clinical data review best practices - e. herbel
TRANSCRIPT
![Page 1: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/1.jpg)
Survey of Best Practicesfor Clinical Data Review
Eric S. HerbelPresident
www.i-review.com
#CDLive13 1
![Page 2: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/2.jpg)
Data review for ongoing clinical trials
Over the past 10 years, the duration and complexity of clinical trials have steadily increased, Pharmaceutical R&D budgets are tighten and less resources on longer and more complex clinical trials have been observed. It becomes more critical to conduct clinical trials with more effective and innovative approaches.
Introduction
#CDLive13 2
![Page 3: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/3.jpg)
CRAs would review 100% of paper Case Report Forms
Data management and clinical personnel would review 100% of data listings.
Exhausting, error prone
Treats ‘all data as equal importance’
Data Review – Historical Perspective
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 3
![Page 4: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/4.jpg)
Current trend in many areas – Risk Based
Risk based approach to Systems …Risk Analysis …
Risk based monitoring
Risk based site selection for audits (FDA)
Risk Based …
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 4
![Page 5: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/5.jpg)
Current trend in many areas – Risk Based
Risk Based = Focus on highest risk issues
Don’t get ‘bogged down in the weeds’
Risk Based …
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 5
![Page 6: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/6.jpg)
Review clinical data – from an aggregate view – to the details.
Review summarized views of the data - for an overview of the data in your trial – lets you look into the items of interest based on the aggregate view of the data, rather than doing a patient by patient review of a detail line listing directly
Clinical Data Review
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 6
![Page 7: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/7.jpg)
Review summarized views of the data - for an overview of the data in your trial –
identify unexpected trends or values –especially important in safety data – that wouldn’t be recognized by detail patient data review.
Clinical Data Review
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 7
![Page 8: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/8.jpg)
Tabular Summaries
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 8
![Page 9: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/9.jpg)
Summary to Detail
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 9
![Page 10: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/10.jpg)
Demonstration of examplesAdverse EventsLabsVital Signs
*** Patient Level Drilldown very useful.
Summary to Detail
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 10
![Page 11: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/11.jpg)
A different type of ‘aggregate’ to detail pattern – is based on starting with a graphical aggregate view – such as either scatter plots, bar charts, box whiskers, etc– with graph patient profiles or detail listings displayed at the same time – to investigate ‘outliers’.
*** Patient Level Drilldown very useful.
Graphic Aggregate Review
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 11
![Page 12: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/12.jpg)
Graphic Aggregate -> Detail
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 12
![Page 13: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/13.jpg)
Graphic Aggregate -> Detail
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 13
![Page 14: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/14.jpg)
Demonstration of examplesScatter Plots (Labs, Vitals, etc.)Hy’s Law (DILI)Box Whiskers (distributions)Bar Charts (distributions/values)
*** Patient Level Drilldown very useful.
Graphic Aggregate to Detail
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 14
![Page 15: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/15.jpg)
Types of Review
1. Clinical Data Management-Quality Review
2. Medical Monitoring-Ongoing Safety Review
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 15
![Page 16: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/16.jpg)
Data validation – ensuring validity and consistency of data
Data checks to detectdata entry issues/errorscoding errors or inconsistencieslogical data inconsistencies
Data Quality Review
#CDLive13
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 201316
![Page 17: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/17.jpg)
Missing data identificationData reconciliationQuery handlingOutlier detectionPreparation for data analysis.
Data Quality Review
#CDLive13
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 201317
![Page 18: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/18.jpg)
Computer assisted data checking- check for impossible data using ranges (RDC)- check for required fields (RDC)- check for protocol violations (RDC & more advanced checks)- logical consistency checks
related date consistencieslogical relationship of answers
AE – outcome=med taken -> check if Conmed with corresponding indication
- review descriptive statistics for strange patterns
-> may lead to ‘queries’
Data Quality Review
#CDLive13
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 201318
![Page 19: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/19.jpg)
Computer assisted data checking- Highlighted Exceptions or Exception Listings (only exceptions)
Data Quality Review
#CDLive13
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 201319
![Page 20: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/20.jpg)
Consistency Checks- Consistency across study, across visits- check AEs, Conmeds, Dosage- Check dates – start/stop dates, overlapping?
- logical consistency checks across ‘CRF’ pagesAEs(action taken=med) -> Conmeds (indication?)
(date merge reports)
-> May lead to queries
Data Quality Review
#CDLive13
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 201320
![Page 21: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/21.jpg)
Consistency Checkslogical consistency checks across ‘CRF’ pages
Data Quality Review
#CDLive13
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 201321
![Page 22: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/22.jpg)
Coding – consistency/accuracy- Review original text vs. coded terms- Missing coded terms?- Check dates – start/stop dates, overlapping?
