Recommendations for achieving interoperable and shareable medical data in the USA.

Easy access to large quantities of accurate health data is required to understand medical and scientific information in real-time; evaluate public health measures before, during, and after times of crisis; and prevent medical errors. Introducing a system in the USA that allows for efficient access to such health data and ensures auditability of data facts, while avoiding data silos, will require fundamental changes in current practices. Here, we recommend the implementation of standardized data collection and transmission systems, universal identifiers for individual patients and end users, a reference standard infrastructure to support calibration and integration of laboratory results from equivalent tests, and modernized working practices. Requiring comprehensive and binding standards, rather than incentivizing voluntary and often piecemeal efforts for data exchange, will allow us to achieve the analytical information environment that patients need.

Profiling cumulative proportional reporting ratios of drug-induced liver injury in the FDA Adverse Event Reporting System (FAERS) database.

BACKGROUND: Early prediction and accurate characterization of risk for serious liver injury associated with newly marketed drugs remains an important challenge for clinicians, the pharmaceutical industry, and regulators. To date, a biomarker that specifically indicates exposure to a drug as the etiologic cause of liver injury has not been identified. OBJECTIVES: Using cumulative proportional reporting ratios (PRRs), we investigated 'real-time' profiles of a set of pharmaceuticals, over the first 3 years of US marketing, for the signaling of clinically serious drug-induced liver injury (DILI) in a large spontaneous-reporting database. METHODS: Using report counts of hepatic failure or clinically serious liver injury obtained from the FDA Adverse Events Reporting System (FAERS) database, PRRs of adverse drug event terms were calculated by division of counts of domestic reports of these events by counts of all serious adverse events for each of 13 selected drugs associated with a broad range of hepatotoxic risk (including three linked to only rare instances of clinically apparent liver injury) with reference to all other drugs in the database. Drug-specific cumulative PRRs were measured at successive intervals (calendar quarters) using cumulative tallies of FAERS reports to generate time-based profiles over the initial 3 years of US marketing. RESULTS: In the set of drugs analyzed, those with no known hepatotoxic risk demonstrated time-based cumulative PRR profiles that approximate the background rates of hepatic failure and serious liver injury reported in the entire FAERS database. In contrast, those that were removed from marketing or subjected to marketing restrictions due to their potential to cause liver injury were associated with profiles of rapidly rising cumulative PRRs that were greater than 5 within the first 10 million domestic prescriptions or the first four quarters of US marketing. The systematic tracking and identification of rising PRRs for DILI associated with newly marketed pharmaceutical and biological agents is a valuable tool for identification of safety signals within the FAERS database. LIMITATIONS: Disproportionality profiling of spontaneous reports in FAERS (e.g., cumulative PRR measurements), which signals an association between a recently marketed drug and liver injury, is not a method to quantitatively measure drug-related risk. Regulatory actions in response to emerging drug safety concerns often depend on an accurate assessment of risks using multiple sources of data and the consideration of overall benefits and risks of the agent. Causality must be determined through analysis of individual cases to exclude other etiologies of liver injury. CONCLUSION: The FAERS database can be used to advance empiric hepatotoxicity time-trending reporting levels for newly marketed agents in order to rapidly identify recently launched potential hepatotoxic agents and initiate further evaluation.

Atypical antipsychotics and pituitary tumors: a pharmacovigilance study.

