Critical efficacy data

It is therefore essential to incorporate procedures that will ensure not only that the clinical data are collected in a uniform and similar manner at each investigating centre but that they are also handled and analysed in an identical manner. Measures such as the use of compatible validated computer systems and similar databases will allow the merging of data. At each centre, critical efficacy data should be determined with identical procedures and, where appropriate, these should be specified in protocols... 

In the majority of clinical trials, external (central) laboratories are contracted to analyze biological samples which are acquired during the clinical trial. Laboratory results are often critical, for example primary efficacy data, and, therefore, warrant systems audits in laboratories. 

Reliable residue data are generated during the development of an a.i. to support the assessment of the consumer risk (residue data and toxicological data) and the impact on the environment (fate and behavior, efficacy and ecotoxicological data). It is critical that these analytical methods are reliably validated. In the guidance document SANCO/3029/99 rev. 4 (11/07/00), harmonized requirements for the residue analytical method are described. Validated analytical methods are required for the following studies ... 

The purpose of this section of an application is to establish that the proposed manufacturing process is suitable and that it will yield consistently product of the desired quality. The concept is closely related to GMP and the detail of conventional manufacturing process validation may not be required. However, data will normally be required for nonstandard manufacturing processes (particularly nonstandard sterilization processes) and for those aspects of manufacture that are critical in terms of product quality, e.g., in the manufacture of modified-release products the quality, safety, or efficacy of which will be affected by the method of manufacture. 

It is not often that researchers find their work leading to such widespread changes of behaviour. Still, the 44 per cent figure reveals a split opinion. Most physicians did not intend to alter their prescribing practices. Our analysis has provoked a vociferous and continuing debate on the effectiveness of antidepressants and the circumstances under which they should be prescribed. In this chapter I consider and respond to the various criticisms that have been levelled at our data-based conclusions about the efficacy of antidepressants. 

Interpreting these results on a detailed molecular basis is difficult because we have at present no direct structural data proving the nature of the split Co(IIl/lI) voltammetry (which seems critical to the electrocatalytic efficacy). Experiments on the dissolved monomeric porphyrin, in CH-C solvent, reveal a strong tendency for association, especially for the tetra(o-aminophenyl)porphyrin. From this observation, we have speculated (3) that the split Co(III/II) wave may represent reactivity of non-associated (dimer ) and associated forms of the cobalt tetra(o-aminophenyl)porphyrins, and that these states play different roles in the dioxygen reduction chemistry. That dimeric cobalt porphyrins in particular can yield more efficient four electron dioxygen reduction pathways is well known (24). Our results suggest that efforts to incorporate more structurally well defined dimeric porphyrins into polymer films may be a worthwhile line of future research. 

The above data suggest an important role of reactive oxygen species in the development of heart diseases. This suggestion has been supported by many studies, which also demonstrated a potential efficacy of antioxidants, free scavengers, and chelators in the treatment of these diseases. Mitochondrial oxygen radical overproduction can probably be one of the critical causes. 

Issue Industry and the regulatory authorities need to agree on (1) what constitutes a valid efficacy claim for each product type, (2) the test methods used to generate data in support of these claims and (3) a test method development strategy and plan for the most critical areas where methods are inadequate or missing. 

We apply our classification of study designs throughout the text to help the clinician interpret the quality of results from clinical trials. Further, we give the critical reader a perspective on the depth and validity of the available data. Most studies in our analyses of drug efficacy are class I or II, and if not, we discuss the studies accordingly. 

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