The path from the laboratory to the bedside is now far more complex than in past decades. The modern ethical framework for conducting research has created the necessary barriers to safeguard patient safety. Thankfully, no longer can clinicians simply take a drug under development and experiment it on patients, without evidence of its potential efficacy and safety data on its toxicology and teratogenicity.
The importance of full translational research in the workup of a therapeutic product is highlighted in the use of talc for pleurodesis [9, 10]. Millions of patients have received talc pleurodesis since the first report of talc poudrage in 1935 , even though talc has never been subjected to ‘proper’ laboratory workup and testing. Only half a century later was the observation made that talc could induce acute respiratory distress syndrome (ARDS). In subsequent studies, not only did researchers find impurities in many commercial talc preptions, they also discovered that talc particles were heterogenous in size within most products. Animal and human studies, including randomized trials, found that small talc particles are often systemically absorbed after their intrapleural delivery and induce lung inflammation and ARDS . Talc-induced respiratory failure can affect up to 9% of patients, and caused death in 2.3% of the 482 patients undergoing talc pleurodesis in a multicenter study . Clinical guidelines now recommend only the use of large particle size talc for pleurodesis .
On the other hand, there have been many significant successes in bringing laboratory discoveries to clinical care through proper translational research and regulatory channels. Conjugate pneumococcal vaccines, for example, have reduced the burden of disease in children and adults worldwide since their introduction . Anti-human immunodeficiency virus agents have prolonged life expectancy in HIV patients by decades, and the discovery of EGFR mutations in lung cancer have led to new therapies for those harboring such mutations. Understanding the pathogenesis of cystic fibrosis (CF) has led to the first successful introduction of a modulator of CF transmembrane receptor, albeit only for patients with a G551D mutation .