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chosen should balance realism and rigor. This is easier to say than to do, and some specific comments are appropriate. The data available at early checkpoints will be limited. Dosing will be of short duration. Patient numbers enrolled in studies will be small. Dose regimens will not be optimized, and hence, neither will the efficacy delivered. It is possible that dynamic markers will have been studied rather than the intended clinical endpoints. It is important not to fall into the trap of mindlessly extrapolating required labeling to early checkpoints. This applies particularly to ultimately desired statistical statements for which early trials will not have been powered. |
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The primary purpose of setting Go/No Go criteria is to provide an answer to the question, Do the data available at this time justify further investment in the project? |
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For some projects, competitive products may have helped define the hurdle height of the checkpoint. For some pioneer products, demonstration of dose-related activity against selected markers in early studies may be as much as can reasonably be achieved to encourage investment in the next stage of development. |
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When should the key checkpoint for full development to the market be set? It may be that efficacy is revealed only at the completion of phase 3 scale trials. This could be the case in prophylaxis studies where many patients are enrolled of whom only a small percentage develop a disease condition and contribute the vital efficacy data. In some indications, clinical efficacy can be clearly demonstrated in modestly sized phase 2 trials. When Go/No Go project checkpoints occur and how their criteria are quantified are very much specific to a project. The outcome of Go/No Go checkpoints is not necessarily go or stop. Phase 2 data may reveal that the dose response has not been adequately explored, and phase 1 studies may reveal poor pharmacodynamic results and also suboptimal bioavailability for the formulation studied. In each case, plans can be redesigned to achieve a successful outcome albeit with delay to the project. |
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5.
Back-Up and Follow-Up Strategy |
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Discovery and development strategy must be closely integrated to ensure success in bringing products to market. Back-up compounds offer no commercial differentiation from the lead compound in development, whereas a follow-up compound does. The high failure rate in development demands a well-planned, back-up strategy. Sometimes this strategy is simply to identify a back-up candidate and await the phone call from development notifying failure of the lead candidate. Some companies adopt more aggressive |
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