Clinical trials shortcomings

There seems to be considerable reluctance in some parts of the medical community to acknowledge the benefits of exercise in the treatment of depression. One meta-analysis of clinical trials showed that physical exercise was as effective as psychotherapy or antidepressant medication and much better than no treatment. But the authors concluded that the effectiveness of exercise in reducing symptoms of depression cannot be determined ,45 and the editors of the journal introduced the article with an editorial comment entitled effectiveness of exercise in managing depression is not shown by meta-analysis .46 Why not Because there were flaws in the way many of the studies had been designed. To be fair, there were indeed shortcomings in the studies, but these shortcomings also characterize clinical trials of antidepressants.47 If clinical trials like these do not establish the effectiveness of physical exercise as a treatment for depression, neither do they establish the effectiveness of antidepressants. 

Daptomycin failed to show non-inferiority to controls in a clinical trial for community acquired pneumonia (CAP).74 The clinical failure was explained by subsequent experiments demonstrating that daptomycin is sequestered in lung surfactant.64 This shortcoming of daptomycin is limited to pulmonary pneumonia involving alveoli and does not extend to haematogenous pneumonia caused by S. aureus ... 

There are no Class I clinical trials by Goodhn criteria (Good-lin et al., 2002) comparing the approved therapies for RR-MS. The dials discussed in the following section are all post-marking trials of relatively short duration. Even so, valuable information can be found if their shortcomings are remembered. 

Does the discussion place the results of this study into the perspective of previous clinical trials comparing and contrasting results Does the discussion honestly outline the clinical trial s shortcomings ... 

In vitro biochemical studies of drug metabolism, particularly studies associated with pharmacokinetic (PK) properties and potential toxicological consequences, are essential in drug discovery and development. For over a decade, the major pharmaceutical companies have been promoting such efforts for incorporation into early stages in discovery (Obach, 2001 Smith and van de Waterbeemd, 1999). Consequently, the failure rate of new chemical entities (NCEs) due to absorption, distribution, metabolism, and excretion (ADME) shortcomings in clinical trials, in contrast to some of the other major hurdles including poor efficacy and intolerable toxicity, has continuously decreased (Apic et ah, 2005). 

Despite the positive results, these trials as well as four further non-randomized, controlled clinical studies [24-27] provide only limited evidence for the effectiveness of the tested preparations as methodological shortcomings cast some doubts on the reliability of the findings. Lack of blinding, unclear operationalization of clinical measurements and insufficient reporting make an independent judgement difficult. No trial on infectious diseases other than non-specific upper respiratory tract infections has been published since 1988. 

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