Clinical decisions in hepatology: the pirfenidone case analysis.

The approval of potentially effective treatments for serious and life-threatening conditions represents a particularly difficult arena for drug developers, regulators and physicians. Hanging in the balance is the need to provide a timely treatment alternative to an otherwise untreatable and serious condition, while also assuring that the proposed treatment is sufficiently safe to preserve the overall wellbeing of the patient. This is a particularly difficult decision, as weighting the risk and benefits must be done fast and over a much finer scale than in situations where effective treatments are available. Recently, the Federal Commission for the Protection against Sanitary Risk in Mexico (COFEPRIS) approved the use of pirfenidone for the treatment of lung and liver fibrosis (Register 154M2013). This is an important advance for patients with idiopathic pulmonary fibrosis, for which four randomized clinical trials of adequate quality, a meta-analysis and a cost-effectiveness analysis are available.1 However, some concerns remain as individuals participating in these clinical trials may not be wholly representative, the cost-efectivenes anaylisis could be uncertain for some subgroups, and stop rules could apply.1 Nonewithstanding, available data seems robust enough to use pirfenidone in lung fibrosis under careful surveillance. Pirfenidone’s use for liver fibrosis is not as certain. Despite some experimental data to confer biological plausibility,2 there are still no randomized blinded clinical trials to confirm the safety and efficacy of this drug. The information about its use in clinical practice is based in a case series with a small and underpowered sample size,3 and has not been replicated by other groups. Additionally, in a recent meta-analysis including 1,073 patients pirfenidone was associated with neurologic, gastrointestinal, and dermatologic adverse events, as well as with early termination of treatment (number needed to harm for discontinuation of 16; 95%CI 9.5-35.7).4 It is clear that the evidence supporting pirfenidone’s efficacy is scarce, compared to the evidence available regarding its potential side effects. Pirfenidone’s approval presents a unique opportunity to review the tenants that should direct the approval of a promissory drug for a severe and lifethreatening condition, as many important lessons could be learned. Translational medicine under serious and lifethreatening conditions. Translational medicine represents a switch in the paradigm of medical research.5 Under translational medicine the scientific community is expected to: