Compliance in clinical trials

MacKintosh, D.R. Zepp, V.J. Source documentation a key to GCP compliance in clinical trials. Appl. Clin. Trials Mar. 1996, 42 6. 

B. Spilker, Methods of assessing and improving patient compliance in clinical trials, in Patient Compliance in Medical Practice and Clinical Trials, J. A. Cramer and B. Spilker B (Eds.). Raven Press, New York, 1991, pp. 37-56. 

Wood D. The Management of 21 CFR 11 Compliance in Clinical Trials Mon itor. Summer 2003 39-43. 

Detailed guidelines on the quaUfications of inspectors who should verify compliance in clinical trials with the provisions of good manufacturing practice for an investigational medicinal product to implement the directive on Clinical Trials on medicinal products for human use. June 2002... 

Mawhinney H, Spector SL, Kinsman RA, Siegel SC, Rachelefsky GS, Katz RM, Rohr AS. Compliance in clinical trials of two nonbronchodilator, antiasthma medications. Ann Allergy 1991 66 294—298. 

Computerized Systems Used in Clinical Trials, found at http //www.fda.gov/ora/compliance ref/bimo/ffinalcct.pdf. 

Increased incidents in clinical trials have lead to a recognition of the weaknesses of informed consent procedures. Actually, the FDA has reported that such deficiencies are the poorest area of GCP compliance for more than 12 years (FDA Reports, 2000, Office of Inspector General, 2000a, b). 

Administration of the Drug. As it is with accurate identification of a drug, so it is that its administration must at times be held in question. Subject compliance with the study protocol is not a rare problem in clinical trials. Complete noncompliance sometimes occurs. 

Poor adherence to the schedule of taking the study medication will obviously confound interpretation of the efficacy and safety of the drug. There is usually good compliance in clinical pharmacology studies, especially those conducted in units where drugs are administered by the staff. However, in clinical research trials adherence to medication may be poorer. 

Food and Drug Administration (FDA). Guidance for Industry - Computerised Systems Used in Clinical Trials. RockviUe, MD Division of Compliance Policy, 1999. 

The verification of compliance with the standards of good clinical practice and the need to subject data, information and documents to inspection in order to confirm that they have been properly generated, recorded and reported are essential in order to justify the involvement of human subjects in clinical trials. 

All pivotal studies, such as the main teratology study and any range-finding study performed to support the inclusion of women of childbearing potential in clinical trials, must be performed in compliance with Good Laboratory Practice. 

Failure to comply with cGMP requirements is just one of the areas during clinical trials that may result in compliance issues. Improperly assigned expiration dates, inadequate procedures related to the extension of expiration dates, and abreakdown in any of the steps from manufacture of a clinical trial material to its use in a clinical trial could result in compliance issues. Starting with the manufacture of clinical trial material, there must be well-designed and documented procedures that effectively involve all appropriate persons and departments to assure that only material within specifications is used in clinical trials. There must be procedures that ensure the timely availability of clinical supplies, timely and appropriate extension of expiration dates, timely investigation of out-of-specification (OOS) results and rapid notification of appropriate persons, timely recall of all OOS and expired materials, and timely resupply with fresh materials. Depending on the severity of the compliance issue, the clinical trial could be considered compromised. 

The first concept made explicit in this document is that the FDA has jurisdiction over materials that are used in clinical trials prior to approval and market launch thus some 12 years prior to the start of PAIs by the FDA it had established an industry standard that compliance to cGMPs, was required during the manufacture of clinical trial materials. 

Information for Clinical Investigators. This Web page includes guidances, information on Institutional Review Boards, and protection of human subjects in clinical trials, along with links to clinical regulatory and compliance resources. 

FDA issues CPG Enforcement Policy for 21 CFR Part 11 FDA publishes Computerized Systems Used in Clinical Trials FDA issues CPG Year 2000 Computer Compliance... 

One factor to keep in mind when evaluating disulfiram is that its effects may be enhanced considerably if its u.se is combined with a behavioral program that in part consists of supervised administration of the disulfiram (e.g., by the patient s spouse) to the patient (Hughes Cook, 1997). This apparently addresses a major practical problem with using disulfiram clinically It typically requires daily administration of the prescribed dose, and patients tend to show poor compliance with such a regimen. Disulfiram implants have been tried as another w ay to solve the compliance problem, but their effectiveness has not been shown clearly, and the bioavailability of the implanted disulfiram has not been demonstrated in clinical trials. Additional well-controlled studies of supervised disulfiram therapy would allow us to specife the conditions under which its administration is most likely to enhance outcomes. 

A multitude of external providers are used to deliver services in clinical trials, for example CROs, site management organizations (SMOs) and academic research organizations (AROs). To ensure that they are capable of providing the services in a reliable manner and to the standards expected in compliance with current regulatory requirements, capability audits are conducted at service providers prior to contracting. 

Averbuch M, Weintraub M, Pollack DJ. 1990. Compliance assessment in clinical trials the MEMS device . J. Clin. Res. Pharmacoepidemiol. 4 199-204. 

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