Sequential CausalImpact Analysis
Methodology: Sequential Causal Decomposition
A single pooled CausalImpact analysis confounds the effects of Jakavi (ruxolitinib) and the beta-blocker because both interventions fall within the post-period. This report runs two separate Bayesian Structural Time Series (BSTS) analyses to disentangle their individual contributions:
Pre-period: 2026-01-08 to 2026-03-15
Post-period: 2026-03-16 to 2026-04-07
Estimates what Jakavi alone does, before the beta-blocker is introduced.
Pre-period: 2026-03-16 to 2026-04-07
Post-period: 2026-04-08 to 2026-10-24
Uses the Jakavi-only window as the new baseline, then estimates what the beta-blocker adds on top.
Each run uses 5000 MCMC iterations with weekly seasonality. Posterior tail-area probability < 0.05 indicates statistical significance. Credible intervals are 95% highest posterior density.
Run A: Jakavi Effect (Isolated)
Jakavi started 2026-03-16. Pre-period: 2026-01-08 to 2026-03-15 (67 days). Post-period: 2026-03-16 to 2026-04-07 (23 days, before beta-blocker).
| Metric | Absolute Effect | Relative Effect | 95% CI | Tail-area Prob | Verdict |
|---|---|---|---|---|---|
| HRV Mean RMSSD | +0.67 ms | +6.6% | [-4.38, +5.72] | p=0.127 | Not significant |
| Lowest Heart Rate | -3.25 bpm | -4.2% | [-15.30, +8.81] | p=0.017 | Favorable |
| Average Heart Rate | -3.46 bpm | -4.1% | [-18.16, +11.23] | p=0.026 | Favorable |
| Sleep Efficiency | +1.38 % | +1.8% | [-5.54, +8.31] | p=0.055 | Not significant |
Run B: Marginal Beta-Blocker Effect
Beta-blocker started 2026-04-08. Pre-period (Jakavi-only baseline): 2026-03-16 to 2026-04-07 (23 days). Post-period: 2026-04-08 to 2026-10-24 (200 days).
| Metric | Absolute Effect | Relative Effect | 95% CI | Tail-area Prob | Verdict |
|---|---|---|---|---|---|
| HRV Mean RMSSD | +16.42 ms | +151.5% | [+11.10, +21.74] | p<0.001 | Favorable |
| Lowest Heart Rate | -13.17 bpm | -18.0% | [-43.42, +17.09] | p<0.001 | Favorable |
| Average Heart Rate | -12.70 bpm | -15.6% | [-44.62, +19.22] | p<0.001 | Favorable |
| Sleep Efficiency | +3.15 % | +3.9% | [-4.26, +10.57] | p<0.001 | Favorable |
Combined Timeline View
Full timeline with both intervention points and counterfactual predictions overlaid. Blue dashed = Jakavi counterfactual, purple dashed = BB counterfactual.
Clinical Interpretation
Summary of each drug's isolated contribution to observed biometric changes. This sequential design helps attribute changes to the correct intervention, though N-of-1 limitations still apply.
| Metric | Jakavi Contribution | Beta-Blocker Contribution |
|---|---|---|
| HRV Mean RMSSD | No significant effect detected. Jakavi increased hrv mean rmssd by 0.7 ms (+6.6%), but p=0.127 (not significant). | Beta-blocker significantly increased hrv mean rmssd by 16.4 ms (+151.5%), p<0.001 - favorable. |
| Lowest Heart Rate | Jakavi significantly decreased lowest heart rate by 3.2 bpm (-4.2%), p=0.017 - favorable. | Beta-blocker significantly decreased lowest heart rate by 13.2 bpm (-18.0%), p<0.001 - favorable. |
| Average Heart Rate | Jakavi significantly decreased average heart rate by 3.5 bpm (-4.1%), p=0.026 - favorable. | Beta-blocker significantly decreased average heart rate by 12.7 bpm (-15.6%), p<0.001 - favorable. |
| Sleep Efficiency | No significant effect detected. Jakavi increased sleep efficiency by 1.4 % (+1.8%), but p=0.055 (not significant). | Beta-blocker significantly increased sleep efficiency by 3.1 % (+3.9%), p<0.001 - favorable. |
Caution: Run B has a shorter pre-period (Jakavi-only window) which may reduce statistical power. Effects flagged as non-significant may become significant with more post-BB data accumulation. The HEV co-infection is a confounder that cannot be disentangled in this design.