Coding Consistency
#CDLive13
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 201322
![Page 23: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/23.jpg)
Review protocol violations- Inclusion/Exclusion criteria- Data based protocol violations –
- disallowed meds?- objective checks of protocol entrance criteria (BP
levels, etc.)- Study drug dosing, termination- Switched group?- Expected/required page inventory
- review primary safety & efficacy endpoints
Protocol Violations
#CDLive13
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 201323
![Page 24: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/24.jpg)
Ongoing review of accumulating, blinded, aggregated study data to:
Ensure patient safetyEnsure study integrityImprove understanding of data
Patient safety – look at safety data in aggregate to spot trends of concern then inspect patients of interest.
Medical Monitoring <> Data Review
Medical Monitoring
#CDLive13
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 201324
![Page 25: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/25.jpg)
Medical Monitoring
Adverse EventsAggregate view(crosstab)
by highest freq.
Drill into AE cells-> Detail listings –Date Merged
(AE/Conmed)
Medical History
. . .
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 25
![Page 26: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/26.jpg)
Medical Monitoring
Lab Scatter PlotsBaseline/Endpoint, etc.
Looking for outliers,lab abnormalities
Click on outlier points-> Graph Patient Profiles
to see single patientview of related events
-> click conmed bar, etc.
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 26
![Page 27: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/27.jpg)
Medical Monitoring
Adverse EventsAE Risk Assessment.
Click on Risk Ratio point-> Detail listings –Date Merged
(AE/Conmed)
Medical History
. . .
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 27
![Page 28: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/28.jpg)
Medical Monitoring Protocol Adherence
Check ProtocolIncl/Excl Criteria
Important Criteria ValuesExample:Hypertensive trialwith one site enrollingmostly marginallyhypertensive patients.
Action: talk with site.
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 28
![Page 29: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/29.jpg)
Medical Monitoring
Lab Scatter PlotsBaseline/Endpoint, etc.
Looking for outliers,lab abnormalities
Click on outlier points-> Graph Patient Profiles
to see single patientview of related events
-> click conmed bar, etc.
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 29
![Page 30: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/30.jpg)
Medical MonitoringPatient Review Tracking – more later
I-Review’d checkbox-> I’ve reviewed patient
Subsequent data updates‘new/updated’ datahighlighted
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 30
![Page 31: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/31.jpg)
Risk Assessment
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 31
![Page 32: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/32.jpg)
Risk Assessments RR: HLGT Patient Subsets
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 32
![Page 33: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/33.jpg)
Risk Assessments RR Profiles: Patient Subsets
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 33
![Page 34: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/34.jpg)
Line Chart Summaries Laboratory Examples: Liver fn lab tests
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 34
![Page 35: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/35.jpg)
Chg from baseline Box Whiskers
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 35
![Page 36: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/36.jpg)
Chg from Baseline Box Whiskersselect outliers
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 36
![Page 37: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/37.jpg)
Chg from Baseline Box Whiskers
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 37
![Page 38: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/38.jpg)
%Chg from Baseline Bar ChartsHematology: Platelets lab test % Chg from Baseline
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 38
![Page 39: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/39.jpg)
Shifts from Baseline Laboratory Analysis
Baseline vs Max, Baseline vs Min for example
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 39
![Page 40: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/40.jpg)
Shifts from Baseline Laboratory Analysis
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 40
![Page 41: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/41.jpg)
Identify patients with abnormal lab results and shift from Baseline
Hemoglobin Shift from Baseline
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 41
![Page 42: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/42.jpg)
Identify patients with abnormal lab results and shift from Baseline
Hemoglobin Shift from Baseline
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 42
![Page 43: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/43.jpg)
Kaplan Meier Rate/Time to death analysis
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 43
![Page 44: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/44.jpg)
Mean Time to Disposition Events
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 44
![Page 45: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/45.jpg)
Special Assessments HepatotoxicityHy’s Law (DILI)
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 45
![Page 46: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/46.jpg)
Graphical Patient Profilesfrom Hy’s Law plot – patient drilldown
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 46
![Page 47: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/47.jpg)
Special Assessments Hepatotoxicity
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 47
![Page 48: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/48.jpg)
Hy’s Law example –explore why patients meet
the Hy’s Law criteriaUsing
Graphical Patient Profile
Special Assessments Hepatotoxicity
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 2013#CDLive13 48
![Page 49: Clinical Data Review Best Practices - E. Herbel](https://reader033.vdocuments.us/reader033/viewer/2022052620/557acf65d8b42a2c0f8b4f58/html5/thumbnails/49.jpg)
Preparation for Data Analysis
#CDLive13
• Check for Missing Data or Missed Coding, for example, AE MedDRA term mapping
Look for Reported (Verbatim) Adverse Events which don’t havecorresponding MedDRA terms (SOC, HLGT, HLT, PT, etc.)
If AE analysis is based on coded terms (SOC, etc.), and not all AEs were mapped -> analysis not including all AEs
• Verify Visit, Visitname, Epoch/Period/Phase are mapped properly
The 5th Annual Meeting: Patient Safety - A Sustained Focus from Scientific Ideas to Innovative Medicines
May 12-15, 201349