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course revealed that virtually all protocols have at least one amendment during the study. The reasons appear to cover the full range, from reliance on well-established designs without allowing newer, more creative ideas to be considered and, at the other extreme, not testing new methods for the current application. For example, in a recent angina study, treadmill exercise testing was used as the primary efficacy criterion. This is, of course, extremely well-validated methodology, but, in this case, the patients were elderly, so the exercise protocol was substantially modified to reduce the physical demand. The problem was that with such a mild exercise protocol, less than half the patients recruited showed sufficient electrocardiogram (ECG) changes to qualify for randomization. A quick pilot study would have alerted the sponsors before committing to major cost. |
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B.
The Role of Senior Management |
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A recurring theme in clinical research is the role of senior management. By this we mean not the head of clinical research, not the head of R & D, but corporate management. The costs and risks of failure in the clinical phases are so large that they should be occupying much of top management's attention. Yet, in many companies, requirements, objectives, budgets, and deadlines, are imposed without any negotiation. On top of this, major changes are commonly dictated by management, usually by changing priorities. How can the clinical project manager fulfill top management's aspirations, within an increasingly constrained environment? |
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C.
Predicting the UnpredictableManaging Risk |
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All research and development must involve some risk. Figure 3 shows some of the risks typically encountered in the main stages of a typical clinical trial. The values for risk level and lateness are those usually applied in the author's company when planning studies. They may differ from those of the reader but are useful rules of thumb. Whatever rules are used, they will almost certainly be better than no risk assessment at all. |
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1.
Risk Distribution in Clinical Phases |
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Delivering the results on time, to the required standard, may have a lower risk in phase I than in later phases, mainly because subjects are healthy and not potentially complicated patients, and thus, recruitment can be predicted with some confidence. However, first administration to humans is something of a leap into the unknown, and safety problems are always to |
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