Exploratory phase

Neijt IP, Engelholm SA, Tuxen MK, et al. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carbo-platin in advanced ovarian cancer. J Clin Oncol 2000 18 3084-3092. 

Screening designs are mainly used in the intial exploratory phase to identify the most important variables governing the system performance. Once all the important parameters have been identified and it is anticipated that the linear model in Eqn (2) is inadequate to model the experimental data, then second-order polynomials are commonly used to extend the linear model. These models take the form of Eqn (3), where (3j are the coefficients for the squared terms in the model and 3-way and higher-order interactions are excluded. 

Therapeutic exploratory (Phase lb/II) Explore use for the targeted indication Estimate dosage for subsequent studies Provide basis for confirmatory study design, endpoints, methodologies Earliest trials of relatively short duration in well-defined narrow patient populations, using surrogate or pharmacological endpoints or clinical measures Dose-response exploration studies... 

These four ingredients are utilized in a process falling into two broad phases an exploratory phase and a confirmatory phase. The exploratory phase isolates patterns in and features of, the data and reveals them, allowing an inspection of the data before any firm choice of actual hypothesis testing or modeling methods has been made. 

There may, of course, be cases, especially in the early exploratory phase, where the sample size has been chosen on purely practical or feasibility grounds. This is perfectly acceptable in that context and the sample size section in the protocol should clearly state that this is the case. 

One question that often arises is which test should I use as I don t know what kind of effect I am going to see My short answer to this question is that in a confirmatory setting you should know By the time you reach that stage in the drug development programme your knowledge of the disease area and the treatment, in combination with the endpoint, should enable accurate prediction of what should happen. Of course, earlier on in the programme you may not know and in this exploratory phase it is perfectly valid to undertake both tests to explore the nature of the effects. 

This paper describes the preliminary and exploratory phase of an investigation of Chinese ink in Far Eastern paintings—its properties and its variability. To clarify what such investigation might achieve, we must first look briefly at the history and method of manufacture of the ink. Note that Chinese ink has been variously called China ink, India (or Indian) ink, Japanese ink, and occasionally by its Japanese name, sumi. The Chinese word, less used, is mo. 

II EARLY INVESTIGATIONS / EXPLORATORY PHASE THE SEARCH FOR CATALYTIC SYSTEMS. 

Random screening is usually too time consuming but a certain randomness is desirable during the exploratory phase because unexpected effects are bound to occur. Again a citation Tai [1] says regarding the discovery of the Ni/tartrate/NaBr catalyst and its application to p-keto ester hydrogenation "It was sheer luck that methyl acetoacetate was employed as a substrate...". 

If the study is exploratory, it is not uncommon to have a multitude of creative ideas about the nature of the biomarker response and its relationship to the exposure. Ideally, some comparisons of particular interest are specified in advance. The analyses can then be divided into confirmatory and exploratory phases. Two key considerations in such exploratory studies are selection bias and confounding both were discussed in the section on the sam-... 

The objective of the present work was to develop a deacidification process which could be applied simultaneously to a substantial number of books and be much more reasonable in time and cost than the singlepage procedures. The exploratory phase of the project was started in 1970 the past six years work have culminated in a process which inexpensively deacidifies about 85 lb of books in 60 min and which substantially retards their subsequent deterioration rate. 

In the exploratory phases of product and process research and development, generally little or limited data are available for model parameterization. However, chemists and engineers need to evaluate a multitude of possible molecular or process variations. Rather than high accuracy, successful evaluation depends on the ability to discard the least viable options and select better options for further detailed studies. Estimation methods that give reliable results for new or unknown species are required. The well-known group-contribution methods, like UNIFAC, have demonstrated their value in cases where the molecules can be decomposed to functional groups for which parameters are already available. 

In recent literature, the concept of surrogate endpoint has become inextricably linked to the term proof of principle or proof of concept study. There is nothing fundamentally new in this idea. It is an attempt by sponsors to design, execute and interpret small scale , preferably shortterm trials at the exploratory phase of development in which a selected surrogate (or surrogates) is determined as the go/no go decision point for... 

E. 1. Ette, V. Garg, and A. Jayaraj, A rational approach to drug development the exploratory phase. Clin Res Regul Affairs 21 155-177 (2004). 

In addition, the effect of drug administration on the biomarker concentration should be factored in for the standard curve dynamic range. This is often a challenge during the exploratory phase with a novel biomarker because the modulation by a drug candidate may not be known and postdose incurred samples would not be available for the initial tests. 

Process development follows an overall development plan that coordinates all the various disciplines involved. It is typically performed in three cycles to allocate resources and thus manage product pipelines efficiently, and involves a scale-up of up to 1000-fold and more [128]. During the exploratory phase, a research method is used to generate small amounts of the respective MAbs to investigate target-specific effects in-vitro. Important technical goals at this stage are feasibility and speed. 

Drug interaction studies should be planned in the early exploratory phase of drug development. The in vivo studies should be conducted according to the... 

In addition to ester-based polyesters, a great deal of research activity has been directed to other types of absorbable polymers, but the clinical relevance of their properties practically halted their evolution beyond the exploratory phase. Typical examples of these polymers have been covered in a review by Shalaby and include those based on polyanhydrides, polyortiioesters, poly-phosphazenes, and certain polyamidoesters. ... 

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