Controlled clinical trials in cystic fibrosis — are we doing better?

Abstract

We have previously reported the time trends, design and interventions in randomised controlled trials (RCTs) in cystic fibrosis (CF) from 1961 through 1997 [Cheng K, Smyth RL, Motley J, O'Hea U, Ashby D, Randomised controlled trials in cystic fibrosis (1966-1997) categorized by time, design, and intervention. Pediatr Pulmonol 2000, 29:1-7.]. We maintain an ongoing register of all RCTs and controlled clinical trials (CCTs) in CF and have noted that in the five years since 1997 there has been a 48% increase in published trials. We aimed to assess whether this increase has been associated with an improvement in design quality. All RCTs and CCTs from 1961-2002 were assessed. Two epochs were then compared, 1961-1997 and 1998-2002. For each trial we recorded the design, participant numbers and the intervention studied. 261 trials in 1998-2002 were compared with 544 trials in 1961-1997. Comparing the two epochs a similar proportion of trials were parallel, double-blind and placebo controlled; also the median number of participants was similar. In the later epoch 25% of trials were multicentre, compared with 11% previously. Whilst this recent increase in clinical trials in CF is welcome, this has not been associated with improvements in quality. The trend for an increasing proportion of trials to be multicentre is encouraging. There are however, still deficiencies in the design of clinical trials in CF.

The Prognosis of Cystic Fibrosis - A Clinician's Perspective

“…However, evidence-based medicine has its limitations and possible stumbling blocks (Driever, 2002;Saarni et al, 2004;Miles et al, 2008;Shahar, 2008;Miles et al, 2011), in particular when it concerns diseases as complex as CF for which numerous therapeutic modalities have simply not yet been adequately studied (Cheng et al, 2000;David, 2001;Briggs et al, 2006;Kraynack et al, 2009). Best practice remains individualized in part, although a coherent foundation of evidence-based medicine is absolutely necessary.…”

Feasibility study to inform the design of a randomised controlled trial to eradicate Pseudomonas aeruginosa infection in individuals with Cystic Fibrosis

“…Although, a number of recent trials have addressed the benefits of existing therapies[10,11] and this picture is slowly improving[12], there are still considerable uncertainties about the effectiveness of many widely used, expensive and often invasive treatments for people with CF. CF patients and families are generally very well informed about their disease and its treatment, but this is the first study, of which we are aware, which has formally sought their views about acceptability of a proposed clinical trial.…”

Clinical trials in cystic fibrosis

“…As pharmacokinetics may be different in CF, phase I studies should be undertaken in people with CF before progressing to phase II. The size of clinical trials conducted in CF patients has often not been large enough to be able to answer important questions [128]. The Clinical Trial Network (CTN) (see Section 6) will insure that clinical trials are conducted in the best possible manner, involving a panel of European expert physicians, biostatisticians and scientists.…”