Exploratory trials

Johnson, E. J., K. A. McDonald et al. (2008b). Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutr. Neurosci. 11(2) 75-83. 

ICH E9 makes a very clear distinction between confirmatory and exploratory trials. From a statistical perspective this is an important distinction as certain aspects of the design and analysis of data depend upon this confirmatory/exploratory distinction. 

Therapeutic exploratory trials are conducted if the results of the human pharmacology trials are considered positive (someone has to decide that the results are positive). These trials involve the comprehensive assessment of the investigational drug s safety in perhaps 200-300 individuals with the disease or condition of interest. They are typically conducted by clinical pharmacologists, and participants in these trials are often hospitalized and can therefore be closely monitored. Extensive data are collected, including self-report assessments by the participants and biochemical assessments. 

If the therapeutic exploratory trials are successful (someone has to decide if this is the case), the... 

Tight experimental control is an extremely important goal in all experimental trials. Consequently, we talk a lot about how to maximize such control in these trials. However, it is simply a realistic consequence of the way that therapeutic confirmatory trials have to be conducted that the experimental control cannot be quite as tight in these trials as it is in human pharmacology trials and therapeutic exploratory trials. 

The advantage of very tight control in early Phase II (therapeutic exploratory) trials is that the "pure" efficacy of the drug can be assessed as well as possible. The drug has every chance to demonstrate its efficacy in these circumstances. 

A total of 290 participants were studied in the first therapeutic exploratory trial of on investigational antihypertensive drug. Of the 150 individuals treated with the test treatment, 32 reported fatigue. Of the 140 treated with placebo, 19 reported fatigue ... 

It is also appropriate to note that not all clinical trials utilize formal sample size estimation methods. In many instances (for example, FTIH studies) the sample size is determined on the basis of logistical constraints and the size of the study thought to be necessary to gather sufficient evidence (for example, pharmacokinetic profiles) to rule out unwanted effects. However, when the objective of the clinical trial (for example, a superiority trial) is to claim that a true treatment effect exists while at the same time limiting the probability of committing type I or II errors (a and P), there are computational methods used to estimate the required sample size. The use of formal sample size estimation is required in therapeutic confirmatory trials, this book s major focus, and strongly suggested in therapeutic exploratory trials. 

Rogers C G, Tyson J E, Kennedy K A, et al. (1998). Conventional consent with opting in versus simplified consent with opting out an exploratory trial for studies that do not increase patient risk. J Paediatr 132 606-611. 

Yancheva S, Ihl R, Nikolova G, Panayotov P, Schlaefke S, Hoerr R (2009) Ginkgo biloba extract EGb 761(R), donepezil or both combined in the treatment of Alzheimer s disease with neuropsychiatric features a randomised, double-blind, exploratory trial. Aging Ment Health 13(2) 183-190. doi 10.1080/13607860902749057... 

Garamelli P, Laks ], Palmini AL, Nitrini R, Chaves ML, Forlenza OV, et al. Effects of galantamine and galantamine combined with nimodip-ine on cognitive speed and quality of life in mixed dementia a 24-week, randomized, placebo-controUed exploratory trial (the REMIX study). Arq Neuropsiquiatr 2014 72(6) 411-7. 

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