--- title: "NNT/NNH Calculator & Log-rank to Hazard Ratio" output: rmarkdown::html_vignette vignette: > %\VignetteIndexEntry{NNT/NNH Calculator & Log-rank to Hazard Ratio} %\VignetteEngine{knitr::rmarkdown} %\VignetteEncoding{UTF-8} --- ```{r, include = FALSE} knitr::opts_chunk$set(collapse = TRUE, comment = "#>") ``` ## Overview Systematic reviews frequently encounter trials that report incomplete survival data -- a log-rank p-value but no Hazard Ratio, or probabilities without a directly computed NNT. ParCC bridges these gaps with two tools in the **HR Converter** module. ## Tutorial A: Extracting a Hazard Ratio from a Log-rank Test ### The Scenario -- Adjuvant Chemotherapy in Colon Cancer An older trial (published 2005) reports: - Log-rank chi-squared = **6.8** - Total events (deaths) across both arms = **142** - The treatment arm had better outcomes The paper does not report a Hazard Ratio, which you need for your meta-analysis. ### The Peto Approximation When only summary log-rank statistics are available, the Peto method estimates: $$\ln(HR) = \pm \frac{\sqrt{\chi^2}}{\sqrt{E/4}}$$ with a 95% confidence interval: $$\ln(HR) \pm \frac{1.96}{\sqrt{E/4}}$$ where $E$ is the total number of events. ### In ParCC 1. Navigate to **Convert > HR -> Probability & NNT > Log-rank -> HR** tab. 2. Select input type: **Chi-squared statistic**. 3. Enter chi-squared = **6.8**, Total events = **142**. 4. Select direction: **Treatment is better** (HR < 1). 5. Result: **HR = 0.68** (95% CI: 0.51 - 0.91). ### Alternative: From a p-value If the paper reports only "log-rank p = 0.009": 1. Select input type: **p-value**. 2. Enter p = **0.009**, Total events = **142**. 3. ParCC converts the p-value to a z-statistic via $z = \Phi^{-1}(1 - p/2)$, then applies the same Peto formula. ## Tutorial B: Computing NNT for a Formulary Decision ### The Scenario -- Hospital P&T Committee A Pharmacy & Therapeutics committee asks: "How many patients must we treat with Drug X to prevent one additional death?" The trial reports: - 12-month mortality: Control = **18%**, Intervention = **12%** ### The Formula $$NNT = \left\lceil \frac{1}{ARR} \right\rceil = \left\lceil \frac{1}{p_{control} - p_{intervention}} \right\rceil$$ ### In ParCC 1. Navigate to **Convert > HR -> Probability & NNT > NNT/NNH** tab. 2. Select input mode: **Two Probabilities**. 3. Enter Control = **0.18**, Intervention = **0.12**. 4. Result: ARR = **6.0%**, NNT = **17**. **Interpretation:** For every 17 patients treated with Drug X for 12 months, one additional death is prevented. ### Other Input Modes ParCC supports four ways to compute NNT: | Input Mode | You provide | ParCC calculates | |-----------|------------|-----------------| | Direct ARR | Absolute risk reduction | NNT = ceil(1/ARR) | | Two Probabilities | Control & intervention probabilities | ARR, then NNT | | RR + Baseline | Relative Risk + control probability | ARR = p0 x (1 - RR), then NNT | | OR + Baseline | Odds Ratio + control probability | Converts to probabilities via Zhang & Yu, then NNT | ### NNT vs NNH When the intervention *increases* risk (ARR < 0), the result is reported as **NNH** (Number Needed to Harm) with an orange warning. This happens when testing safety endpoints rather than efficacy. ## When to Use These Tools - **Log-rank -> HR:** Systematic reviews where older trials lack HR estimates; indirect treatment comparisons needing HR inputs from published statistics. - **NNT Calculator:** Communicating treatment effects to clinicians and formulary committees; sensitivity analyses varying NNT across plausible baseline risk ranges. ## References 1. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. *Trials*. 2007;8:16. 2. Parmar MKB, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. *Statistics in Medicine*. 1998;17(24):2815-2834. 3. Altman DG, Andersen PK. Calculating the number needed to treat for trials where the outcome is time to an event. *BMJ*. 1999;319(7223):1492-1495.