Monitoring visits

The requirements of GCP, as described in the ICH guidelines, are presented in Chapter 7 and will not be discussed further here. However, it is emphasised that the standards required of large clinical trials in patients apply equally to small clinical pharmacological studies in healthy subjects. Studies should be conducted in accordance with SOPs. Many SOPs will resemble those pertaining to later phase clinical trials, but some will be specific to healthy volunteer studies. Details of procedures not covered by SOPs should be specified in the protocol. Studies must be monitored by the sponsor or a representative the monitor should not be one of the investigators so that monitoring visits and assessments can maintain objectivity. 

Like BN, WL monitors visits to macrostates. But, while BN updates the weights of all macrostates after many MC steps, WL updates its density of states for the current macrostate after every step. The update prescription is... 

Clinical drug packaging and labeling Drug and supply distribution to sites Clinical monitoring Site initiation visits Interim site monitoring visits Site closeout visits... 

Whether or not during subsequent monitoring visits there are indications of a software error or any issue that would imply noncompliance if so inquire what steps have been documented to correct the problem. 

In conducting studies to determine temporal decay rates, sampled areas should be identified so that the same areas are not re-sampled pre-application and post-application. Likewise, if deposition coupons (e.g. a-cellulose filter paper or cotton gauze patches backed with aluminum foil) are placed on the floor during application of the pesticide formulation to estimate initial deposition rates, care should be exercised to avoid sampling in the areas covered by the coupons during subsequent monitoring visits. 

Following a monitoring visit, the monitor will prepare a monitoring report for sponsor records and follow up correspondence to the trial site. 

In general, study sites should be visited by a monitor at least every four to six weeks. The frequency of monitoring visits will be defined for each individual study and will depend on details such as the study phase, treatment interval and overall duration, enrolment rate, complexity of the study methodology, occurrence of adverse events (AEs) or other significant events, and the nature of the... 

Other possible downsides are the relative paucity of central laboratory facilities especially for assays, and that are accredited to International Standards and also both GLP and GCP compliant. Transport of clinical trial supplies, access of sites to monitoring visits may require days of rail transport rather than air with complications of humidity and temperature extremes on supplies and biological samples. Finally, sectarian violence can break out at any time causing disruption to monitoring of studies and possible danger to foreign monitors. 

The frequency of monitoring visits should be agreed to between the CRO and the sponsor. However, a pre- and post-study visit as well as a... 

Separate SOPs (with checklists for the monitor) for the initiation visit, routine monitoring visits and a closing visit are recommended. 

Before a clinical trial starts, the use of technical aids such as IVRT, remote data entry, and electronic diaries has to be considered. In the section on Monitoring Visits, mention will be made of the use of electronic tracking system that provide status and monitoring reports. All these systems utilise computer systems that must be validated. Double and McKendry described computer validation as the process that documents that a computer system reproducibly performs the functions it was designed to do. The document Guidance for Industry - Computerised Systems used in Clinical Trials published by the FDA in 1999 gives clear recommendations of what is required (also see Section 6.6.4.1). 

The investigator is responsible for the accuracy and completeness of then trial records and any discrepancies found in these records during an audit (ICH 4.9.1). The monitor will review the source documents for accuracy and completeness against the CRFs at each monitoring visit and will provide feedback on their acceptability to the investigators and their staff. Once the initiation visit has occurred, the study site is considered officially started and subject recruitment can begin. 

When a health care authority inspects the site s product accountability records, every detail will be examined, i.e., dispensing, unused, and final disposition of product. Auditors will examine the product accountability procedure and evaluate its acceptability. At the end of the trial, the monitor will ensure the accountability of all investigational product. Any discrepancies will be investigated and documented accordingly in the source document data, the product accountability records, and/or in the monitoring visit report. 

Allow monitoring visits by the sponsor/CRO at a predetermined frequency. During these monitoring visits, the monitor must be allowed to communicate with all site personnel involved in the conduct of the clinical study Report all AEs and SAEs to the sponsor/CRO and follow the special reporting requirements for SAEs... 

Regulations currently stipulate that an active clinical study should be monitored at a minimum of once each year, but in practical terms the rate of subject enrollment and the volume of data collected usually dictate a much higher frequency of monitoring visits. Each interim or periodic monitoring... 

They can be established for the qualifications of CRO personnel (e.g. a senior CRA must have at least 2 years of clinical research experience) timing and content of reports (e.g. the CRA s monitoring report must follow the format of the example given, and a copy of the report must be received by the sponsor within 2 weeks of the monitoring visit) patient enrollment (e.g. each site must enroll a minimum of 10 patients/month for the first 4 months of the study) cycle times (e.g. questions on case report form content, queries , must be generated within 1 week of receipt of the data by the CRO) database accuracy (e.g. the error rate as determined by comparing actual case report forms with the CRO database must be no more than... 

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