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Medical review in case processing

Medical review of an individual case is an important step in case processing. Generally performed after data entry and quality control (QC) checks, I would consider it a super QC

The key aspects of the case that are reviewed during the Medical Assessment step are as follows:

  • Seriousness
  • Expectedness
  • Causality
  • Case Medical Information
  • Reportability Classification

Which cases undergo Medical Review?

  • Findings from clinical studies, epidemiological studies or pooled data
  • Death
  • SUSARs
  • Events of Medical Interest/ Adverse Events of Special Interest
  • Serious Spontaneous cases
  • Solicited post marketing cases

A Medical Review should cover the following:

  • Confirm appropriateness of the AE terms selected. Is the correct term selected based on the available information? In some cases, one might have to match the verbatim with clinical picture.
  • Confirmation of the seriousness classification of the AE terms. A change of seriousness would force an upgrade or downgrade of the case in turn changing reportability timelines. Something that was to be reported in 2 weeks’ time might suddenly become urgent. If this is missed at this time one might realise it only at the time of filing a Periodic Safety Update Report (PSUR), when all cases are listed and reviewed. Such extreme delay could invite strong penalties if the adverse event is critical to the evaluation of product risk.
  • Agreement with the listedness/expectedness classification of AE terms. Sponsors provide many conventions to be followed for listedness determination in different situations. Here again something unexpected and serious would make the case a Suspected Unexpected Serious Adverse Event (SUSAR), to be assigned for expedited reporting and delays could have results as above
  • Consideration of ‘upgrade’ or ‘downgrade’ to the case’s regulatory reportability classification.
  • Agreement with outcome classification. Often missed at data entry because the information is couched somewhere in the narrative about patient’s condition not improving, or investigation parameters showing deterioration over time
  • Agreement with the coding of AEs, concomitant conditions, and medical history. Is the coding (MedDRA and drug names) correct?  For MedDRA codes some level of medical knowledge is required for accurate coding as well as familiarity with MedDRA conventions, hierarchy etc.
  • Review of the narrative to ensure that it makes clinical sense and includes all important elements. does the narrative convey the essence of the case correctly without need for the reader to look at the source documents?

    As Per guidelines for Good Pharmacovigilance practices Module VI, a patient safety narrative should describe:
    • the event and its evolution
    • intensity and outcome of the event,
    • its occurrence in relation to timing of study drug administration,
    • relevant laboratory investigations,
    • how was the event managed; medically, surgically any other means
    • action taken on the study drug with reference to dose, timing
    • post mortem findings in case the event is fatal
    • Investigator’s opinion on causality
  • Authoring the company clinical comment, including determination of the company causality assessment, when appropriate. The company causality may or may not agree with that of the reporter but a proper justification needs to be provided. This includes expectedness, temporality, confounding factors like comorbidities, relevant investigations etc.
  • Identification of any specific additional information needed for medical assessment purposes other than routine follow-up requests required for case completion. Pursuit of follow-up on single case reports should be tailored according to the importance of the case in terms of attempts made and methods used (CIOMS, 2001).
  • Generation of queries: In fact, drafting a query is an acquired skill. A general query asking for all investigations, comorbidities etc confuses the reporter/investigator resulting in a delayed and inappropriate response that requires repeat queries. Sometimes follow up queries are being answered 8-9 months after the death of the patient. This results in unnecessary waste of resources since at every follow up the case has to undergo the whole case management cycle; case log, triage, data entry, quality check, medical review and closure. A specific, well-crafted query will generate the precise response helping to close the case early.
  • Identification of potential safety signals. A medical reviewer is well placed to identify safety signals even before subjecting the data to statistical review. Since s/he is handling numerous cases every day, day after day, s/he is best placed to identify a recurring pattern and develop a hypothesis for further testing

Changes due to automation

Today, every step is being evaluated to see if it can be automated, so as to improve accuracy, reduce time and cost. Automation in pharmacovigilance case processing eliminates steps of case booking, data entry, triage and quality control. Triage is one area where machine learning can happen. The culmination is that all such cases land at the medical reviewer’s table.

This indicates that the medical reviewer’s role is going to be all the more important in future. This is one area that is not easy to substituted by artificial intelligence.


  1. Cobert B Jan 8 2014 https://www.c3isolutions.com/blog/medical-review-individual-case-safety-reports/ Downloaded 20 March 2020
  2. EU Guideline on good pharmacovigilance practices (GVP) Module VI Downloaded May 2020
  3. Patient safety narratives in Clinical studies. White paper Quanticate
Dr. Vishwas Sovani (May 2020)


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Medical review, pharmacovigilance, automation, company comment, listedness, narrative, coding, MedDRA, outcome classification, upgrade , downgrade