As part of a series of post-marketing requirement (PMR) studies for extended-release (ER) and long-acting (LA) opioid analgesics, the Food and Drug Administration (FDA) is requiring New Drug Application (NDA) holders of ER/LA opioids to conduct studies to estimate the incidence of misuse, abuse, addiction, overdose, and death among patients with chronic pain using long-term opioid therapy, and to validate the measures used to estimate the incidence of these adverse events.
The purpose of this study is to validate the measurement of opioid overdose events using diagnostic codes and data extracted from notes written in the electronic medical record (EMR), accompanied by diagnostic algorithms, to be used in a study of the incidence and predictors of opioid overdose and death (PMR Study 1B) among patients prescribed opioid analgesics. Diagnostic codes, accompanied by diagnostic algorithms, will be compared against manually abstracted medical chart reviews.
Code-based algorithms will be useful for identifying opioid overdoses in claims-based systems that include only coded data and will also find applicability in systems with EMRs. Code-based algorithms will be improved with text search of EMR clinical notations using Natural Language Processing (NLP) to identify overdose events not identified by diagnostic codes and to differentiate between intentional and unintentional overdoses. Yield from the resulting EMR-based algorithm will again be compared against manually abstracted medical chart reviews.
This EMR-based algorithm will be useful for identifying opioid overdoses in systems with EMRs, and for further differentiating between the causes of different types of overdoses. For example, overdose events can be due to misuse (e.g., therapeutic use not as indicated by a clinician), medication errors by patients, medical errors made by prescribers, abuse by patients, abuse by non-patients feigning to be patients in order to receive medications; and suicides. Overdose events therefore differ in intentionality, that is whether the person was attempting suicide or not. Unintentional overdoses can occur as a result of various causes, including misuse (therapeutic use but not consistent with clinician orders), abuse, adverse reactions to medications, anesthesia, and medication errors-both patient and provider-based. In addition, the distinction between unintentional and intentional overdoses can sometimes be unclear. This validation study will attempt to differentiate overdose by intentionality using both code-based algorithms and NLP-enhanced algorithms.
Currently, administrative databases use ICD-9 codes for nonfatal diagnoses and ICD-10 codes for fatal events. In October of 2015, ICD-10 codes are scheduled to replace ICD-9 codes for nonfatal diagnoses in administrative databases. This study will validate existing ICD-9 codes so that the study can meet the FDA-required timeline for a final report by November 2015.
This study will not evaluate misuse since this will be captured by instruments in a prospective study of patients with chronic pain (PMR Study 1A) using a combination of adapted validated instruments, and new instruments that will be evaluated in PMR Study 2. This study will not include a formal validation for opioid-related deaths, since processes for coding deaths vary from state to state, but will include some verification of opioid-related deaths relative to medical records for events with available state and national death data (there is a 12-month to 2-year lag in state death records).
