Monitoring of Trials

Heading 3 deals with CEIC. Art. 41.2 emphasizes that the hospital pharmacist should be a member of the CEIC, and Art. 42 describes the duties and functions of the CEIC ...to evaluate the protocol and the research team, evaluate the written information to be given to the subjects of the research, perform monitoring of trials. ... 

Figure 15.33 Equipment for rubblisation. (a) Multiple head breaker and (b) grid roller. (From Coley, C. and Carswell, I., Improved Design of Overlay Treatments to Concrete Pavements. Final Report on the Monitoring of Trials and Schemes. TRL Report TRL 657. Crowthorne, UK Transport Research Laboratory, 2006.)...

A regularly formed crystal of reasonable size (typically >500 pm in each dimension) is required for X-ray diffraction. Samples of pure protein are screened against a matrix of buffers, additives, or precipitants for conditions under which they form crystals. This can require many thousands of trials and has benefited from increased automation over the past five years. Most large crystallographic laboratories now have robotics systems, and the most sophisticated also automate the visualization of the crystallization experiments, to monitor the appearance of crystalline material. Such developments [e.g., Ref. 1] are adding computer visualization and pattern recognition to the informatics requirements. 

The widespread acceptance and use of the Internet as a means for communication in clinical trials has revolutionized the way clinical trials information is disseminated among the various individuals and collaborating organizations running and monitoring these trials. A trial s web site provides trial... 

The evaluation of all NADA analytical methods was previously conducted exclusively by the CVM. Since 1995, the CVM has offered sponsors of NADA residue methods the option of conducting the method trial through a Sponsor Monitored Method Trial (SMMT) process. The SMMT is conducted according to CVM specifications with CVM oversight. The resultant performance data must be reviewed and judged acceptable by CVM before the method is approved. 

A comparison has been made between small scale test results and a field trial at a 17-ton scale for a solid compound [217]. The test results from a very sensitive calorimeter (Thermal Activity Monitor from ThermoMetric, Sweden) were substituted in a model, and the self-heating situation in bulk containers was predicted. The large-scale trial was carried out in a steel rectangular container lined with polyethylene. A control device was used to keep the container at a temperature of 40 to 45°C. Several thermocouples enabled monitoring of the temperature as a function of time in different places in the large container. 

This is the organization that is contracted by the Sponsor to conduct and monitor the trial. It also provides a certain measure of independence to the trial and enhances the validity of the trial results to be unencumbered by conflict of interest. 

But even a small-scale trial-and-error strategy has to be organised within society. As discussed in the previous section, iimovations are rather improbable and disadvantaged by stractural frameworks. Iimovations depend upon freedom for them to be developed. At the same time safety barriers have to be formulated within which the search process can move freely. For example, possible environmental effects must be anticipated, necessitating controlled release in small increments and retrievability must be ensured. (Quantitative and qualitative restrictions must be imposed so that retrieval and repair options can still be effective if a trial is aborted. This approach is more successful if the persistence and spatial range of a chemical is low than for persistent chemicals like CFCs and PCBs. This requires that limited Teaming spaces or experimentation spaces have to be created intentionally under technical and economic risk considerations. Small increments and a steady increase are to be preferred, accompanied by intensive monitoring of detectable consequences. 

The monitoring of volunteers/patients decreases through the programme. A volunteer will stay in a clinic and will be very closely monitored for any signs of toxicity, whereas a patient in a Phase III trial may only be required to return to their physician periodically. 

The conduct of explanatory trials will include close monitoring of the study in an attempt to ensure strict adherence to the protocol. There is likely to be exhaustive recording of data. In contrast, the conduct of pragmatic trials will tend to mirror real life. There will be attempts to minimise data recording, but there is hkely to be exhaustive follow-up of all patients. 

It is also necessary to make provision for the monitoring of adverse reactions occurring in clinical trials using Community surveillance (pharmacovigilance) procedures in order to ensure the immediate cessation of any clinical trial in which there is an unacceptable level of risk. 

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