Access Programs and Studies

In open-label extension (OLE) studies, participants continue on the study drug to allow for long-term data collection at specific time points to meet health authority requests, support sponsor objectives or enhance understanding of the safety profile.

• These studies provide an opportunity to close multiple feeder studies, rolling patients into one OLE study. (Feeder study, or parent study, is the term for clinical trials whose patients transition into the OLE.)
• Of the options for continued access, OLEs provide an opportunity for the highest amount of data collection by having patients continue to follow a schedule of events that generally reduces burdens from feeder studies.

A sponsor may use the terms OLE and rollover synonymously. We make the distinction that OLEs are focused on continued long-term data collection (safety, efficacy, and/or tolerability), whereas rollovers are focused on continued patient treatment. A sponsor may also refer to an OLE as continued access, long-term extension or long-term follow-up.

Rollover studies continue treatment access post-feeder studies for patients who participated in a clinical trial, to allow continuity of therapeutic benefits.

• These studies may bridge the gap between the end of clinical trial participation and country-level product commercial availability/reimbursement, or they may provide product for a defined period if the product will not be made available in country.
• Patients follow standard of care for most procedures, and a reduced amount of data is collected, with a focus on safety data.

Note: A sponsor may refer to a rollover as an OLE, extended access program, continued access, long-term extension or long-term follow-up.

We use the term Expanded Access Program (EAP) to encompass all types of global regulatory pathways specifically designed for continued and early access to medicines.

EAPs allow manufacturers to provide an investigational product (drug, biologic or medical device) to treat or diagnose a patient with a serious or life-threatening disease or condition. In these cases, the patient does not have comparable or satisfactory alternative therapies available and cannot participate in a clinical trial, at the unsolicited request of a treating physician.

• The intent is patient treatment, but depending upon the country, there may be options for data collection.
• EAPs are typically used to “expand access” to treatment-naïve populations. There are recent regulations designed specifically for “continued access” for post-study patients via EAP mechanisms.

The term EAP is most used in the United States. There are more than 100 terms used worldwide, with some countries having more than one term for different types of programs (e.g., nominative vs. cohort). Most common terms include emergency use program, named patient program, compassionate use program, treatment-use protocol and post-study access program.

Changes to clinical trial regulations in specific countries (e.g., Portugal, Israel, Brazil) require sponsors to commit to continued provision of medication free of cost post-clinical trial closure.

• Select countries such as Brazil have designated post-trial access (PTA) regulatory pathways specifically for continued access for post-study patients. Other countries such as Portugal use existing EAP regulatory pathways rather than developing new pathways to achieve the same results of post-study access.
• While PTA programs have separate regulatory pathways from EAPs, the general requirements for approval are consistent with EAPs.
• PTA programs do not allow participation of treatment-naïve patients. The exception is patients who were part of a comparator arm within the clinical trial and now wish to access the investigational product. This exception is country- and regulation-specific.