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David Fram

Publications and source records attributed to David Fram.

5 recordsLinked to original sources
PubMed2006

Comparative performance of two quantitative safety signalling methods: implications for use in a pharmacovigilance department.

BACKGROUND AND OBJECTIVES: There is increasing interest in using disproportionality-based signal detection methods to support postmarketing safety surveillance activities. Two commonly used methods, empirical Bayes multi-item gamma Poisson shrinker (MGPS) and proportional reporting ratio (PRR), perform differently with respect to the number and types of signals detected. The goal of this study was to compare and analyse the performance characteristics of these two methods, to understand why they differ and to consider the practical implications of these differences for a large, industry-based pharmacovigilance department. METHODS: We compared the numbers and types of signals of disproportionate reporting (SDRs) obtained with MGPS and PRR using two postmarketing safety databases and a simulated database. We recorded signal counts and performed a qualitative comparison of the drug-event combinations signalled by the two methods as well as a sensitivity analysis to better understand how the thresholds commonly used for these methods impact their performance. RESULTS: PRR detected more SDRs than MGPS. We observed that MGPS is less subject to confounding by demographic factors because it employs stratification and is more stable than PRR when report counts are low. Simulation experiments performed using published empirical thresholds demonstrated that PRR detected false-positive signals at a rate of 1.1%, while MGPS did not detect any statistical false positives. In an attempt to separate the effect of choice of signal threshold from more fundamental methodological differences, we performed a series of experiments in which we modified the conventional threshold values for each method so that each method detected the same number of SDRs for the example drugs studied. This analysis, which provided quantitative examples of the relationship between the published thresholds for the two methods, demonstrates that the signalling criterion published for PRR has a higher signalling frequency than that published for MGPS. DISCUSSION AND CONCLUSION: The performance differences between the PRR and MGPS methods are related to (i) greater confounding by demographic factors with PRR; (ii) a higher tendency of PRR to detect false-positive signals when the number of reports is small; and (iii) the conventional thresholds that have been adapted for each method. PRR tends to be more 'sensitive' and less 'specific' than MGPS. A high-specificity disproportionality method, when used in conjunction with medical triage and investigation of critical medical events, may provide an efficient and robust approach to applying quantitative methods in routine postmarketing pharmacovigilance.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Using simulation to assess the sensitivity and specificity of a signal detection tool for multidimensional public health surveillance data.

The objective of the work described in this paper is to develop a means for characterizing the validity of an empirical methodology for detecting signals potentially related to complicated adverse event (AE) coding terms in multidimensional public health surveillance data. The signal detection tool under evaluation is the multi-item gamma Poisson shrinkage (MGPS) estimation program. We were interested in its potential application to passive surveillance system monitoring, to screen for 'signals' of complicated adverse event coding terms (AE terms) in complex and noisy data. The research was to design and produce a flexible and user-friendly utility for probabilistically defining complicated signals in a database, iterating large numbers of applications of the MGPS detection algorithm and establishing proportions of correct detection events. We sought to establish the specificity of the MGPS by developing a random background using a gradient that ranged from rigorous (but not very relevant) to relevant (but noisy). To establish the sensitivity, signals were defined based on recognized public health issues of interest (such as the introduction of a new vaccine into the population). Methods of representing a signal included a simple pair-wise association consisting of a new vaccine and one AE term, as well as a more realistic complex of multiple AE terms comprising a 'syndrome'. A web application has been developed to create and insert signals with user-defined probabilities in multiple iterations of simulated random background data. Three forms of simulated data based on the vaccine adverse event reporting system (VAERS) cumulative spontaneous database were defined to serve as background noise against which to contrast introduced vaccine adverse event signals: (1) completely random associations between vaccines and AE terms, (2) random associations of vaccine sets and AE term sets preserving naturally observed vaccine co-occurrences and AE term co-occurrences and (3) samples from the actual VAERS data as reported. Rates of detection by the MGPS algorithm can be established for specific signal patterns at varying probabilistic intensities in a choice of random background data forms. Knowing these rates is important for determining the degree of response to an MGPS signal detection event in 'live' data.

Computer Simulation↗
PubMed2004

Association of asthma therapy and Churg-Strauss syndrome: an analysis of postmarketing surveillance data.

BACKGROUND: Churg-Strauss syndrome (CSS), also known as allergic granulomatous angiitis (AGA), is a rare vasculitis that occurs in patients with bronchial asthma. The nature of the association of CSS with various asthma therapies is unclear. OBJECTIVE: This study investigated the associations of different multidrug asthma therapy regimens and the reporting of AGA (the preferred code for CSS in the coding dictionary for the Adverse Event Reporting System [AERS]) by applying an iterative method of disproportionally analysis to th AERS database maintained by the US Food and Drug Administration. METHODS: The public-release version of the AERS database was used to identify reports of AGA in patients receiving asthma therapy. Reporting of AGA was examined using iterative disproportionality methods in patients receiving > or =1 of the following drug classes: inhaled corticosteroid (ICS), leukotriene receptor antagonist (LTRA), short-acting beta(2)-agonist (SABA), or long-acting beta(2)-agonist (LABA). The Bayesian data-mining algorithm known as the multi-item gamma poisson shrinker was used to determine the relative reporting rates by calculation of the empirical Bayes geometric mean (EBGM) and its 90% CI (EB05 = lower limit and EB95 = upper limit) for each drug. Subset analyses were performed for each drug with different medication combinations to differentiate the relative reporting of AGA for each. RESULTS: A strong association was found between LTRA use and AGA (EBGM = 104.0, EB05 = 95.0, EB95 = 113.8) that persisted with all combinations of therapy studied. AGA was also associated with the ICS, SABA and LABA classes (EBGM values of 27.8, 14.6 and 40.4, respectively). However, the latter associations were mostly dependent on the presence of concurrent LTRA and, to a lesser extemt, oral corticosteroid therapy and became negligible (ie, EB05 < 2) for patients who were not receiving these concurrent treatments. CONCLUSIONS: Differences based on relative reporting were observed in the patterns of association of AGA with LTRA, ICS, and beta(2)-agonist therapies. A strong association between LTRA use and AGA was present regardless of the use of other asthma drugs.

Administration, Inhalation↗
PubMed2002

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.

Adult↗