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In recent years, major progress has been made in the development, investigation and clinical application of novel immunosuppressive drug therapies to prevent acute rejection. Critical to the ultimate clinical application of new drug therapies is the ongoing performance of large multi-center clinical trials. However, there has been a paucity of infectious disease monitoring built into these protocols. Given that infectious complications are a major source of morbidity and mortality in transplant recipients, the assessment of the magnitude of risk of infection associated with a given immunosuppressive strategy may be as important as the assessment of rejection. For the above reasons, screening, monitoring and reporting recommendations for common transplant-associated infections were developed for use in clinical trials evaluating immunosuppressive strategies. These recommendations have two major goals: (i) to provide clinically relevant definitions for tracking infectious complications occurring in participants in immunosuppressive trials and (ii) where appropriate, to recommend specific laboratory monitoring and surveillance methods.
In recent years, major progress has been made in the development, investigation and clinical application of novel immunosuppressive drug therapies to prevent acute rejection. Critical to the ultimate clinical application of new drug therapies is the ongoing performance of large multi-center clinical trials. However, there has been a paucity of infectious disease monitoring built into these protocols. Many protocols allow for passive surveillance and reporting of infections as adverse events. Even when protocols stipulate monitoring for a particular type of infection, different sites within a single multi-center study may have varying definitions for infection and use diverse testing assays. Accordingly, accurate assessment of the risk of infectious disease complications associated with a new immunosuppressive regimen is often impossible. Given that infectious complications are a major source of morbidity and mortality in transplant recipients, the assessment of the magnitude of risk of infection associated with a given immunosuppressive strategy may be as important as the assessment of rejection.
Purpose of Recommendations. For the above reasons, screening, monitoring and reporting recommendations for common transplant-associated infections were developed for use in clinical trials evaluating immunosuppressive strategies. These recommendations have two major goals: (i) to provide clinically relevant definitions for tracking infectious complications occurring in participants in immunosuppressive trials and (ii) where appropriate, to recommend specific laboratory monitoring and surveillance methods. It is hoped that the adoption of a common set of definitions and laboratory monitoring strategies will allow for accurate assessment of infectious risks associated with novel immunosuppressive strategies. It should be emphasized that when laboratory monitoring is recommended for a specific pathogen, its purpose is to allow accurate comparison of infectious risk in patients receiving differing immunosuppressive regimens as part of a clinical trial. Its purpose is not for management or prevention of specific pathogens and it does not supplant clinical monitoring strategies that may already be in place at participating centers. In fact it is anticipated that for large multi-center trials, the recommended laboratory protocols may not be done in 'real time' but rather through batching of specimens to facilitate monitoring.
Some trials may be sufficiently large to detect statistically significant differences in infectious risk. However, others may be underpowered to detect such differences, depending on the number of patients enrolled and the incidence of a particular infectious complication. Caution should be exercised in the interpretation of nonsignificant trends, especially in smaller trials. At best, such trends may serve as a potential warning, thereby warranting further evaluation and study.
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