Severity & preventability Assesment .pptx

Severity and seriousness assessment
Predictability and preventability assessment
According to M.pharm Pharmacology syllabus

1. SEVERITY AND SERIOUSNESS ASSESMENT, PREDICTABILITY AND PREVENTABILITY ASSESSMENT PRESENTED BY: BAISHALI CHAKRABARTY GUIDED BY: DR. JIGNA SHAH

2. 01 03 02 Table of contents 04 SEVERITY ASSESSMENT SACLE SERIOUSNESS OF ADRs PREVENTABILITY ASSESSMENT PREDICTABILITY ASSESMENT 05 06 CASE STUDY REFRENCE

3. INTRODUCTION The term severity is used describe the intensity of a medical event and is graded as minor, moderate, severe and lethal. In case of minor reactions, no antidote is required, therapy or prolongation of hospitalization would be sufficient. In case of moderate reactions change in drug therapy is required along with specific treatment and/or prolongation of hospitalization. The reactions that are life threatening such as liver failure, abnormal rhythm of heart and certain types of allergic reactions, or that result in persistent or significant disability or hospitalization, or cause a birth defect are considered as severe ADRs. Usually a severe reaction takes place in case of discontinuation of taking the drug and it must be treated immediately.

4. DEFINITIONS Adverse Drug Reaction : According to WHO Adverse drug reaction is defined as “A response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function”. Adverse Event : Adverse event is defined as “Any medical occurrence temporally associated with the use of a medicinal product, but not necessarily casually related”. Severity : It describes the extent to which the ADRs influence the everyday life of a patient’s. Seriousness: It is of an ADR is related to its life threatening nature & is defined as any untoward reaction to the medicinal product that may result in death and require patient hospitalization.

5. SEVERITY ASSESMENT SCALE Severity was evaluated according to the classification provided in two ways Hartwig’s Severity Assessment Scale Karch and Lasanga Severity scale Hartwig’s Severity Scale On the basis of severity of the suspended reactions, this scale can be divided into three categorized into 7 levels of severity by J Seigel and PJ Schneider: Level 1: In this level no change is needed in treatment with the suspected drug in case of ‘mild’ type reaction. Level 2: In this level, the ADR requires that the suspected drug to be withdrawn or changed . Antidote or other treatment is not required, and the patient does not require further hospitalization. Level 3: It is same as level 2 the only difference is that an antidote or other treatment was required. No increase in Length of Stay (LOS).

6. 4) Level 4: It is classified in two parts: Level 4(A) : The patient requires further hospitalization (at least for a day) because of level 3 reactions. Level 4(B) : The patient can be hospitalized due to ADR. 5) Level 5: In this level the product reactions may need an intensive care unit attention in the severe type of ADR. 6) Level 6: In this level the reactions may cause permanent harm to the patient. 7) Level 7: In this level the patient may be die directly or indirectly due to ADR. NOTE: Level 1&2 fall under mild category, level 3&4 under moderate and 5,6&7 fall under severe category.

7. QUESTIONNAIRE FORM TO MEASURE THE SEVERITY OF ADR BY HARTWIG 

8. Karch and Lasanga Severity Scale According to Karch and Lasanga severity was classified into minor Moderate Severe Lethal SEVERITY DESCRIPTION EXAMPLE Mild No antidote or treatment is required hospitalization is not prolonged. Some Antihistamines Drowsiness Opioids ; constipation Moderate A charge in the treatment, but no necessarily discontinuation if drug is required; hospitalization may be prolonged, or specific treatment may be required. Hormonal contraceptives: Venous thrombosis. NSAIDS: Hypertension & Oedema Severe ADR may be life threatening and requires immediate discontinuation of drug and specific treatment for ADR. ACE Inhibitors: Angioedema Phenothiazines: Abnormal heart rhythm. Lethal Contributes to patient’s death Acetaminophen over dosage 2) anticoagulants

9. Karch and Lasanga Severity Scale Mild : A mild adverse drug reaction refers to an undesirable effect that is typically transient and does not require specific intervention. The reaction may cause minimal discomfort or inconvenience to the patient but is not considered life-threatening or significantly harmful. Examples of mild ADRs include mild nausea, dizziness, or rash. Moderate : A moderate adverse drug reaction is more pronounced than a mild reaction but still falls short of being life-threatening or causing severe harm to the patient. It may require some form of intervention or treatment to alleviate symptoms or prevent further complications. Moderate ADRs may interfere with the patient's daily activities or require closer monitoring. Examples include moderate allergic reactions, gastrointestinal disturbances, or hematologic abnormalities. Severe : A severe adverse drug reaction is one that poses a significant threat to the patient's health and well-being, potentially leading to serious complications, hospitalization, or even death if not promptly addressed. Severe ADRs often require immediate medical intervention and may result in long-term consequences for the patient. Examples include severe anaphylaxis, cardiotoxicity, or organ failure.

