implementation, and act as consultants to more than 300 pharmacists involved in NIAID-sponsored AIDS clinical trials. 

The principles of the Directive should remove the complexity of clinical trial application, authorization and regulation in existing, new, and future Member States. Thus, substantial amendments to protocol that impact on safety of the subjects or where there is a change in the interpretation of data on the IMP must be notified under the legislation underpinning the Directive. This common process will obviate current disparate national procedures that range from a simple notification scheme to a complex authorization proce-dure. Implementation of the Directive cannot be expected to alter national requirements for provision to examiners of Information to Subjects and Informed Consent forms in local languages. 

Thus, they established procedures for clinical trials and other experimentation with humans in which researchers are expected to follow a precautionary protocol for selecting patients and applying experimental methods and products to them, monitoring their response, and then do full and timely reporting of any adverse outcomes to enable open discussion and evaluation of the causes, quick determination of corrective actions needed for patient safety, and rapid dissemination and implementation of the corrective actions in all related research projects. It now appears that this model for safeguarding human subjects needs reinforcement for it to be sufficient in the competitive and economically opportunistic culture in which gene therapies are tested. 

However, differences between the care provided to patients in the trial and that provided to patients in this group may be due as much to secular trends in the provision of medical care as they are to the adoption of a study protocol. For example, length of stay in the United States has decreased since the early 1980s, due in part to the implementation of the Medicare Prospective Payment System. Thus, historical cohorts from earlier periods may have had longer lengths of stay as inpatients than is currently seen in clinical practice. These data may suggest a protocol-induced decrease in length of stay when one actually does not exist. 

Ely EW, Baker AM, Dunagan DP, et al. Effect of the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996 335 1864-1869. Kollef MH, Shapiro SD, Silver P, et al. A randomized controlled trial of protocol-directed versus physician directed weaning from mechanical ventilation. Crit Care Med 1997 25 567-574. Saura P, Blanch L, Mestre L, et al. Clinical consequences of the implementation of a weaning protocol. Intensive Care Med 1996 22 1052-1056. 

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