Dataset Information

Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale.

ABSTRACT:

Background

In both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events.

Methods

The effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery.

Results

The multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05) whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61). The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged < = 60 and in patients >70.

Conclusions

The present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification.

SUBMITTER: Girerd N

PROVIDER: S-EPMC4821587 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale.

Girerd Nicolas N Rabilloud Muriel M Pibarot Philippe P Mathieu Patrick P Roy Pascal P

PloS one 20160405 4

<h4>Background</h4>In both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinica ...[more]

PMID: 27045168

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Project description:Additive and multiplicative regression models of habituation were compared regarding the fit to looking times from a habituation experiment with infants aged between 3 and 11 months. In contrast to earlier studies, the current study considered multiple probability distributions, namely Weibull, gamma, lognormal and normal distribution. In the habituation experiment the type of contrast between the habituation and the test trial was varied (luminance, color or orientation contrast), crossed with the number of habituation trials (1, 3, 5, or 7 habituation trials) and crossed with three age cohorts (4, 7, 10 months). The initial mean LT to dark stimuli (around 3.7 s) was considerably shorter than the mean LT to green and gray stimuli (around 5 s). Infants showed the strongest dishabituation to changes from dark to bright (luminance contrast) and weak-to-no dishabituation to a 90-degrees rotation of the gray stimuli (orientation contrast). The dishabituation was stronger after five and seven habituation trials, but the result was not statistically robust. The gamma distribution showed the best fit in terms of log-likelihood and mean absolute error and the best predictive performance. Furthermore, the gamma distribution showed small correlations between parameters relative to other models. The normal additive model showed an inferior fit and medium correlations between the parameters. In particular, the positive correlation between the initial looking time (LT) and the habituation rate was likely responsible for a different interpretation relative to the multiplicative models of the main effect of age on the habituation rate. Otherwise, the additive and multiplicative models provided similar statistical conclusions. The performance of the model versions without pooling and with partial pooling across participants (also called random-effects, multi-level or hierarchical models) were compared. The latter type of models showed worse data fit but more precise predictions and reduced correlations between the parameters. The performance of model variants with auto-regressive time structures were explored but showed considerably worse fit. The performance of quadratic models that allowed non-monotonic changes in LTs were investigated as well. However, when fitted with LT data, these models did not produce non-monotonic change in LTs. The study underscores the utility of partial-pooling models in terms of providing more accurate predictions. Further, it agrees with previous research in that a multiplicative LT model is preferable. Nevertheless, the current results suggest that the impact of the choice of an additive model on the statistical inference is less dramatic then previously assumed.

Project description:BackgroundPredictive microbiology develops mathematical models that can predict the growth rate of a microorganism population under a set of environmental conditions. Many primary growth models have been proposed. However, when primary models are applied to bacterial growth curves, the biological variability is reduced to a single curve defined by some kinetic parameters (lag time and growth rate), and sometimes the models give poor fits in some regions of the curve. The development of a prediction band (from a set of bacterial growth curves) using non-parametric and bootstrap methods permits to overcome that problem and include the biological variability of the microorganism into the modelling process.ResultsAbsorbance data from Listeria monocytogenes cultured at 22, 26, 38, and 42 degrees C were selected under different environmental conditions of pH (4.5, 5.5, 6.5, and 7.4) and percentage of NaCl (2.5, 3.5, 4.5, and 5.5). Transformation of absorbance data to viable count data was carried out. A random effect multiplicative heteroscedastic model was considered to explain the dynamics of bacterial growth. The concept of a prediction band for microbial growth is proposed. The bootstrap method was used to obtain resamples from this model. An iterative procedure is proposed to overcome the computer intensive task of calculating simultaneous prediction intervals, along time, for bacterial growth. The bands were narrower below the inflection point (0-8 h at 22 degrees C, and 0-5.5 h at 42 degrees C), and wider to the right of it (from 9 h onwards at 22 degrees C, and from 7 h onwards at 42 degrees C). A wider band was observed at 42 degrees C than at 22 degrees C when the curves reach their upper asymptote. Similar bands have been obtained for 26 and 38 degrees C.ConclusionsThe combination of nonparametric models and bootstrap techniques results in a good procedure to obtain reliable prediction bands in this context. Moreover, the new iterative algorithm proposed in this paper allows one to achieve exactly the prefixed coverage probability for the prediction band. The microbial growth bands reflect the influence of the different environmental conditions on the microorganism behaviour, helping in the interpretation of the biological meaning of the growth curves obtained experimentally.

Dataset Information

Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale.

Background

Methods

Results

Conclusions

Publications

Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale.

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