10. Karch and Lasanga Severity Scale Fatal: A fatal adverse drug reaction is the most severe category and refers to an adverse event that results in the death of the patient. These reactions represent the most catastrophic outcomes of drug therapy and highlight the importance of rigorous pharmacovigilance and risk management strategies to prevent future occurrences. Examples include fatal drug-induced liver failure, fatal anaphylaxis, or fatal cardiac arrhythmias.

11. SERIOUSNESS OF ADRs The seriousness of any adverse drug reaction is associated with the life threatening nature of that adverse reaction. Seriousness in the context of ADRs typically refers to adverse events that have significant medical consequences, pose a threat to the patient's health, or result in severe outcomes. The determination of seriousness is based on various criteria, often defined by regulatory agencies such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). A serious adverse event or reaction is any untoward medical occurrence associated with the use of a medical product in a patient that at any dose. Seriousness in ADRs serves as a crucial criterion for assessing the impact of adverse events on patient health and guiding regulatory decisions and clinical practices. Prioritizing the identification, reporting, and management of serious ADRs is essential for ensuring the safe and effective use of pharmaceutical products in healthcare settings.

12. FDA Criteria for Seriousness Assessment: Death Life threatening Hospitalization Disability Permanent damage Congenital Anomaly/ Birth defect Requires Intervention prevent permanent damage/impairment. Naranjo Algorithm : It is used to determine adverse drug reaction probability.

13. Outcome of the above statements are: Death: Report if the patient’s death is suspected as being outcome of the adverse reaction. Life threatening: Report if the patient was at substantial risk of dying at the time of the adverse reaction or it is suspected that the use or continued use of the product would result in the patient's death. Hospitalization (Initial or Prolonged): Report if admission to the hospital or prolongation of a hospital stay results because of the suspected adverse reaction. Disability: Report if the adverse reaction resulted in a significant, persistent or permanent disability/ incapacity; (change, impairment, damage, or disruption in the patient’s body function/ structure, physical activities, or quality of life). Congenital Anomaly: Report if there are suspicions that exposure to a medical product prior to conception or during pregnancy resulted in an adverse outcome in the child ( birth defect). Medically Important Event or Reaction: Medical & scientific judgement should be exercised in deciding whether other situations should be considered serious such as important medical events that might NOT be immediately life-threatening or result in death or hospitalization but might cause danger to the patient or might require intervention to prevent one of the other outcomes as listed above.

14. NARANJO ALGORITHM The Naranjo Adverse Drug Reaction Probability Scale, commonly known as the Naranjo Scale, is used for assessing the probability or likelihood that an adverse drug reaction (ADR) is attributable to a specific medication. It was developed by Dr. Naranjo and colleagues and provides a structured approach to evaluating the causal relationship between a drug and an adverse event. The Naranjo Scale consists of a series of questions that consider various factors such as the temporal relationship between drug administration and the onset of the reaction, alternative explanations for the reaction, previous reports of the reaction with the same drug, and the presence of similar reactions when the drug is withdrawn or reintroduced. Based on the answers to these questions, a numerical score is assigned, which categorizes the likelihood of the adverse event being caused by the drug as definite, probable, possible, or doubtful.

15. NARANJO ADVERSE DRUG REACTION PROBALITY SCALE

16. Scoring ≥ 9 = definite ADR 5-8 = probable ADR 1-4 = possible ADR 0 = doubtful ADR Score Interpretation of Scores Total Score ≥9 Definite . The reaction (1) followed a reasonable temporal sequence after a drug or in which a toxic drug level had been established in body fluids or tissues, (2) followed a recognized response to the suspected drug, and (3) was confirmed by improvement on withdrawing the drug and reappeared on reexposure. Total Score 5 to 8 Probable . The reaction (1) followed a reasonable temporal sequence after a drug, (2) followed a recognized response to the suspected drug, (3) was confirmed by withdrawal but not by exposure to the drug, and (4) could not be reasonably explained by the known characteristics of the patient’s clinical state. Total Score 1 to 4 Possible . The reaction (1) followed a temporal sequence after a drug, (2) possibly followed a recognized pattern to the suspected drug, and (3) could be explained by characteristics of the patient’s disease. Total Score ≤0 Doubtful . The reaction was likely related to factors other than a drug.

