Improved Apriori Method for Safety Signal Detection Using Post-Marketing Clinical Data
Abstract
:1. Introduction
1.1. Safety Data Analysis
- High dimensionality: The number of AEs can be large (hundreds or even thousands), especially during the post-approval marketing phase when the medicine becomes available for broad populations. However, only a few of these AEs are significant for new discoveries about the product’s clinical safety.
- Sparsity: Most types of AEs are rare, especially in the stage of post-market surveillance, due to factors such as selective participant profiles in clinical trials, rare events in large populations, long-term effects and drug interactions, and more.
- Weak signal: Certain AEs may exhibit a low signal strength related to the drug or vaccine under investigation, which could potentially impact the efficacy of the methodologies employed to detect drug–AE associations.
- Complex correlation: AEs may demonstrate complex correlation structure among themselves, either positive or negative, which poses significant challenges in identifying AE signals associated with a drug or vaccine.
1.2. Apriori-Based Methods for Safety Signal Detection
2. Method
2.1. Classical Apriori Method
2.2. Improved Apriori Method
2.3. Numerical Studies
2.3.1. Simulation Studies
2.3.2. VAERS Data
3. Results
3.1. Simulation Study
3.1.1. Setting 1: One Drug and Three AEs
3.1.2. Setting 2: Three Drugs and Five AEs
3.1.3. Setting 3: Five Drugs and Ten AEs
3.2. VAERS Data
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Suspected AE | All Other AEs | Total | |
---|---|---|---|
Suspected drug | a | b | a + b |
All other drugs | c | d | c + d |
Total | a + c | b + d | a + b + c + d |
VAERS ID | VAERS ID Code | Vaccine Type | Vaccine Type Code | Symptoms | Symptoms Code |
---|---|---|---|---|---|
0376710-1 | 0376710-1 | DIPHTHERIA AND TETANUS TOXOIDS AND ACELLULAR PERTUSSIS VACCINE + INACTIVATED POLIOVIRUS VACCINE + HAEMOPHILUS B CONJUGATE VACCINE | DTAPIPVHIB | DEATH | 10011906 |
0376710-1 | 0376710-1 | DIPHTHERIA AND TETANUS TOXOIDS AND ACELLULAR PERTUSSIS VACCINE + INACTIVATED POLIOVIRUS VACCINE + HAEMOPHILUS B CONJUGATE VACCINE | DTAPIPVHIB | UNRESPONSIVE TO STIMULI | 10045555 |
0376710-1 | 0376710-1 | INFLUENZA VIRUS VACCINE, TRIVALENT (INJECTED) | FLU3(SEASONAL) | DEATH | 10011906 |
0376710-1 | 0376710-1 | INFLUENZA VIRUS VACCINE, TRIVALENT (INJECTED) | FLU3(SEASONAL) | UNRESPONSIVE TO STIMULI | 10045555 |
0376710-1 | 0376710-1 | PNEUMOCOCCAL, 7-VALENT VACCINE (PREVNAR) | PNC | DEATH | 10011906 |
0376710-1 | 0376710-1 | PNEUMOCOCCAL, 7-VALENT VACCINE (PREVNAR) | PNC | UNRESPONSIVE TO STIMULI | 10045555 |
0376969-1 | 0376969-1 | INFLUENZA (H1N1) MONOVALENT (INJECTED) | FLU(H1N1) | COAGULOPATHY | 10009802 |
0376969-1 | 0376969-1 | INFLUENZA (H1N1) MONOVALENT (INJECTED) | FLU(H1N1) | DEATH | 10011906 |
0376969-1 | 0376969-1 | INFLUENZA (H1N1) MONOVALENT (INJECTED) | FLU(H1N1) | DRUG INTERACTION | 10013710 |
Associated Pairs | Non-Associated Pairs | Total | |
---|---|---|---|
Selected | a (TP) | b (FP) | a + b |
Not selected | c (FN) | d (TN) | c + d |
Total | a + c | b + d | a + b + c + d |
Parameter | Boundary Values | Threshold | Selected Pairs |
---|---|---|---|
Confidence | (0,1) | 0.4 | 33 |
0.5 | 30 | ||
0.6 | 28 | ||
0.7 | 26 | ||
PRR | (0,∞) | 1 | 341 |
1.2 | 308 | ||
1.5 | 272 | ||
2 | 214 | ||
RR | (0,∞) | 1 | 341 |
1.2 | 300 | ||
1.5 | 246 | ||
2 | 153 | ||
ROR | (0,∞) | 1 | 341 |
1.2 | 321 | ||
1.5 | 282 | ||
2 | 232 |
Vaccine Code | Vaccine Name | AE/Symptom Name | Support | ROR (0,∞) | PRR (0,∞) | RR (0,∞) | Confidence (0,1) |
---|---|---|---|---|---|---|---|
DTAPIPVHIB | DIPHTHERIA AND TETANUS TOXOIDS AND ACELLULAR PERTUSSIS VACCINE + INACTIVATED POLIOVIRUS VACCINE + HAEMOPHILUS B CONJUGATE VACCINE | UNRESPONSIVE TO STIMULI | 25 | 2.059 | 1.867 | 1.609 | 0.181 |
FLU3 (SEASONAL) | INFLUENZA VIRUS VACCINE, TRIVALENT (INJECTED) | NAUSEA | 8 | 2.061 | 2.002 | 1.681 | 0.056 |
DTAPHEPBIP | DIPHTHERIA AND TETANUS TOXOIDS AND ACELLULAR PERTUSSIS VACCINE + HEPATITIS B + INACTIVATED POLIOVIRUS VACCINE | RESPIRATORY ARREST | 15 | 2.063 | 1.939 | 1.668 | 0.116 |
RV5 | ROTAVIRUS VACCINE, LIVE, ORAL, PENTAVALENT | RESUSCITATION | 35 | 2.074 | 1.853 | 1.551 | 0.206 |
HEPA | HEPATITIS A | INTENSIVE CARE | 4 | 2.074 | 1.972 | 1.870 | 0.095 |
HIBV | HAEMOPHILUS B CONJUGATE VACCINE | PALLOR | 3 | 2.077 | 2.055 | 1.703 | 0.020 |
HIBV | HAEMOPHILUS B CONJUGATE VACCINE | DEHYDRATION | 3 | 2.077 | 2.055 | 1.703 | 0.020 |
HIBV | HAEMOPHILUS B CONJUGATE VACCINE | RHINORRHOEA | 3 | 2.077 | 2.055 | 1.703 | 0.020 |
PPV | PNEUMOCOCCAL VACCINE, POLYVALENT | INTENSIVE CARE | 3 | 2.082 | 1.977 | 1.900 | 0.097 |
HIBV | HAEMOPHILUS B CONJUGATE VACCINE | APNOEA | 4 | 2.084 | 2.055 | 1.703 | 0.027 |
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Sarkar, R.; Sun, J. Improved Apriori Method for Safety Signal Detection Using Post-Marketing Clinical Data. Mathematics 2024, 12, 2705. https://doi.org/10.3390/math12172705
Sarkar R, Sun J. Improved Apriori Method for Safety Signal Detection Using Post-Marketing Clinical Data. Mathematics. 2024; 12(17):2705. https://doi.org/10.3390/math12172705
Chicago/Turabian StyleSarkar, Reetika, and Jianping Sun. 2024. "Improved Apriori Method for Safety Signal Detection Using Post-Marketing Clinical Data" Mathematics 12, no. 17: 2705. https://doi.org/10.3390/math12172705