The European Medicines Agency (EMA) has released a new guideline on clinical trials conducted to assess chronic obstructive pulmonary disease (COPD) products, updating an existing guideline regulators said had grown outdated.
Released 8 August, Guideline on clinical investigation of medical products in the treatment of chronic obstructive pulmonary disease is scheduled to come into effect on 1 September 2012 after more than two years in development. EMA officials said the guideline would replace a Points to Consider (PtC) document released in May 1999 of the same name.
EMA officials write the guideline builds upon the PtC document to reflect new scientific discoveries related to COPD, an irreversible narrowing of the airways leading to the lungs, and advances in clinical practice guidelines.
The new guidelines state sponsors should aim to assess COPD products in homogenous groups of patients with, "Mainly irreversible airway function, which would allow for better characterization of the effect of the drug."
"However it is accepted that up to 50% of patients with COPD do have some degree of reversibility of airflow obstruction and therefore some degree of freedom in respect of the inclusion of patients with differing degrees of airway reversibility, and the resultant need for sub-group analyses in respect of these differing degrees of airway reversibility, will be required," explained EMA. "Consistency of effect across such subgroups should be demonstrated."
If patients with a degree of reversibility are included, sponsors will need to show the effects of the drug would be applicable to those with irreversible declines in lung function as well, and that the impact of the drug was, "Not driven by this subset of patients."
The severity of the target population should be defined before the start of the trial using measures of "airflow limitation, symptoms, risk of exacerbation and presence of co-morbidities." EMA wrote.
All physical patient characteristics, including objective measures of the state of their COPD, should be recorded before the start of the trial. Other factors, including the patient's history of smoking or the patient's inclusion in a relevant sub-population, should be identified and recorded, officials said.
Assessing the Product
The guideline notes that different drugs developed for COPD will be aimed at different methods of combating the disease and should be assessed accordingly.
"Depending on the mechanism of action of the drug substance under evaluation, a complete characterization of the effect of any therapy in COPD would require the inclusion of a number of different variables belonging to those domains expected to be affected by the study drug, because most treatments will produce benefits in more than one area," explained EMA.
Those endpoints will include lung function, exacerbations and the severity of COPD, patient- and physician-reported outcomes, exercise capacity, composite scores based on airway obstruction, need for rescue medication, assessments by imaging and other endpoints such as biomarkers and physical activity.
European regulators also explained confirmatory trials using a comparator as a source of comparison were, "Difficult, as drugs with different modes of action and combinations of treatments are used in the management and treatment of COPD." Officials recommended the use of either a placebo and a comparator or just a comparator, though they were unlikely to accept the results of a trial using only a placebo as a comparison.
"The choice of the comparator will depend also on the severity of COPD and the type of study design," EMA explains in the guideline. "Ultimately, in the selection of the comparator, consideration must be given to current clinical treatment recommendations."
Regulators also cited their safety concerns regarding the drug class, noting the drugs are difficult to stop using once symptoms have been successfully managed. "Therefore a complete safety evaluation, as the primary safety assessment, is required for any treatment for COPD and required focus on the occurrence of adverse events for each individual component and adverse events known to occur with the particular combination of active drugs," wrote EMA in the guideline.
At least one year of safety data is required, with additional data preferred.