Early Detection Of Adverse Drug Reactions Research Articles

Application of artificial intelligence and machine learning in early detection of adverse drug reactions (ADRs) and drug-induced toxicity

Adverse drug reactions (ADRs) and drug-induced toxicity are major challenges in drug discovery, threatening patient safety and dramatically increasing healthcare expenditures. Since ADRs and toxicity are not as visible as infectious diseases, the potential consequences are considerable. Early detection of ADRs and drug-induced toxicity is an essential indicator of a drug's viability and safety profile. The introduction of artificial intelligence (AI) and machine learning (ML) approaches has resulted in a paradigm shift in the field of early ADR and toxicity detection. The application of these modern computational methods allows for the rapid, thorough, and precise prediction of probable ADRs and toxicity even before the drug’s practical synthesis as well as preclinical and clinical trials, resulting in more efficient and safer medications with a lesser chance of drug’s withdrawal. This present review offers an in-depth examination of the role of AI and ML in the early detection of ADRs and toxicity, incorporating a wide range of methodologies ranging from data mining to deep learning followed by a list of important databases, modeling algorithms, and software that could be used in modeling and predicting a series of ADRs and toxicity. This review also provides a complete reference to what has been performed and what might be accomplished in the field of AI and ML-based early identification of ADRs and drug-induced toxicity. By shedding light on the capabilities of these technologies, it highlights their enormous potential for revolutionizing drug discovery and improving patient safety.

Minireview of drug safety and pharmacovigilance

Pharmacovigilance or drug safety is defined as science and actions related to diagnosis, evaluation, understanding and avoidance of harmful effects or any other problems related to drugs. Adverse drug reaction (ADR) may be caused by intrinsic factors, extrinsic factors, underlying medical conditions, interactions and wrong usage. Adverse drug reaction (ADR) may be caused by intrinsic factors, extrinsic factors, underlying medical conditions, interactions and wrong usage. ADR causing intrinsic factors include the active ingredients in the drug itself. In Saudi Arabia, the National Pharmacovigilance Center (NPC) was established in March, 2009 as a semi-autonomous department of Saudi Food and Drug Authority (SFDA). The purpose of NPC was to perform early detection of ADR and safe use of drugs. We need pharmacovigilance because animal experiments and clinical trials performed before marketing are insufficient evidence of drug safety.

Profile of the adverse drug reactions among the multidrug resistant tuberculosis patients treated at a tertiary level hospital in southern India

Background: The prevalence of multi-drug resistant tuberculosis (MDR-TB) is increasing worldwide. The treatment of MDR-TB is challenging due to its delayed diagnosis, prolonged duration of therapy with larger number of drugs, coupled with their great potential for adverse drug reactions (ADRs), which severely impair treatment adherence. Early identification and effective management of ADRs form the cornerstone to ensure treatment adherence, which is an essential aspect in better treatment outcome. Materials and Methods: A prospective observational study was conducted for a period of 3 years, at Basaveshwara Medical College and Hospital, Chitradurga. All MDR-TB patients who fulfilled study criteria were included in study. After pre-treatment clinical evaluation, necessary radiological, serological and bacteriological investigations, patients were treated by Cat IV regimen for MDR TB and monitored for development of ADRs and treated appropriately. Results: Mean age of patients was 38 ± 3.6 years. A 70.9% of patients had low body mass index (BMI). A 74.5% of patients got successfully cured. ADRs were reported among 52.6% of patients. GI intolerance (49.1% in intensive phase) and psychiatric symptoms (41.8% in continuation phase) were most common ADRs reported. Low BMI was found to be significantly associated with ADRs. Conclusion: Meticulous and regular follow-ups with emphasis on early detection of ADRs during the course of ATT, dosage adjustments to effectively manage ADRs, addressing problem of malnutrition, a compulsory psychiatrist opinion as part of pre-treatment evaluation and also during continuation phase of ATT to detect the emergence of psychiatric symptoms, will go a long way in achieving high rates of favourable outcomes among MDR-TB patients. Keywords: Adverse drug reactions; Depression; Suicidal tendencies; Malnutrition; Gastro-intestinal intolerance.