STUDY OBJECTIVE: To analyze the disproportionality of reporting of hyperprolactinemia, galactorrhea, and pituitary tumors with seven widely used antipsychotic drugs. DESIGN: Retrospective pharmacovigilance study. DATA SOURCE: United States Food and Drug Administration's Adverse Event Reporting System (AERS) database. INTERVENTION: We initially identified higher-than-expected postmarketing reports of pituitary tumors associated with risperidone, a potent dopamine D2-receptor antagonist antipsychotic, by analyzing reporting patterns of these tumors in the AERS database. To further examine this association, we analyzed disproportionate reporting patterns of pituitary tumor reports for seven antipsychotics with different affinities for blocking D2 receptors: aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and haloperidol. MEASUREMENTS AND MAIN RESULTS: To conduct both of these analyses, we used the Multi-item Gamma Poisson Shrinker (MGPS) data mining algorithm applied to the AERS database. The MGPS uses a Bayesian model to calculate adjusted observed:expected ratios of drug-adverse event associations (Empiric Bayes Geometric Mean [EBGM] values) in huge drug safety databases. The higher the adjusted reporting ratio, or EBGM value, the greater the strength of the association between a drug and an adverse event. Risperidone had the highest adjusted reporting ratios for hyperprolactinemia (EBGM 34.9, 90% confidence interval [CI] 32.8-37.1]), galactorrhea (EBGM 19.9, 90% CI 18.6-21.4), and pituitary tumor (EBGM 18.7, 90% CI 14.9-23.3) among the seven antipsychotics, and one of the highest scores for all drugs in the AERS database. Some tumors were associated with visual field defects, hemorrhage, convulsions, surgery, and severe (>10-fold) prolactin elevations. The EBGM values for risperidone for these adverse events were higher in women, but high EBGM values for these events were also seen in men and children. Moreover, the rank order of the EBGM values for pituitary tumors corresponded to the affinities of these seven drugs for D2 receptors. CONCLUSION: Treatment with potent D2-receptor antagonists, such as risperidone, may be associated with pituitary tumors. These findings are consistent with animal (mice) studies and raise the need for clinical awareness and longitudinal studies.

Comparative study of electronic vs. paper VAS ratings: a randomized, crossover trial using healthy volunteers.

The visual analogue scale (VAS) is an established, validated, self-report measure usually consisting of a 10 cm line on paper with verbal anchors labeling the ends. Palmtop computers (PTCs also known as personal digital appliances) have incorporated VAS entry by use of a touch screen. However, the validity and psychophysical properties of the electronic VAS have never been formally compared with the conventional paper VAS. The aim of this study is to determine the agreement between the electronic (eVAS) and paper (pVAS) modes. Twenty-four healthy volunteers were recruited for this study. Each study participant provided input using both measurement methods by marking the eVAS and pVAS in response to two kinds of stimuli, cognitive and sensory. A verbal rating scale of seven descriptors of intensity represented the cognitive stimuli. Participants were asked to mark the location that best corresponded to the pain intensity described by each word on scales from 'no pain' to 'worst possible pain'. The sensory stimuli used were a set of test weights consisting of plastic containers ranging from 7 to 129 g. The VAS for sensory stimuli ranged from 0 (no weight) to 'reference weight' (the heaviest weight outside the range of test weights). There were two types of input stimuli and two modes for recording responses for a total of four experimental conditions. Two evaluators independently measured and recorded all the pVAS forms to the nearest millimeter. A total of 2016 stimuli were rated. The overall correlation for ratings of both sensory and cognitive stimuli on eVAS and pVAS was r = 0.91. For paired verbal stimuli the correlation was r = 0.97. For paired sensory stimuli the correlation was r = 0.86. The correlation between group eVAS and pVAS ratings to common verbal stimuli was r = 0.99. For common sensory stimuli the group correlation was r = 0.99. The median of correlations comparing eVAS and pVAS ratings was 0.99 for verbal stimuli and 0.98 for sensory stimuli. Multivariate analyses showed equivalent stimuli to be rated much the same whether entered on paper VAS or PTC touch screen VAS (P < 0.0001). Support was found for the validity of the computer version of the VAS scale.

Electronic diaries for monitoring chronic pain: 1-year validation study.

Electronic data collection for monitoring pain has become increasingly popular in clinical research. However, no direct comparison has been made between electronic diaries and self-report paper diaries or phone interviews. We asked 36 patients with chronic low back pain to monitor their pain for 1 year; 20 of them used both a palmtop computer and paper diaries, and 16 used paper diaries alone. All patients were called once a week and asked to rate their pain. Regression analyses with a measurement error model were run on hourly pain scores recorded by both palmtop computer and paper diaries. Ratings of pain intensity were highly reliable between data recorded with a palmtop computer and with data from paper diaries. Patients who monitored their pain with the palmtop computer entered data on average 6.75 times a week and were 89.9% compliant with daily monitoring throughout the year. Two-way messaging available through the palmtop computer seemed to encourage continued use of the device. Internal consistency of reporting and correlations with phone reports and standardized measures were highly significant, suggesting that data from electronic diaries are both reliable and valid. Patients using electronic diaries preferred them to paper diaries and showed much higher rates of compliance and satisfaction over the 1-year trial.