Conducting a clinical trial to investigate treatment of lung diseases such as idiopathic pulmonary fibrosis (IPF) is no small feat. Not only must pharmaceutical and biological companies enroll enough participants to reach statistical significance when making conclusions, but also they must adhere to increasingly stringent regulatory requirements. One way to more easily cross these hurdles is to conduct a multi-center international clinical trial, where a sufficient number of patients can be recruited in a relatively short period of time. However, as companies such as Boehringer Ingelheim know, many obstacles must be overcome when conducting these trials, such as ethnic differences in response to treatment.
This point was recently illustrated in the study “Essential Rules and Requirements for Global Clinical Trials in Rare Lung Diseases: A Sponsor’s Standpoint,” which was published in Respiratory Investigation. Boehringer Ingelheim has managed large international clinical trials that include International Study of Survival Outcomes in Idiopathic Pulmonary Fibrosis with Interferon Gamma-1b (INSPIRE) for IPF and Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) for chronic obstructive pulmonary disease (COPD). While UPLIFT was a successful clinical trial, the phase 3 INSPIRE trial could not confirm the results of efficacy seen in previous phases of clinical trials in patients with mild-to-moderate lung function impairment.
Perhaps one reason for unexpected results during international trials is the heterogeneity of patients’ responses to medication based on their ethnic backgrounds. Patients of different ethnicity have different pharmacokinetics and pharmacodynamics parameters, which alter the way drugs are distributed and used throughout the body.
To manage these differences, the Food and Drug Administration issued International Conference on Harmonization E5 guidance that gives recommendations for appropriately regulating clinical trials that consider a range of ethnicity. Largely, the recommendations emphasize that any investigated drug should be classified as sensitive or insensitive to ethnic factors to accordingly design and interpret trials.
However, these guidelines can be particularly difficult to follow when dealing with rare lung diseases such as IPF that remain somewhat poorly understood or defined. “There is considerable variability in diagnosis and management of rare lung diseases,” stated the article. “This may translate into difficulties in designing appropriate study protocols and standardizing all relevant elements of the study, including well-defined diagnostic, inclusion, and exclusion criteria, and suitable endpoints. This variability also poses major challenges to the study׳s execution.”
Two additional hurdles for conducting clinical trials on rare lung diseases is the low number of study centers with expertise in treating these conditions and the challenge of monitoring patient safety. Boehringer Ingelheim has dealt with these hurdles by establishing a steering committee for support and advice in planning global IPF trials. By closely following recommendations for clinical trials, the company continues to conduct quality research that benefits the lives of many individuals with rare lung diseases.