17. PREVENTABILITY AND PREDICTABILITY OF ADRs

18. PREVENTABILITY ASSESSMENT OF ADR Preventability assessment of adverse drug reactions (ADRs) involves evaluating the extent to which an adverse reaction could have been avoided or minimized through appropriate interventions or measures. This assessment is crucial for improving patient safety, optimizing medication use, and reducing the burden of ADRs on healthcare systems. Some of the details are: 1. Identifying Preventable ADRs: The first step in preventability assessment is identifying ADRs that could potentially be prevented. This involves reviewing patient records, medication histories, and adverse event reports to determine if the adverse reaction was foreseeable and could have been avoided with appropriate measures. 2. Assessment Criteria: Various criteria and tools have been developed to assess the preventability of ADRs. Common criteria include: Temporal Relationship: Assessing whether the adverse reaction occurred shortly after initiation or modification of the medication, indicating a potential causal relationship. Dose-Response Relationship: Evaluating whether the adverse reaction correlates with the dose or duration of medication exposure.

19. Rechallenge: Considering whether re-administration of the medication resulted in recurrence of the adverse reaction, indicating a causal relationship. Known Risk Factors: Identifying patient-specific factors or drug interactions that increase the risk of the adverse reaction. Monitoring and Management: Assessing whether appropriate monitoring strategies were in place to detect and manage the adverse reaction. 3. Healthcare Provider Judgment: Preventability assessment often involves the subjective judgment of healthcare providers, including physicians, pharmacists, and nurses. They consider clinical knowledge, experience, and professional judgment to determine if the adverse reaction could have been prevented through different actions or interventions. 4. Types of Preventable ADRs: Preventable ADRs can be categorized into different types based on the underlying causes and contributing factors. These may include medication errors (e.g., incorrect dose, wrong route of administration), drug interactions, inappropriate prescribing (e.g., contraindicated medications, off-label use), lack of monitoring, patient non-adherence, and inadequate patient education. 5. Preventive Strategies: Once preventable ADRs are identified, preventive strategies can be implemented to minimize the risk of recurrence. These may include medication reconciliation, comprehensive medication review, medication therapy management, patient education and counseling, implementation of clinical decision support systems, and healthcare provider training on medication safety

20. 6. Quality Improvement Initiatives: Preventability assessment contributes to quality improvement initiatives within healthcare settings. By identifying preventable ADRs and implementing targeted interventions, healthcare organizations can enhance patient safety, optimize medication use, and improve overall quality of care. 7. Documentation and Reporting: It's essential to document preventability assessments and their outcomes for quality assurance and reporting purposes. This information can be used to track trends, identify areas for improvement, and measure the effectiveness of preventive strategies over time. Schumock and Thornton Preventability Scale: Preventability assessment scales are tools used to systematically evaluate the extent to which adverse drug reactions (ADRs) could have been prevented. These scales provide a structured framework for healthcare professionals to assess the preventability of ADRs based on specific criteria. While various preventability assessment scales exist, one commonly used scale is the Schumock and Thornton Preventability Scale.

21. According to Olivier “there is no gold standard for preventability assessment”. In fact, it is not easy to asses preventability; it is rather complicated. Schumock and Thornton proposed a number of criteria to be considered to assess preventability. Whether an ADR is preventable or not Schumock and Thornton proposed in 1992 that its answer would depend on the answers of the following seven questions. If the answer is ‘yes’ to one or more of these questions, the final answer would be yes, the ADR is preventable. The questions are; Was the drug involved in the ADR not considered appropriate for the patient’s clinical condition? Were the dose, route, and frequency of administration not appropriate for the patient’s age, weight, and disease state? Was required therapeutic drug monitoring or other necessary laboratory tests not performed? Was there a history of allergy or previous reactions to the drug? Was a drug interaction involved in the reaction? Was a toxic serum drug level documented? Was poor compliance involved in the reaction? On the basis of the answer to these questions ADRs can be classified into ‘preventable’ or ‘non-preventable’.

