Cohort Definition Name : Earliest event of Myasthenia Gravis, inpatient, 2nd diagnosis or treatment, age gte 18
Contributor name : Mitch Conover’
Contributor OrcId :
Logic Description : Earliest occurrence of myasthenia gravis (excluding congenital, juvenile, neonatal or genetic) indexed on diagnosis date requiring either a second diagnosis of myasthenia gravis within 365 days after the first diagnosis (index date) or a drug exposure to Pyridostigmine on or 60 days after the first diagnosis or that the first diagnosis occur in an inpatient setting cohort exit is the end of continuous observation. Limit to persons with age greater than or equal to 18 on entry.
Recommended study application : target
Assertion statement : This cohort definition was executed on at least one real person-level observational health data source and resulted in a cohort with at least 1 person.
Target Clinical Description : Myasthenia gravis (MG) is a rare, heterogeneous, neuromuscular disease characterized by fluctuating, fatigable muscle weakness. Generalized myasthenia gravis (gMG) is characterized by the fluctuating and variable combination of weakness in ocular, bulbar, limb, neck, and respiratory muscles. Myasthenia gravis is caused by pathogenic autoantibodies directed against proteins in the postsynaptic membrane of the neuromuscular junction. In most patients (approximately 85% of cases), circulating antibodies target the acetylcholine receptor (AChR); to a lesser extent (<10% of cases), antibodies to the muscle specific kinase (MuSK), or lipoprotein-related protein 4 are present1,2.
"Evaluation conclusion : We developed a broad cohort definition requiring one-code for Myasthenia gravis (MG) using a concept set including 13 concepts for MG which incorporated what was found in the literature review, the PHOEBE analysis, and the orphan concepts within cohort diagnostics. We excluded patients that had genetic, congenital, or juvenile MG and restricted to those with ages >18. We performed the evaluation across a network of claim data sources and 1 EHR US data source. The data sources are: IBM® MarketScan® Commercial Database (CCAE), Optum’s longitudinal EHR repository (Optum EHR), Optum’s Clinformatics® Data Mart (DOD), IBM® MarketScan® Multi-State Medicaid Database (MDCD), IBM® MarketScan® Medicare Supplemental Database (MDCR), Japan Claims Database (JMDC), Clinical Practice Research Datalink (CPRD) , IQVIA® Australia Longitudinal Patient Data (LPD) database (Australia), IQVIA® Disease Analyzer (DA) France database (France), QVIA® Disease Analyzer (DA) Germany database (Germany), IQVIA® Adjudicated Health Plan Claims Data (formerly PharMetrics Plus) - US database (PharMetrics), IQVIA® Ambulatory EMR (EMR) . The algorithm retrieves subjects from all databases evaluated aside from IQVIA® Australia where too few subjects are identified. We evaluated drug eras for pyridostigmine which associated use is almost exclusive to MG. The inclusion of the concept set for pyridostigmine within the one-code definition increased the number of subjects included but resulted in lower positive predictive values (PPVs). These one-code definitions had improved sensitivities albeit at the expense of the PPVs as determined by PheValuator. There did not seem to be good coverage of many clinically relevant tests associated with MG within the cohorts, which was further complicated by several relatively non-specific signs and symptoms. Despite these factors, there was evidence for inconsistencies observed in the characteristics of the cohorts identified by the algorithms requiring one MG code representative of false cases. We tested algorithms utilizing provider specialty in conjunction with MG diagnosis and found that this significantly restricted the number of subjects making many databases then unsuitable for analysis. This also did not improve the performance characteristics. We developed a cohort definition requiring an initial inpatient diagnosis or post-index second code of MG 365 days after index. The cohort improved the PPV of the algorithm albeit at the expense of sensitivity as determined by PheValuator. We then evaluated pyridostigmine use associated with the initial inpatient diagnosis or post-index second code of MG 365 days after index. The inclusion of the concept set for pyridostigmine increased the number of subjects within the cohorts and improved the sensitivities in all databases evaluated although it produced slightly lower PPVs. We developed iterations of this cohort to evaluate different timeframes (365, 180, 90 days) for subsequent diagnosis to reduce potential opportunities for immortal time bias. The 365-day period was determined to improve sensitivity compared to a 180- or 90-day post-index second code requirement. Ultimately, the submitted definition resulted in acceptable values for sensitivity and positive predictive value in many of the databases evaluated and is recommended for use.
The incident versions of the definition (requiring continuous enrollment period 365 days before index) were evaluated using PheValuator sensitivity ranged from about 72% in EHR to about 94% in JMDC while positive predictive value ranged from 68% in MDCD to 91% in EHR.
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