Common causes and characteristics of adverse drug reactions in older adults: a retrospective study

BackgroundAging populations are often accompanied by comorbidity and polypharmacy, leading to increases in adverse drug reactions (ADRs). We sought to evaluate the causes and characteristics of ADRs in older Korean adults (≥65 years) in comparison to younger individuals (< 65 years).MethodsOf 37,523 cases reported at a Korean pharmacovigilance center from 2011 to 2018, we reviewed 18,842 ADRs of certain or probable causality on the basis of WHO-UMC criteria. We estimated the number of ADRs per 1000 patients exposed to the major culprit drugs, and incidence rate ratios were obtained to assess high- and low-risk medications in older adults.ResultsIn total, 4152 (22.0%) ADRs were reported for 3437 older adults (mean age, 74.6 years and 57.3% female). Tramadol (rate ratio, 1.32; 95% confidence interval [CI], 1.21–1.44; P < 0.001) and fentanyl (1.49, 1.16–1.92, P = 0.002) posed higher risks of ADRs in the older adults, whereas nonsteroidal anti-inflammatory drugs (NSAIDs) (0.35, 0.30–0.40, P < 0.001) and iodinated contrast media (ICM) (0.82, 0.76–0.89, P < 0.001) posed lower risks. Ratios of serious ADRs to NSAIDs (odds ratio, 2.16; 95% CI, 1.48–3.15; P < 0.001) and ICM (2.09, 1.36–3.21, P = 0.001) were higher in the older adults than in the younger patients. Analgesics primarily elicited cutaneous ADRs in the younger patients and gastrointestinal reactions in the older adults. ICM more commonly led to anaphylaxis in the older adults than the younger patients (3.0% vs. 1.6%, P = 0.019).ConclusionFor early detection of ADRs in older adults, better understanding of differences in the causes and characteristics thereof in comparison to the general population is needed.

Respiratory concerns of gabapentin and pregabalin: What does it mean to the pharmacovigilance systems in developing countries?

Gabapentin and pregabalin, commonly known as gabapentinoids, have been widely used globally. This paper highlights the serious breathing problems due to using gabapentin and pregabalin which was warned by the United States Food and Drug Administration on December, 2019. In this article, we tried to recommend suggestions for controlling these adverse drug reactions (ADRs). Safety reports of gabapentin and pregabalin should be obtained from concerned manufacturers and reviewed for respiratory depression effects. There should be strict prescription monitoring and drug use evaluation studies. Concurrent use of gabapentin and pregabalin with other respiratory depressants should be strictly monitored. Educating patients can help in the early detection of ADRs due to gabapentin and pregabalin. Anecdotal reports on these medications should be encouraged.

Treatment outcomes of drug-resistant pulmonary tuberculosis under programmatic management of multidrug-resistant tuberculosis, at tertiary care center in Mumbai

Background: This study was undertaken to analyze the clinical profile and treatment outcome in pulmonary drug-resistant tuberculosis (TB) patients under programmatic management of multidrug-resistant tuberculosis (PMDT) at a tertiary care center in Mumbai. Methodology: A retrospective study was conducted at PMDT site of a tertiary care hospital. The data of 194 pulmonary multidrug-resistant (MDR) TB patients diagnosed at our hospital or prediagnosed patients referred to our hospital were meticulously reviewed to study demography, baseline drug susceptibility to first- and second-line drugs, treatment outcomes, comorbidities, and adverse drug reactions (ADRs). Results: Out of 194 patients, 48.4% (68 cured + 26 treatment completed) were successfully treated, 22 (11.3%) failed on therapy, 39 (20.15%) patients died, 23 (11.8%) defaulted, 26 (13.4%) completed treatment with outcomes unknown, 13 (6.7%) were transferred out and in 3 patients (1.5%) treatment was stopped due to ADRs. Most common ADRs were gastrointestinal 32 (16.4%) and psychiatric 37 (19%). However, there was no statistical significance between the prevalence of ADRs and unfavorable outcomes. Most common comorbidities were GERD 27 (40.2%) and diabetes mellitus 22 (32.8%). Conclusion: Baseline drug susceptibility testing (DST) with rapid diagnostic tests, performing DST for second-line drugs, i.e., fluoroquinolones and aminoglycoside and modification of treatment regimen based on the same at start of MDR treatment has prime importance. Early detection of ADR's and comorbidities and their prompt treatment are also equally important.

