upriya Desai, Director, Medical Safety Operations

Patient Reported Outcomes of Adverse Events (PRO-AEs) for Better PV Outcomes

Supriya Desai

The Patient-Reported Outcomes Safety Event Reporting (PROSPER) Consortium was convened to improve safety reporting by better incorporating the perspective of the patient. PROSPER comprises industry, regulatory authority, academic, private sector and patient representatives, interested in the area of patient reported outcomes of adverse events (PRO-AEs).

A PRO-AE is any untoward medical occurrence, whether or not considered treatment/intervention related, that is reported or transmitted directly by the patient without interpretation by a clinician or anyone else. This includes information from patients directly reporting their own experiences (e.g. symptoms) and from patients transmitting data that they have received (e.g. laboratory test results).

The PROSPER consortium has developed guidance on PRO-AE data, including the benefits of wider use and approaches for data capture and analysis. The guidance aims to ensure that the patient ‘voice’ and perspective feed appropriately into collection of safety data, so that safety profiles and hence benefit-risk balance of new and existing medicines is better defined. The guidance covers a minimum core data set for use by industry or regulators to structure PRO-AEs and how data, once collected, can be evaluated to drive safe and effective use of medicinal products. Structured collection of such patient data can be considered both a means to an end (improving patient safety) as well as an end in itself (expressing the patient viewpoint)(1).

PRO-AEs:Tools, Benefits and Challenges

Effective involvement of patients in the AE reporting process is possible by use of novel ADR reporting tools and processes like ADR online forms, mobile applications and through local pharmacies. Developing guidelines for the follow-up procedure for reports in consultation with patients’ and HCP organisations enables collection of high-quality data, conveys feedback to patients on how the information will be used and provides patients with further information or where information is available e.g. the publicly-accessible part of the EudraVigilance database(2).

Engaging patients as partners in the data collection enterprise can enable systematic collection of PRO-AEs and provide a more comprehensive picture within a population. This can be achieved in limited populations via patient registries, or in a wider population using existing infrastructure to engage patients e.g. community pharmacies and pharmacists(3).

The benefits of PRO-AEs are applicable across various stakeholders. Patients can know what to expect in terms of potential adverse events due to prescribed medications and also medication preferences, based on the prior experiences of other patients (“patients like me’’). Drug developers can understand how well patients will tolerate a product, particularly for oral therapies when compliance is strongly associated with symptomatic side effects. For regulators, a systematic, patient-reported approach would increase confidence in the fidelity of reported safety information toward balancing risks and benefits, provided reports are detailed and complete. Payers would be able to better understand the side effects of specific treatments to help predict the utilization of healthcare services and determine the benefit-risk balance (i.e. value) of medicines while HCPs can get valuable information based on an individual patient’s experience, which combined with the physician perspective based on experience and training provides a more accurate understanding of the patient’s symptoms, which helps improve measurement of symptoms in both clinical trials and practice(1).

On the other hand, there are potential public health downsides due to PRO-AEs being disseminated without the appropriate benefit-risk context, causing unnecessary alarm or leading to discontinuation of effective therapies. Other perceived disadvantages of PRO-AEs include costs, possibility of swamping safety signal with noise, exacerbation of the placebo effect at pre-approval phases and a significant risk of having duplicates in the database for cases received from multiple sources.

Final Thoughts

Despite all these changes and increased attention on the perceived value of PRO-AEs, their full potential is yet to be realized in PV. Current methods for safety reporting and risk assessment still rely heavily on HCPs though there are known limitations like under-reporting and discordant perspectives between patient and HCP reports. There seems to be a reluctance to adopt an approach that includes PRO-AEs due to multiple challenges.

How can we address regulatory constraints and concerns about feasibility, validity and reliability of using patient-reported AE data? How can we develop and methods and algorithms to review high data volumes without obscuring or reducing focus on key safety concerns? How do we best manage the added administrative requirements and costs? How do we overcome the limitations of the available questionnaires/methods? How can industry concerns about the potentially high volume of relatively ‘minor’ AEs reported by patients be addressed? What best practices and recommendations need to be implemented for managing data privacy issues, including control of patient information collected and stored electronically?

PV teams that address these challenges would be able to integrate PRO-AEs into their overall PV strategies towards incorporation of the patients’ “voice” in PV systems and processes. Such PV organizations are better positioned over the long term to ensure patient safety and add real value back to the patients by enhancing product benefit-risk profiles. Overall, adopting a patient-centric approach and partnering with patients and public for safety reporting and further analysis and communication of safety data clearly seems to be the way forward to better PV outcomes.


  1. Anjan K. Banerjee, Sally Okun, I. Ralph Edwards et al. Drug Saf (2013) 36:1129–114. Patient-Reported Outcome Measures in Safety Event Reporting: PROSPER Consortium Guidance.
  2. EPF Guidance on Pharmacovigilance. April 2012. Accessed Jun 28, 2015.
  3. Leone R, Moretti U, D’Incau P, et al. Effect of pharmacist involvement on patient reporting of adverse drug reactions: first Italian study. Drug Safety 2013 Apr; 36(4):267-76.