This document discusses trends in clinical trial data analysis and reporting. It covers medical queries, including standard medical queries (SMQs) defined by MedDRA to group adverse events, custom medical queries (CMQs) defined by drug companies, and FDA medical queries. It discusses MedDRA's classification structure and provides an example of a device high level group term. The document also discusses algorithmic FDA medical queries (aFMQs) that use additional data beyond adverse event terms. It covers standard analyses for liver injury including Hy's Law plots and tables based on laboratory findings. It concludes with an overview of the software JMP Clinical which facilitates many of these standard clinical trial analyses and report generations.

1. Clinical Trials Analysis Trends &
JMP Clinical
Sam Gardner
Senior Product Manager
Health and Life Sciences
JMP Statistical Discovery
Discovery Summit Korea 2023

2. Overview
JMP Clinical

3. Trends in Clinical Trial Data Analysis and Reporting
§ Medical Queries
§ Safety Tables and Figures Guidelines
§ Drug-Induced Liver Injury

4. Medical Queries
§ Medical Dictionary for Regulatory Activities
(MedDRA) (meddra.org) define standard terms for
classifying adverse events (AEs) and are used in most
clinical trials.
§ Standard Medical Queries (SMQs) – Defined by
MedDRA, used as a first step in grouping standard
AEs that are indicative of a medical or safety issue

5. MeDDRA Terms
§ Classification Structure
§ 27 System Organ Classes (SOC)
§ 337 High Level Group Terms (HGLT)
§ 1737 High Level Terms (HLT)
§ 25,916 Preferred Terms (PT)
§ 86,714 Low Level Terms (LLT)

6. Example
Device High Level
Group Term had
Issues has 8 High
Level Terms
Low Level Terms:
Device On Fire!
System or Organ Class = “Product Issues”

7. Medical Queries
§ Custom Medical Queries (CMQs) – allows drug company
sponsors to define their own groupings of AE terms or for
specific Adverse Events of Interest
§ FDA Medical Queries: US Food and Drug Administration (FDA)
custom medical queries (>100), for groupings of safety terms
of interest to the agency
§ Draft guideline shared Sept 6, 2022
https://www.regulations.gov/docket/FDA-2022-N-1961

8. Standard Medical Query Risk
§ Count the number of subjects that have had Evidence
of hepatic disorders (Liver Injury) in each treatment
arm and compare the rates in each group
SMQs have both Broad and Narrow term groupings.
Treatment
group

9. FDA Medical Queries (FMQ) Example
The FMQ for Anxiety
captures many Preferred
Terms that are related to
Anxiety.
Just using the “Anxiety”
Preferred Term, the rate
of occurrence appears to
below the clinically
relevant rate, but the FMQ
shows a higher rate that is
more clinically relevant.
Source: https://cacmap.fda.gov/media/164639/download

10. Algorithmic FDA Medical Queries (aFMQ)
§ aFMQ use more than just the standard AE preferred
terms
§ Uses additional data from laboratory findings, vital
signs, concomitant medications, and disposition
§ Much more complicated search to find subjects that
meet the criteria

11. aFMQ for Hyperglycemia
The Hyperglycemia FMQ has an algorithmic component that includes all patients who meet any of the following criteria:
1. Any PT from Hyperglycemia FMQ Narrow
2. Fasting Plasma Glucose ≥126 mg/dL
3. ≥2 Plasma Glucoses >180 mg/dL
4. Any New Diabetes Concomitant Medication:
o The medication must have been started following enrollment
o CMINDC File
§ INCLUDE diab, mellitus, hyperglyc, glucose, dibet, dieb
§ EXCLUDE prophyla, prevent, insipidus, hyperglycerid, low blood glucose, low glucose, low blood sugar, low sugar, low
afternoon blood glucose, low morning blood glucose
o CMCLAS File
§ INCLUDE gliptin, glutide, diabet, glitaz, glucose lowering, glucosidas, dipeptidyl, sulfonyl, DPP, guanide, GLP, glucagon-like,
metform, gliflozin, insulin, sodium-glucose, SGLT, thiazolid
§ EXCLUDE sex hormone
§ 5. Post Baseline HbA1c ≥6.5%
§ 6. HbA1c Increase ≥0.3% with Post Baseline HbA1c ≥5.7%
§ 7. Change from Baseline Fasting Plasma Glucose ≥20 mg/dL with Post Baseline Fasting Plasma Glucose>100 mg/dL

12. aFMQ Risk Report
The rates of Hyperglycemia are clinically relevant
and the difference between the treatment and
placebo group is nearly statistically significant.

13. Drug-Induced Liver Injury (DILI)
§ Finding subjects with evidence of liver injury is an important
issue in almost every clinical trial. Liver injury is one of the
most common serious adverse events related to drugs.
§ Many types of data searches can be used
§ Medical Queries (SMQ, FMQ, aFMQ)
§ Plots of laboratory results and change in laboratory results (Hy’s Law)
§ Discontinuations
§ Missing Lab Records

14. FDA Guidelines
Newer Guidance with
Recommendations for Queries,
Reporting, and Visualization of
Safety Results
Long-standing Guidance on DILI
(2009)
New Draft Guidance on Safety Analysis
(2022)

15. Screening for Liver Injury – Hy’s Law
Examine ratio of Liver Lab test
results with the Upper Limit of
Normal (ULN) à Hy’s Law
Subjects in upper right corner of
plot may have liver injury
Scatterplot of Bilirubin/ULN vs Alanine
Aminotransferase/ULN

16. Change in Liver Enzymes During Study
Looking for Shifts in Laboratory
Results Over Time
Subjects with unusual shift high
during the trial
Peak ALT vs Baseline ALT

17. DILI Tables based on Laboratory Findings

18. Missing Lab Results
Missing Lab Results
May Indicate Insufficient
Data or Bias in
Assessing Liver Injury
Risk

19. JMP® Clinical Has All of These
§ With a few clicks of a mouse, you can create
§ Interactive Standard and Custom Medical Queries
§ Interactive FDA Medical Query
§ Interactive Algorithmic FDA Medical Query
§ Hy’s Law
§ Interactive DILI Analysis*
* coming soon in version 18

20. What is JMP Clinical?
§ JMP Clinical is an application built on JMP Pro
§ Focused and specialized product for clinical trial data analysis that utilizes
the Clinical Data Interchange Standards Consortium (CDISC) data standards
and creates standardized analysis reports.
§ Utilized across the pharmaceutical industry and regulatory agencies
§ Applications:
§ Safety Analysis
§ Medical Monitoring
§ Medical Writing
§ Study Monitoring & Clinical Data Review

21. JMP Clinical In Action
Demo

22. Find Out More about JMP® Clinical
§ www.jmp.com/clinical
§ Contact your local sales team
§ Reach out to me -- Sam.Gardner@JMP.com