A Retrospective Evaluation of Adverse Drug Reactions Due to Cancer Chemotherapy in a Tertiary Care Hospital in South India

Introduction: To evaluate the adverse drug reactions (ADRs) due to cancer chemotherapy in a tertiary care hospital in South India. Materials and Methods: This was a retrospective descriptive study. The data was obtained from patients who developed, at least, one ADR due to cancer chemotherapy during the period June 2014 to May 2015. The causality of the ADRs were evaluated by WHO-UMC causality assessment system and Naranjo’s ADR probability scale, the severity of ADRs were assessed by Hartwig and Siegel ADR severity assessment scale, and preventability of ADRs were determined by the Schumock and Thornton ADR preventability assessment scale. Results: One hundred fourteen ADRs due to cancer chemotherapy were reported in 73 patients. Hyponatremia (20.2%), neutropenia (11.4%), infections of the lung (11.4%), leucopenia (9.6%) were the commonly suspected ADRs. Cisplatin (62.3%), carboplatin (18.4%), cetuximab (3.5%), gefitinib (2.6%) were the commonly suspected medications. As per the WHO-UMC causality assessment system 66(57.8%) ADRs were possible and 48(42.1%) were probable. Naranjo’s ADR probability scale showed that 74(64.9%) ADRs were possible and 40 (35.1%) were probable. There was a very good agreement between the two scales (kappa=0.853). All ADRs were classified as level 4 severity barring one. None of the ADRs reported were preventable. Conclusion: Since 80% of the ADRs were suspected to be due to platinum containing anticancer drugs this provides a focus for further research on devising methods for prevention or early detection of ADRs. Prompt detection of ADRs is important to decrease morbidity and mortality. Key words: Adverse Drug Reaction, Cancer Chemotherapy, Causality assessment, Pharmacovigilance.

Evaluation of adverse drug reaction profile of antiretrovirals in HIV-positive patients in a tertiary care hospital

Background: Adverse drug reactions (ADRs) to antiretrovirals have been a matter of concern as they can affect patient compliance and treatment outcome. Hence, it is important to detect them early and institute appropriate treatment. Aims and Objective: To assess the prevalence, distribution, causality, severity, predictability and preventability of ADRs to antiretrovirals and to identify risk factors for their development in a tertiary care hospital in South India. Materials and Methods: This was a descriptive observational study. Data were collected from the case records of adult, treatment naive HIV-positive patients, newly initiated on antiretroviral drugs, January 2012 onward and closure of data set was on 31st December 2014. Results: A total of 238 cases met the inclusion criteria. Overall, 56 ADRs were noted. ADRs were observed in 39 males and 17 females. They were common in the age group 51-60 years. Anemia was the most common ADR followed by rash and hyperpigmentation. Most of the ADRs observed were of mild severity, requiring neither change in regimen nor any specific treatment. Zidovudine caused the highest number of ADRs, followed by nevirapine and stavudine. Most ADRs occurred within 6 months of starting antiretroviral therapy (ART). Causality relationship between drug and ADR was graded as “possible” according to WHO causality assessment scale. No statistically significant correlation of age, gender, weight, hemoglobin, CD4 count and the presence of opportunistic infections to the development of ADRs were noted. Conclusion: Regular monitoring, early detection of ADRs to antiretrovirals and their treatment is essential to optimize ART.

