Informed consent, clinical trials process

Informed consent—Permission to proceed with a medical procedure, test, or experiment, based on full understanding of the process, its risks, and benefits. There are strict rules requiring informed consent to protect the subjects of experiments, including clinical trials. 

This inspection process has recently been augmented with the establishment of an Office of the Inspector General (OIG) which reports at the level of the Secretary, not the FDA Commissioner. One of the first announced targets of the OIG, selected from the entire realm of foods and dmgs that FDA regulates, is clinical trials. In particular, the OIG is actively investigating informed consent documents, and also has notified institutional review boards (the US equivalent of the ethics committee) that they are in for close scmtiny. 

For this reason, it is remarkable that, in many cases, clinical pharmacists lead the follow-up process for the clinical trials. It was in a pharmacy-promoted audit that a serious deviation in GCP recommendations was detected. In this study, it was concluded that compliance was adequate in 50% of protocols, so-so in 25% of cases, and poor in the remaining 25%. Surprisingly, in 13% of the patients, the informed consent document was not signed in 15% of the cases, the patient s clinical records did not reflect that the patients were included in a clinical trial. 

All consent documents and the entire informed consent process should be designed and implemented to be in compliance with the above-stated regulations, as well as consistent with the principles of the Declaration of Helsinki, World Medical Assembly, Revised 1996, 48th General Assembly, the accepted basis for clinical trial ethics incorporated into the ICH GCP Guideline. 

Source documents are composed of hospital records, office charts, laboratory data sheets, subject diaries, pharmacy dispensing records, recorded data from automated instruments, x-rays, etc. Source documents should be legible and should document that the subject is participating in a clinical trial. Some of the key areas to cross reference source documents to case report forms and regulatory criteria are the informed consent process, inclusion/exclusion criteria, adverse experiences, investigational product administration, concomitant medications administered to the subject during the trial, withdrawal from the study for any reason, and subjects lost to follow-up. 

There are several other key components to trial execution that will require special attention subject recruitment, the informed consent, IRBs/IEC review product accountability, adverse experience and adverse reaction reporting, financial disclosure, and record retention. Each is critical in the overall success of a clinical trial. If one of these is not handled or processed appropriately, the clinical trial will not be used in support of a new product application. Many of these components have been discussed previously in the context of monitoring. Adverse experience and adverse reaction reporting, informed consent, and IRB/IEC are detailed in Chaps. 11 and 20. The remaining key components relative to managing clinical trials will now be addressed. 

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. 

Clinical trial A formal study of a treatment conducted in patients with a specific disease indication. Such studies usually involve comparison with placebo or an alternative treatment and a randomisation process is used to determine the allocation of treatments. Ideally, they also involve blinding of patients and clinicians (i.e. they are double-blind ) to treatment allocations. Conducting a clinical trial involves intervening in patients treatments for research purposes and therefore informed consent from each patient and ethical committee approval are essential (see p. 31). 

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