EMA addendum addresses vaccine development for immunocompromised people
The European Medicines Agency (EMA) has published a draft addendum to a guideline on vaccine development that encourages collecting clinical trial data on immunocompromised people in certain situations. The agency advised that when testing live vaccines, sponsors should wait to collect more safety and efficacy data on immunocompetent patients before evaluating immunocompromised patients.EMA noted that while the vast majority of vaccines won't be studied in immunocompromised patients, there may be situations when trials to evaluate the product in such people are necessary.
"In most cases it is expected that clinical trials in immunocompromised individuals will document the safety and immunogenicity of various test dose regimens, including the regimen considered suitable or already approved for immunocompetent individuals in the same age range," said the agency. "Such trials may include a control group of immunocompetent individuals or, with adequate justification and application of the same assay(s) to describe immune responses, a cross-study comparison with an immunocompetent cohort may be acceptable."
"In this way, trials can […] describe differences in safety and immunogenicity between groups of immunocompetent and immunocompromised individuals given the same dose regimen (i.e. that suitable for the immunocompetent); and […] compare the safety and immunogenicity data from these two groups with data obtained from groups of immunocompromised individuals randomized to receive alternative dose regimens," the agency added. "Alternative dose regimens may include one or more differences in amounts of antigen(s) per dose, number of doses and time intervals between doses."
EMA said that when planning a vaccine clinical trial in which immunocompromised subjects will also be assessed, sponsors should factor in the vaccine construct, its intended use, and other relevant information from similar vaccines when deciding how to conduct the trial and its timing. The agency also said that when evaluating live vaccines in a subset of immunocompromised patients, sponsors should delay their trial until there is enough safety and efficacy data on immunocompetent patients.
EMA acknowledged that studying a vaccine in every subset of immunocompromised patients is not feasible. Instead, it recommended that sponsors identify one or more subgroups of immunocompromised patients who may be enrolled in sufficient numbers for a trial and ensure the data collected can be adequately extrapolated.
"If the sponsor wishes to conduct a single trial in which immunocompromised individuals from more than one distinct subgroup are enrolled, consideration should be given to stratification according to the underlying reasons for immunodeficiency and/or pre-determined capping of numbers," said EMA. "In such cases, it may be appropriate that the primary analysis is based on all immunocompromised individuals, in which case descriptive analyses of data by defined subgroups should be planned."
EMA provided guidance on several other factors, such as statistical considerations when conducting the trials and evaluating the data and safety considerations.
The agency also noted the guidance's limitations. It stated that it does not address issues such as evaluating how common diseases associated with milder forms of immunodeficiencies may predispose patients to certain infections or developing vaccines only for immunocompromised patients or their subgroups.
EMA addendum