Development and Validation of Estimate Equations for Adverse Drug Reactions Using Risk Factors and Subjective Symptoms

The purpose of this study was to develop and validate estimate equations for preventing adverse drug reactions (ADRs). We conducted five case-control studies to identify individual risk factors and subjective symptoms associated with the following five ADRs: drug-induced ischemic heart disease; renal damage; muscle disorder; interstitial pneumonia; and leucopenia. We performed logistic regression analysis and obtained eight regression equations for each ADR. We converted these to ADR estimate equations for predicting the likelihood of ADRs. We randomly selected 50 cases with non-individual ADRs from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 65000 case reports of ADRs, and assigned these cases to a validation case group. We then calculated the predictive probability for 50 cases using the eight estimate equations for each ADR. The highest probability for each ADR was set as the probability of each ADR. If the probability was over 50%, the case was interpreted as ADR-positive. We calculated and evaluated the sensitivity, specificity, and positive likelihood ratio of this system. Sensitivity of the estimate equations for muscle disorder and interstitial pneumonia were ≥90%. Specificity and positive likelihood ratios of estimate equations for renal damage, interstitial pneumonia and leucopenia were ≥80% and ≥5, respectively. Our estimate equations thus showed high validity, and are therefore helpful for the prevention or early detection of ADRs.

Evaluation of awareness about pharmacovigilance and adverse drug reaction monitoring in resident doctors of a tertiary care teaching hospital

Adverse drug reactions (ADRs) are associated with significant morbidity and mortality and have a major impact on public health. Pharmacovigilance helps in early detection of ADRs and identification of risk factors. Underreporting of ADRs can be improved by imparting knowledge regarding pharmacovigilance to healthcare professionals. This study was aimed at investigating the knowledge and attitude of resident doctors about ADR reporting and suggesting possible ways of improving ADR reporting. This study was a cross-sectional, questionnaire-based survey conducted in a tertiary care teaching hospital. The respondents were resident doctors. Study instrument was a self-developed, pre-validated, semi-structured questionnaire consisting of open- and close-ended items. A total of 84 questionnaires were considered for analysis, giving a response rate of 93.33%. In all, 64.28% of the respondents were aware about pharmacovigilance, 52.38% were aware of ADR reporting system in India, 83.33% opined that only serious ADR with any medicine should be reported, and 35.72% believed that ADRs should be reported only for newly marketed agents. Although 67.85% of respondents observed an ADR, only 25% reported it; 44.04% were aware about the complete procedure of ADR reporting. General attitude of the respondents about ADR reporting was as follows: ADR reporting should be compulsory (15.19%), voluntary (41.66%), remunerated (3.57%), identity of prescriber should be concealed (21.42%), and identity of reporter should be concealed (29.7%). Increasing awareness about pharmacovigilance will be helpful in improving the status of ADR reporting. Other measures such as making ADR reporting guidelines available in the form of booklets and displaying posters can also play a useful role.

Lack of awareness of community-acquired adverse drug reactions upon hospital admission : dimensions and consequences of a dilemma.

Adverse drug reactions (ADRs) are a well-known cause of hospital admission. Nevertheless a quantitative estimate of the preventability of and physicians' awareness of these reactions is lacking. Using intensive bedside and computer-assisted drug surveillance methods a 13-month prospective pharmacoepidemiological survey was carried out on patients admitted to two medical wards of the Erlangen-Nuremberg University Hospital in Erlangen, Germany. This study aimed to define the incidence of preventable and unavoidable ADRs. In addition we investigated the awareness of the physicians to ADRs at the time of admission and the rate of contraindicated pre-admission prescriptions. In 78 (8.5%) of 915 (10.9%) admissions a total of 102 (42 preventable) community-acquired ADRs were detected on admission. In 45 (3.8%) of the admissions ADRs led directly to hospitalisation. 56.9% of the ADRs were not recognised by the attending physician on admission. Marked correlation was found between the awareness of ADRs and their probability and severity scores (r = 0.85 and r = 0.94, respectively; p < 0.05). The most frequently detected ADRs were due to direct toxicity and secondary pharmacological effects. Idiosyncratic reactions were often missed and 18.6% of all drugs prescribed prior to admission were contraindicated. Leading the list were diuretics, analgesics/NSAIDs and antipsychotics/sedatives. Awareness of existing ADRs on hospital admission and appropriate prescribing prior to hospital admission require attention. Early detection of ADRs on hospital admission can be achieved by the use of computer support systems. Many ADRs could be prevented by adhering to indications and contraindications.