Case Reports: Evidence and Significance

Hierarchy of Evidence and Significance

• Case reports and case series rank low on the evidence hierarchy and aren't considered high-quality evidence.
• These reports can lead to regulatory actions by the FDA.
• They provide foundational background for hypothesis generation for more robust studies like observational studies or RCTs.

Case Reports: Definition and Characteristics

• Case reports are concise accounts of clinical characteristics, typically from a single patient, or a clinical course.
• A comparator or comparison groups are not part of the study design.
• They do not lead to conclusions or answer specific hypotheses but are purely descriptive.
• Case reports fall under the descriptive category of study designs, focusing on storytelling without making inferences.

Types of Case Reports

• Disease Identifications: Describe previously unknown aspects or variant forms of diseases.
• Adverse Drug Reaction Reporting: Crucial for pharmacists, reporting rare or severe reactions, which can lead to drug removal from the market; pre-marketing trials may miss rare adverse drug reactions due to limited sample sizes.
• New Treatment Approach: Describe new combination therapies, off-label uses, or applications in new populations, to generate hypotheses for future testing, sharing outcomes without causal inferences.
• Educational: Improve clinical practice through educational descriptions of patient interactions and insights.
• Quality Assurance: Describe events like practice or medication errors and the lessons learned.

Case Series: Definition and Characteristics

• Case series involve a group of patients sharing a similar characteristic, telling a story about that group.
• No comparison group is included.
• The series is descriptive.

Importance of Publishing Case Reports and Case Series

• They are essential for unexpected associations between diseases or symptoms.
• Unexpected events during patient observation or treatment should be reported.
• Publication helps shed light on the possible pathogenesis of disease or adverse effects, such as previously unreported ADRs or drug-drug interactions.
• Unique or rare disease features, as well as novel therapeutic approaches like off-label use or treatments in different populations, are worth publishing.
• Focus on "multicolor zebras" – weird, unusual, extremely rare cases.

Strengths of Descriptive Studies (Case Reports and Case Series)

• Primary strength lies in generating testable hypotheses, motivating further research.
• Help identify and disseminate information on rare, novel, or unique events in medical literature.
• Require minimal resources and are not very expensive or time-consuming to publish.

Weaknesses of Case Reports and Case Series

• Causal inferences cannot be made due to the absence of a comparison group.
• Reporting bias may be present.
• Data collection may be incomplete due to the retrospective nature, leading to potential time lags and missing data.
• Publishing has declined in recent years.

Journal Perspectives on Case Reports and Case Series

• "American Journal of Health-Systems Pharmacy (AJHP)" publishes case studies or series (up to 2,500 words) focusing on unusual drug reactions, pharmacotherapy-related issues, or valuable teaching information.
• Journals specializing in specific disease states are more inclined to publish case reports.
• "Pain Medicine" rarely publishes case reports/series, except for transformative or unique cases.
• "JAMA" rarely publishes case reports.
• Journal editors seek truly novel and unusual cases ("multicolored zebra").

Considerations for Publication

• Journal editors ensure protected health information is not disclosed.
• Patient consent forms may be required before the review process.

Guidelines for Writing Case Reports: The CARE Guidelines

• CARE (CAse REport) guidelines serve as a good starting point.
• Titles should include "case report".
• Abstracts can be structured (predefined sections) or unstructured (single paragraph).
• Introduction: Focus on the uniqueness of the case and provide relevant background information.
• Patient Information: Must be de-identified.
• Clinical Findings: List the diagnosis and physical findings.
• Timeline: Show the sequence of key events.
• Diagnostic Assessment: For pharmacy-related reports, discuss the algorithm used to assess drug causality.
• Therapeutic Intervention: Provide complete medication information (drug exposure).
• Follow-up and Outcomes: Note the patient's outcome after the intervention and lessons learned.
• Discussion: Review the relevant medical literature that makes the case report unique and discuss lessons learned.

Example of a Case Report

• Authors should avoid arguing for causality in the conclusion.

Preparing a Write-up for a Case Series

• Although there are no specific guidelines like the CARE guidelines, many principles still apply.
• Describe the setting where patients were recruited or received care.
• Describe inclusion and exclusion criteria.
• Consider how to display patient data individually or in aggregate form.
• Note potential conflicts of interest and funding sources.

Statistics in Case Series

• Commonly reported statistics include frequencies, mean, medians, standard deviation, etc..
• Descriptive statistics describe the population or sample without causal inference making.

Examples of Data Presentation in Case Series

• Case series report demographic characteristics at the individual or aggregate level.

Checklist for Evaluating Case Reports and Case Series

• Uniqueness: Requires searching the literature for similar studies and discussing findings.
• Documentation: Assesses whether sufficient information allows for evaluation.
• Educational Value: Evaluates the case report's value for clinicians, not too weird to be applicable.
• Interpretation: Assesses whether conclusions are supported by the information provided.
• Objectivity: Examines unbiased reporting and inclusion of all pertinent information.

Reporting of Adverse Drug Events: FDA MedWatch Program

• The FDA MedWatch reporting program captures information on unexpected side effects or adverse events from medications, product quality problems, and product use issues (medication errors, therapeutic failures, lookalike and soundalike medications).
• The MedWatch website contains links for health professionals and consumers/patients.

Products Reported Through MedWatch

• Reports to MedWatch involve products regulated by the FDA.
• Tobacco and e-cigarettes: Reported through the Safety Reporting Portal (SRP).
• Vaccines: Reported to the Vaccine Adverse Event Reporting System (VAERS).
• Animal products: Reported to the Center for Veterinary Medicine.

MedWatch Reporting Forms and Process

• Information is provided to the FDA using Form 3500 (health professionals), Form 3500A (pharmaceutical manufacturers, mandatory reporting), and Form 3500B (consumers).

What Occurs After MedWatch Submission

• Once submitted, the adverse event report is entered into a post-marketing surveillance database and reviewed case-by-case by a safety evaluator.
• Each case report is evaluated for: adequacy of information, temporal association, potential confounding factors, and de-challenge/re-challenge information (if available).
• Safety issues are investigated further within the agency and with the manufacturer.
• Actions taken may include labeling changes or educational initiatives.

MedWatch as a Post-Marketing Surveillance System

• MedWatch is a pharmacovigilance system.
• It has been a crucial source of safety information for regulating drug safety.