A multi-centric study for the validation of the SNG algorithm for causality assessment of adverse events

Adverse events (AEs) can cause increased morbidity, hospitalisation, and even death. It is essential to recognise AEs and to establish their correct causal relationship to a drug. Many causality assessment methods, scales and algorithms are available to assess the relationship between an AE and a drug. The Naranjo algorithm is most commonly employed in spite of many drawbacks as it is simple to use. However, improper assessment can lead to drug discontinuation and subsequently loss of drug efficacy. A recent study by Madhavi Murali and colleagues also have found that many questions were unanswered during the causality assessment of adverse events when the assessment is made using Naranjo scale. There are other causality assessment methods for assessing adverse events. The WHO and Naranjo causality assessment methods are generic in nature and their applicability in different situations has been time tested. There are certain issues in which each method has its own distinct identity. Keeping in mind the practical issues, some areas need to be revised in the causality assessment methods. Hence, we modified the existing Naranjo scale (NS) and developed the Sharma-Nookala-Gota – SNG, algorithm to address the shortcomings of NS. We have validated the SNG scale against the gold standard, physician’s opinion using the AEs data collected from the lung cancer patients who were on platinum-pemetrexed doublet. The SNG algorithm was found to have better concordance with the physicians’ causality assessment compared to the Naranjo algorithm. The SNG algorithm was found to have better concordance with the physicians’ assessment of causality compared with the Naranjo algorithm. The present study is a multicentric study aimed at validating the SNG algorithm in a larger cohort of patient and comparing its performance against the established scales for causality assessment. The participating centres along with Tata Memorial Centre, Mumbai are the Manipal Academy of Higher Education, Manipal and the PGIMER Chandigarh.

Eligible patients having an adverse event either in the out-patient departments or the wards and willing to give a written informed consent will be enrolled. Demographic details such as age, sex, height, weight, BSA, and baseline laboratory parameters will be documented. Reports of special investigations such as drug levels, if available, will be documented. Detailed information about the adverse event will be recorded in the CRF. Causality assessment of the event to the implicated drug or regimen will be assessed by designated personnel using the SNG, NS and WHO algorithms. Concordance of each causality assessment scale with the physician’s opinion will be estimated using the Kappa statistic. The sensitivity, specificity, PPV and NPV will also be determined.