22. 1. Definite (Score 1): ADR occurred due to an error in medication administration or prescribing that should not have occurred given the current state of medical knowledge. Preventability is certain, and measures to avoid the ADR were not implemented. 2. Probable (Score 2): ADR is most likely due to an error in medication administration or prescribing that could have been reasonably anticipated and prevented. Preventability is highly probable, but there may have been limitations or barriers to implementing preventive measures. 3. Possible (Score 3): ADR may be due to an error in medication administration or prescribing, but preventability is uncertain. There is some possibility that preventive measures could have been taken to avoid the ADR. 4. Unlikely (Score 4): ADR is not likely due to an error in medication administration or prescribing. Preventability is unlikely, as there is no clear indication that preventive measures could have been implemented to avoid the ADR.

23. 5. Definitely Not (Score 5): ADR is not related to an error in medication administration or prescribing and could not have been prevented. Preventability is certain, as there was no opportunity to prevent the ADR. By using Schumock and Thornton Scale preventability of ADRs can be evaluated. Any answer of “yes” to any question in this scale proposes that the ADR might have been preventable. ADRs can be categorized as definitely preventable ,probably preventable or not preventable.

24. In tabular form the characteristics of preventable ADRs and/or ADEs in hospitalized patients with respect to certain common drugs or drug-groups are given below:

25. In 1994, Petersen proposed a scaling system for assessment of preventability of adverse events .This was based on the opinion of a panel of three physicians. In 2002, Oliver proposed a method for preventability assessment. It considered of three sets of questions; Related to patient, Related to drug, and Related to prescription. In 1996, Dartnell proposed six questions to measure the ‘avoidability’ related to drug therapy. The Questions proposed are; Was the suspected drug judged to be indicated or contraindicated? Was the dosage form used different from accepted recommendations? Had there been adequate monitoring? Had there been adequate counselling? Could an alternative or no drug therapy have been undertaken? Was admission likely regardless of the inappropriate use of drug therapy?

26. PREDICTABILITY ASSESSMENT Predictability assessment in the context of adverse drug reactions (ADRs) involves evaluating the likelihood or foreseeability of an adverse reaction occurring in response to a medication. This assessment is crucial in pharmacovigilance for several reasons: 1. Risk Management: Predictability assessment helps in identifying and managing potential risks associated with the use of medications. Understanding which adverse reactions are more likely to occur allows healthcare professionals to take appropriate precautions and monitor patients more closely. 2. Regulatory Compliance: Regulatory agencies require pharmaceutical companies to assess the predictability of adverse reactions during the drug development process. This information is essential for determining the safety profile of a medication and obtaining regulatory approval. 3. Patient Safety: Predictability assessment contributes to patient safety by enabling healthcare providers to make informed decisions about medication prescribing, monitoring, and management of adverse reactions.

27. 4. Public Health: Identifying predictable adverse reactions contributes to public health efforts by ensuring that medications are used safely and effectively, minimizing harm to patients, and maximizing therapeutic benefits. Here are some key aspects involved in predictability assessment: 1. Known Pharmacological Effects : Understanding the pharmacological properties of a medication is fundamental to predictability assessment. Certain adverse reactions may be directly related to the known pharmacological effects of the drug. For example, gastrointestinal side effects are common with non-steroidal anti-inflammatory drugs (NSAIDs) due to their mechanism of action. 2. Preclinical Data : Preclinical studies provide valuable information about the potential adverse effects of a drug. Animal studies help identify potential toxicities and guide dose selection for clinical trials. Predictability assessment involves extrapolating preclinical data to predict adverse reactions in humans.

28. 3. Clinical Trials : Clinical trials are essential for evaluating the safety and efficacy of medications in humans. During clinical development, adverse reactions are monitored and assessed for their predictability. The frequency, severity, and characteristics of adverse reactions observed in clinical trials inform the predictability assessment. 4. Drug Class Effects : Some adverse reactions are known to occur with certain drug classes or pharmacological groups. Assessing the predictability of adverse reactions involves considering the class-specific risks associated with a medication. For example, QT prolongation is a known class effect of certain antiarrhythmic drugs. 5. Patient Factors : Individual patient factors, such as age, gender, genetics, and underlying medical conditions, can influence the predictability of adverse reactions. Certain patient populations may be more susceptible to specific adverse reactions due to pharmacokinetic or pharmacodynamic differences. 6. Drug Interactions : Drug-drug interactions can alter the pharmacokinetics or pharmacodynamics of medications, leading to unpredictable adverse reactions. Predictability assessment involves evaluating potential interactions and their impact on the risk of adverse events.

