News Updates

More than 15 years ago, the CIOMS V Working Group observed that, “The recent widespread use of special post-marketing programs, such as drug compliance support or surveys, in which patients may be contacted routinely, has blurred the line between true spontaneous reports and what have become known as ‘‘solicited’’ reports from patients…” The primary goal of these programs is to engage individual stakeholders and, ultimately, to enhance the customer experience.

Since the CIOMS V Report was issued, these “Customer Engagement Programs” (CEPs) have evolved dramatically, with a broad range of goals, designs, conduct, and potential value to patients. Examples of CEPs for marketed biopharmaceutical products include patient support programs, market research programs, disease management programs, and product access programs, etc. These programs are rarely designed to capture either efficacy or safety data; thus, safety data derived from the vast majority of CEPs are considered “incidental” to the primary purpose of the program. This article sounds a call to action for the pragmatic and rational application of technology and regulatory science to safety data from CEPs.

The CIOMS V Report indicates that, “Incidental events should not ordinarily be the subject of expedited or periodic safety reporting. They should be captured as medical history or concurrent conditions and therefore retrievable at a later date if necessary, but should not be described as suspected ADRs on which reporting decisions are based.” Nevertheless, EU regulatory guidance categorizes incidental adverse events from any organized data collection scheme as solicited and indicates, “For the purpose of safety reporting, solicited reports should be classified as study reports, and should have an appropriate causality assessment, to consider whether they refer to suspected adverse reactions and therefore meet the criteria for reporting.” Thus, appropriate interpretation and handling of ‘‘incidental’’ events present conflicting challenges, particularly with regard to regulatory reporting.

To focus on truly important safety information from CEPs, regulatory science should evolve with due consideration of the following principles:

• All CEPs are not created equal and a single approach to evaluating safety information merits reconsideration
• When the intent and design of the CEP support active collection of safety information, a causality assessment should be performed on valid Individual Case Safety Reports (ICSRs)
• When the intent and design of the CEP do not include an organized safety data collection scheme and safety information is not actively solicited, implied causality of valid ICSRs should be assumed (as with spontaneous reports)
• When the CEP has multiple channels for reporting safety information, valid ICSRs should all be considered spontaneous reports, regardless of channel, unless the intent and design of each and every channel represents an organized safety data collection scheme; in the latter case, a causality assessment should be performed on all valid ICSRs
• “Grey Zone” CEPs, those not designed as organized safety data collection schemes but which may occasionally produce incidental information related to safety, do not ordinarily result in valid ICSRs that impact product benefit-risk assessment. “Grey Zone” programs might generate data from open-ended interview questions, such as, “Have you been feeling tired?” Unless the response expands to include safety information that can be classified as a serious event, responses to such questions should not be considered either for entry onto the safety database or for regulatory reporting (ICSRs or in the aggregate)
• For all programs where causality assessments are recommended, the focus should be on suspected serious unexpected adverse events, not all suspected adverse events.

CEPs have an important role in contributing to appropriate use of biopharmaceutical products and enhancing the patient experience. However, the ever-increasing volume of safety data now being generated by CEPs contributes to product benefit-risk in uncertain ways. Indeed, CEP-originated safety data could have the unintended consequence of obscuring or delaying recognition of real safety concerns that arise from other sources. This begs for novel approaches to ICSR detection and handling. For example, to address the high volume of safety data that must be screened, development of natural language processing, along with ontologic semantic reasoning, has the potential to improve business efficiency without compromising the need for due diligence in reviewing safety information from all sources.

In conclusion, all CEPs are not created equal. This is a call to action for the advancement of regulatory science to consider a risk proportionate approach to efficiently glean meaningful safety insights from CEPs.

References available upon request.