The comments come as the European Commission is deciding whether to adopt the act to amend the 2010 legislation and provide more clarity on situations in which PAES may be required to complement efficacy data. The majority of respondents -- including the federation, EMA and UK’s MHRA -- support the delegated act because it would “provide legal certainty, increase predictability and contribute to a focused dialogue” between regulators and MAHs.
The federation, meanwhile, seeks clarity from the Commission on scenarios when PAES would be voluntarily conducted and when they would be imposed on MAHs. The federation takes particular issue with observational or non-interventional studies and how the delegated act would respond to them, noting that German regulators claim this type of PAES does not exist because they are considered PASS (post-authorisation safety studies).
“There is more confusion around non-interventional or observational studies than around clinical trials,” the federation says. “Therefore, the scope of this delegated act should be widened and all possible scenarios should be covered.” The group also says the Commission should call studies “experimental” and “observational," rather than “interventional” and “not interventional” because the latter can be “strongly misleading.”
Non-interventional / observational studies are fundamental in evaluating a drug’s safety profile and identifying “hypotheses to be later validated by interventional / experimental studies,” the federation says, noting the example of comparing the collection of data “under real life conditions which subsequently will be compared with historic data from pivotal clinical trials.”
The EMA agreed with the federation, adding, “It is in the interest of public health to fully explore the potential added value of observational studies and pragmatic trials in the context of regulatory decisions.”
The EFPIA (European Federation of Pharmaceutical Industries and Associations) also called for the expansion of the delegated act’s scope, noting that it “considers the notion that PAES should always equal randomized clinical trials (RCT) is outdated and does not correspond to current expectations.”
Other Points of Concern
In addition, a separate section in the delegated act on data quality “may be a crucial point in the delineation between pre authorisation studies and PAES,” the CRO federation notes. “We also would welcome some discussion on the prevention of centre selection bias (e.g. whether centres should be identified by a random procedure).”
More details on the design and prerequisites for PAES -- such as protocol, sample size determination and data quality -- are also sought by the federation.