29. 7. Post-Marketing Surveillance : Even after regulatory approval and commercialization, ongoing monitoring of adverse reactions through post-marketing surveillance is essential for assessing predictability. Real-world data from post-marketing reports help identify previously unrecognized adverse reactions and refine predictability assessments. TYPES OF PREDICTABILITY: Type A (Predictable): Extension of pharmacologic effect. Often predictable and dose dependent. Responsible for at least 30% of ADRs. E.g., anticholinergics and dry mouth. Type B (Unpredictable): Idiosyncratic or immunologic reactions. Rare and unpredictable. E.g., chloramphenicol and aplastic anemia , penicillin induced anaphylactic shock.

30. By the classification of ADRs predictability can be determined. Aronson classification was followed in this study according to which adverse drug reactions are classified into following six types: Type A: Augmented, dose-related. Type B: Bizarre, non-dose related. Type C: Chronic, dose and time-related. Type D: Delayed, time related. Type E: End of use, withdrawal reactions. Type F: Failure of therapy. Type A,C,D,E and F were assumed to be predictable in the current study, whereas Type B was unpredictable.

31. CASE STUDY BASED ON ADR 1) A 65-year-old male patient, Mr. Smith, presents to the emergency department with symptoms suggestive of an adverse drug reaction (ADR). He has been on multiple medications for various chronic conditions, including hypertension, diabetes, and osteoarthritis. As a healthcare professional, how would you assess the severity of the ADR using an Hartwig Severity Assessment scale?

32. Mild (Grade 1): Mr. Smith experiences mild symptoms that are bothersome but not significantly impacting his daily activities. For example, if he developed a mild skin rash or slight dizziness. Moderate (Grade 2): Symptoms are more pronounced, causing discomfort and interference with daily activities but not leading to significant impairment. For instance, if Mr. Smith develops moderate gastrointestinal upset or persistent headache. Severe (Grade 3): The ADR results in substantial impairment of daily activities, requiring medical intervention. This could include severe hypotension or hyperglycemia requiring hospitalization or significant medical management. Life-threatening (Grade 4): Mr. Smith experiences an ADR that poses an immediate risk to his life and requires urgent medical intervention to prevent serious outcomes. For example, severe anaphylaxis or profound hypoglycemia. Death (Grade 5): In the most severe cases, the ADR leads directly to Mr. Smith's death .

33. Application to the Case Study: Mr. Smith's presentation to the emergency department suggests a potentially serious ADR. The severity would need to be assessed promptly to ensure appropriate management. Assessing the severity involves evaluating the impact of the ADR on his health status, considering factors such as vital signs, laboratory results, and clinical symptoms. Depending on the severity of the ADR, appropriate interventions would be initiated, such as discontinuation of the offending medication, supportive care, or administration of specific antidotes. Continuous monitoring and reassessment of Mr. Smith's condition are crucial to ensure appropriate management and prevent further complications. By utilizing a structured severity assessment scale like the Modified Hartwig Scale, healthcare professionals can standardize the evaluation of ADRs, facilitating prompt recognition and management, ultimately improving patient outcomes.

34. 2) A 45-year-old female patient, Mrs. Johnson, presents to her primary care physician with symptoms suggestive of an adverse drug reaction (ADR). She has been recently prescribed a new medication for hypertension. How would you assess the preventability of the ADR in this case?

35. Definitely Preventable (Score 1): Mrs. Johnson experiences an ADR that could have been completely avoided if appropriate measures were taken. This may include prescribing a different medication or adjusting the dosage based on her medical history and risk factors. Probably Preventable (Score 2): The ADR could likely have been prevented with more careful monitoring or patient education. For example, if Mrs. Johnson had been informed about potential side effects and instructed to report any unusual symptoms promptly. Possibly Preventable (Score 3): Although less certain, there are still identifiable opportunities where the ADR could potentially have been avoided. This might involve closer monitoring of Mrs. Johnson's response to the medication or considering alternative treatment options. Not Preventable (Score 4): Despite all reasonable efforts, the occurrence of the ADR was unavoidable given the circumstances. This could occur if the ADR was an unexpected reaction or if Mrs. Johnson's medical condition necessitated the use of the medication despite the associated risks.

36. REFRENCES Parthasarathy G, Hansen k Nyfort, Nahata CM; A textbook of Clinial Pharmacy Practice; pg 89-97. Dr. Agnimitra Dinda, Monika Saxena; A textbook of Pharmacovigilance pg no 40-42. S.K. Gupta , Textbook of Pharmacovigilance. 2nd Edition , Jaypee Brothers Medical Publishers, 2019.

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