Full development decision

Sometimes the terms early and late clinical development are used instead of the phases 1, 2 and 3. Early development refers to all studies before the full development decision point, whereas late clinical development refers to all studies thereafter. 

FIGURE I Life cycle for new drug development. EIH, entry into humans FDDP, full development decision point. 

Internal summary reports and formal proposals for management are often assembled in preparation for development milestones (e.g., candidate selection and full development decision). Research reports for critical data are written for products as they progress through development. However, reports for failing studies or discontinued programs are often not prepared and these can be equally useful since history tends to repeat itself. Because of the time and resources required to prepare such reports, a conscious decision should be made if the value added warrants the effort. 

Internal summary reports and formal proposals for management are often assembled in preparation for development milestones (e.g., candidate selection, full development decision). 

One of the measures of the quality of the preregistration clinical programme is the total time from the decision to enter full development to the first regulatory approval in a major market. It is also important to monitor quality in other ways. One option is to assess the frequency with which predetermined milestones are achieved. More subtly, quality can be assessed by examining the number of incomplete, inaccurate or indecipherable CRFs that are returned or the number of protocol amendments made which are not based on new information. Milestones may still be achieved when quality is poor, that is, when there is inefficiency, but this means that they were wrongly established and can be improved if efficiency improves. 

As discussed in the introduction, results of ED are intended to give a clear indication that the drug is a serious candidate for full development to product licence, or that it is not viable and development should be stopped forthwith. Sometimes it takes a little longer before the picture becomes clear but the aim should be to make a go/no-go decision at the earliest opportunity. 

Documentation abstracts, useful as they are, may also prove inadequate for final decisions, which would make it necessary for the searcher to obtain and examine copies of full patent specifications. Although the increasing availabihty of sets of full specifications on CD-ROM at modest cost is making it easier for searchers to have in their collections copies of those specifications they might need to consult, the necessity to go beyond computer output, whether to abstracts or full specifications, is stiU one of the bottlenecks of computer searching, and therefore an area in which significant new developments are hoped for. 

Whilst LCA is a powerful tool, which will become increasingly useful, as it is refined and becomes more objective, its complexity and cost, and the length of time taken to carry out a full analysis make it an impractical tool to use on a day-to-day basis for research and development chemists and chemical engineers. What is really required for most practising technologists is a simple set of metrics to aid the decision-making process involved in choosing one synthetic route or product over another. 

I now shall present a summary of an application of decision analysis to a specific chemical, perchloroethylene (PCE), a widely used dry cleaning solvent (also called tetrachloroethylene). Full details of this application are presented in an EPA report (5). Perchloroethylene was selected for us by the staff of the EPA Office of Toxic Substances as representative of chemicals on which EPA needed to make an unreasonable risk determination under TSCA. Our analysis was carried out as an exercise in methodology development and not to support any specific regulatory activities by EPA concerning perchloroethylene. 

Biological reduction. Biological reduction of chlorate and bromate was still in development at the time of decision-making [2, 3]. It is known that this anaerobic process works well on a bench-scale. Studies on a full-scale basis are presently being conducted. 

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