A breach in patients' safety in randomized controlled trials of antibiotic drugs

Abstract

In a number of randomized controlled trials of antibiotic drugs the pathogens cultured from patients and their in vitro susceptibilities to the study drugs were not disclosed to the physicians during the whole course of the disease. These trials included patients with sepsis and bacteraemia. In clinical practice the information on the pathogen and its susceptibilities serves to re-evaluate the antibiotic treatment on the second or third day. As there is strong evidence that antibiotic treatment (empirical and definitive) matching the in vitro susceptibility of the pathogen reduces fatality rates in severe infections, withholding these data is a breach in patient safety. Sponsors and investigators of clinical trials of antibiotic drugs should ensure that the susceptibility of pathogens to the trial drugs are made available to clinicians in real time and taken into account when considering change in patient management, as would be the case in routine clinical practice. Members of research ethics committees should make sure that the protocols provide for this, while journals considering publication of clinical trial results should ask that details on the availability of susceptibilities to the trial antibiotics are disclosed in the methods section.

Developing a new antibiotic for extensively drug-resistant pathogens: the case of plazomicin

“…On the other hand, these trials must consider patient needs with respect to providing the optimal and safe treatment for patients included in these trials. Susceptibility testing for new antibiotics must be available on site and performed in real time [10].…”

Optimizing patient recruitment into clinical trials of antimicrobial-resistant pathogens

“…The syndromic approach may risk recruiting patients who do not actually have the disease of interest, or allow the recruitment of patients with an organism that is non-susceptible to the study drug. 13 Post-susceptibility exclusions could be used to resolve this problem, but will be limited by wasting resources and will risk imbalance between groups. Finally, bacteraemia, the most definite severe bacterial infection, was not well represented in syndrome-based trials compared with pathogen-focused trials (Table S2 , available as Supplementary data at JAC-AMR Online).…”

Systematic reviews and meta-analyses in infectious diseases: topics that merit special attention

“…Safety of included patients is probably the most important ethical aspect. For example, we have shown that in some clinical trials of antibiotic treatment the in vitro susceptibility of pathogens to the study drugs was not disclosed to the attending physicians in real time, even for septic patients .…”