In-silico approaches to assessing multiple high-level drug-drug and drug-disease adverse drug effects

Figures & data

Table 1. A single 2$\times$2 contingency table for a drug(i)-AE(j) pair in SRS for the number of reports given by counts and the associated probabilities.

Counts	AE (j)	All other AEs	Total
Drug (i)	$n_{\mathit{ij}}=\mathit{a}$	$n_{\mathit{i}.}-n_{\mathit{ij}}=\mathrm{b}$	$n_{\mathit{i}.}=\mathrm{a}+\mathrm{b}$
All other Drugs	$n_{.\mathit{j}}-n_{\mathit{ij}}=\mathrm{c}$	$n_{..}-n_{.\mathit{j}}-n_{\mathit{i}.}+n_{\mathit{ij}}$ = d	$n_{..}-n_{\mathit{i}.}=\mathrm{c}+\mathrm{d}$
Total	$n_{.\mathit{j}}=\mathrm{a}+\mathrm{c}$	$n_{..}-n_{.\mathit{j}}=\mathrm{b}+\mathrm{c}$	$n_{..}=\mathrm{a}+\mathrm{b}+\mathrm{c}+\mathrm{d}$
Probabilities	AE (j)	All other AEs	Total
Drug (i)	$p_{\mathit{ij}}$	$p_{\mathit{i}.}-p_{\mathit{ij}}$	$p_{\mathit{i}.}$
All other Drugs	$p_{.\mathit{j}}-p_{\mathit{ij}}$	$1-p_{.\mathit{j}}-p_{\mathit{i}.}+p_{\mathit{ij}}$	$1-p_{\mathit{i}.}$
Total	$p_{.\mathit{j}}$	$1-p_{.\mathit{j}}$	$1$

Table 2. Probabilistic Interpretations and estimators of association for the 2$\times$2 contingency table in SRS analysis.

Measure	Probabilistic Interpretation	Estimator
$\mathit{R}{\mathit{R}}_{\mathit{ij}}$	$\frac{\mathrm{Pr}\left(\mathit{AE}|\mathit{Drug}\right)}{\mathrm{Pr}\left(\mathit{AE}\right)}$	$\frac{{\mathit{p}}_{\mathit{ij}}}{p_{\mathit{i}.}\times p_{.\mathit{j}}}\approx \frac{\mathit{a}\left(\mathit{a}+\mathit{b}+\mathit{c}+\mathit{d}\right)}{\left(\mathit{a}+\mathit{c}\right)\left(\mathit{a}+\mathit{b}\right)}$
$\mathit{RO}{\mathit{R}}_{\mathit{ij}}$	$\frac{\mathrm{Pr}\left(\mathit{AE}|\mathit{Drug}\right)}{\mathrm{Pr}\left(\mathit{AE}|\sim \mathit{Drug}\right)}$	$\frac{{\mathit{p}}_{\mathit{ij}}\left(1-p_{.\mathit{j}}-p_{\mathit{i}.}+p_{\mathit{ij}}\right)}{\left(p_{\mathit{i}.}-p_{\mathit{ij}}\right)\left(p_{.\mathit{j}}-p_{\mathit{ij}}\right)}\approx \frac{\mathit{a}/c}{\mathit{b}/d}$
$\mathit{PR}{\mathit{R}}_{\mathit{ij}}$	$\frac{\text{Pr}\left(\mathit{AE}\text{|}\mathit{Drug}\right)/\text{Pr}\left(~\mathit{AE}\text{|}\mathit{Drug}\right)}{\text{Pr}\left(\mathit{AE}\text{|}~\mathit{Drug}\right)/\text{Pr}\left(~\mathit{AE}\text{|}~\mathit{Drug}\right)}$	$\frac{{\mathit{p}}_{\mathit{ij}}/p_{.\mathit{j}}}{\left(p_{\mathit{i}.}-p_{\mathit{ij}}\right)/\left(1-p_{.\mathit{j}}\right)}\approx \frac{\mathit{a}/\left(\mathit{a}+\mathit{b}\right)}{\mathit{c}/\left(\mathit{c}+\mathit{d}\right)}$
$\mathit{I}{\mathit{C}}_{\mathit{ij}}$	${log}_2\frac{\mathrm{Pr}\left(\mathit{AE}|\mathit{Drug}\right)}{\mathrm{Pr}\left(\mathit{AE}\right)}$	${log}_2\left(\frac{{\mathit{p}}_{\mathit{ij}}}{p_{\mathit{i}.}\times p_{.\mathit{j}}}\right)\approx {log}_2\left(\frac{\mathit{a}\left(\mathit{a}+\mathit{b}+\mathit{c}+\mathit{d}\right)}{\left(\mathit{a}+\mathit{c}\right)\left(\mathit{a}+\mathit{b}\right)}\right)$

Figure 1. Flowchart outlining a standard disproportionality analysis for data obtained from SRS.

Figure 2. Global trends in PhV publications from 2003 to 2023. The purple bars indicate the number of publications in each given year, highlighted by the y-axis on the left-hand side. The red line corresponding to the y-axis on the right-hand side represent the cumulative number of publications from 2003 to 2023.

Figure 3. The network structure (Top) and density plots (Bottom) of bibliometric analysis for the abstracts of PhV-related publications.

The acronyms used in each panel are as follows: AFF: Atypical Femoral Fracture, ARM: Association Rule Mining, aROR: Adjusted Reporting Odds Ratio, CKD: Chronic Kidney Disease, CVST: Cerebral Venous Sinus Thrombosis, GBS: Guillain-Barré Syndrome, IBD: Inflammatory Bowel Disease, ITP: Immune Thrombocytopenia, MRONJ: Medication-Related Osteonecrosis of The Jaw, NSCLC: Non-Small Cell Lung Cancer, PML: Personal Medication List, SDR: Signal Of Disproportionate Reporting, SGLT2: Sodium- Glucose Cotransporter-2, SRSs: Spontaneous Reporting Systems, TdP: Torsades Des Pointes, TKIs: Tyrosine Kinase Inhibitors, TNF-Is: Tumor Necrosis Factor-Α Inhibitors, VTE: Venous Thromboembolism.

Figure 4. Framework for assessing potential risks associated with multidrug-related system organ class toxicity in pharmacovigilance analytics.

Data availability statement

For original data, please contact the corresponding author, Majid Jaberi-Douraki, [email protected].