diff --git a/docs/source/models/concept_models/vivarium_alzheimers/concept_model.rst b/docs/source/models/concept_models/vivarium_alzheimers/concept_model.rst index ec6011d6cc..f902ebc97b 100755 --- a/docs/source/models/concept_models/vivarium_alzheimers/concept_model.rst +++ b/docs/source/models/concept_models/vivarium_alzheimers/concept_model.rst @@ -366,6 +366,9 @@ scenario, and input draw. - Treatment completion stratification for transitions to `Full treatment effect` state allows us to validate the 10% discontinuation rate. Note that the diagram states `Full treatment effect LONG` and `Full treatment effect SHORT` are both considered the same status (`Full treatment effect`), but are stratified by completion status. + * - Months on treatment + - + - Only needed for simulants who discontinue treatment as others are definitionally 0 or 9. * - Treatment status person-time - Status (`In treatment/ Waiting for treatment`, `Full treatment effect`, `Waning treatment effect`, `No treatment effect`). Also stratify by treatment completion (completed, discontinuated) from transition observer diff --git a/docs/source/models/intervention_models/alzheimers/hypothetical_treatment.rst b/docs/source/models/intervention_models/alzheimers/hypothetical_treatment.rst index 1c65de7e51..aefb568d1b 100644 --- a/docs/source/models/intervention_models/alzheimers/hypothetical_treatment.rst +++ b/docs/source/models/intervention_models/alzheimers/hypothetical_treatment.rst @@ -94,12 +94,12 @@ Vivarium Modeling Strategy in_treat [label="Receiving treatment", style=dashed, shape=box] no_treat [label="No treatment effect [permanent]"] - treat [label="Full treatment effect LONG [5 y]"] - wane [label="Waning treatment effect LONG (update each step) [9 y]"] - - treat_short [label = "Full treatment effect SHORT [6 mo]"] - wane_short [label = "Waning treatment effect SHORT (update each step) [2.5 y]"] + treat [label="Full treatment effect LONG [6 y]"] + wane [label="Waning treatment effect LONG (update each step) [11 y]"] + discon_time [label = "Months to discontinuation D_t", style=dashed, shape=box] + treat_short [label = "Full treatment effect SHORT [(Months on Treatment/9) * 6 y]"] + wane_short [label = "Waning treatment effect SHORT (update each step) [(Months on Treatment/9) * 11 y]"] el -> test [label = "tested"] el -> el [label = "not tested"] @@ -113,7 +113,9 @@ Vivarium Modeling Strategy wait -> in_treat [label = "begins treatment"] in_treat -> treat [label = "completes (90%)", style=dashed] - in_treat -> treat_short [label = "discontinues (10%)", style=dashed] + + in_treat -> discon_time [label = "discontinues (10%)", style=dashed] + discon_time -> treat_short treat_short -> wane_short wane_short -> no_treat @@ -140,6 +142,11 @@ on a time step, they should also immediately continue to the next state during t For example, a simulant in `BBBM test eligible` who is tested and moves to `BBBM test received` would then immediately move to one of that state's two sinks, and would even move directly to another state during the same transition/ time step on a positive test. +The "Months to discontinuation" state randomly assigns a number of months the simulant will be on treatment +before discontinuing. The number of months then determines the duration of time with full and waning treatment effect. +For example, if a simulant discontinues after 4 months, they would have (4/9) * 6 years of +full effect, or 2.67 which we round to the nearest 6 month interval, which is 2.5 years. + Below are tables with details on how to model these states and transitions, and necessary data values. The value of :math:`i_{MCI}` in the :ref:`cause model <2021_cause_alzheimers_presymptomatic_mci_transition_data_table>` is now updated to be equal to :math:`h_{adj} = h_{MCI} \cdot R_h`, where :math:`h_{adj}` is the intervention-adjusted hazard rate used for progression to MCI, @@ -162,7 +169,11 @@ is defined below. - Lower value means more likely to initiate testing. Independent from testing propensities. * - :math:`I` - Time- and location-specific treatment initiation rate - - Lilly: "The percent of patients with a positive BBBM test who initiate treatment will vary by location and over time – but will not vary by age or sex. In the US: 30% of eligible patients initiate (constant 2030-2100); Japan: 80% of eligible patients initiate (constant 2030-2100); all other countries: 40% of eligible patients initiate in 2030, increasing linearly to 70% by 2035, remaining constant at 70% until 2100."" + - The percent of patients with a positive BBBM test who initiate treatment will vary over time – but will not vary by age, sex, or location. We will use a piecewise linear ramp-up with knots at the following (year, level) values: `(2022.0, 0), (2027.0, 0), (2035.5, 30), (2100.0, 80), (2101.0, 80)`. + - + * - :math:`D_t` + - Months to discontinuation + - A full course of treatment is 9 months. We assume simulants discontinue evenly for each monthly injection. The months to discontinuation will be assigned a uniformly distributed whole number between 1 and 8 inclusive. - * - :math:`R_h` - Effect hazard ratio @@ -202,13 +213,16 @@ is defined below. * - Receiving treatment - Treatment period is instantaneous. See :ref:`alzheimers_intervention_treatment_assumptions` for info about treatment/discontinuation timing. - Zero duration. Random draw + * - Months to discontinuation + - Period is instantaneous. See above notes for selection of months to discontinuation. + - Zero duration. Random draw. * - Full treatment effect LONG - Treatment takes effect exactly 6 months after receiving a positive BBBM test (if :math:`\text{prop}_I < I`) - On transition to this state, :math:`R_h = R_d`. Set :math:`h_{adj} = R_h \cdot h_{MCI}`, slowing progression to MCI. Transition from this state after the fixed duration. * - Full treatment effect SHORT - - - Same effect size as in `Full treatment effect LONG` but with a shorter fixed duration + - Same effect size as in `Full treatment effect LONG` but with a shorter fixed duration. The duration is dependent on the time of discontinuation, as outlined above. * - Waning treatment effect LONG - - On every time step where the simulant ends the time step in this @@ -221,7 +235,7 @@ is defined below. this state after the fixed duration. * - Waning treatment effect SHORT - - - Same effect size as in `Waning treatment effect LONG` but with a shorter fixed duration + - Same effect size as in `Waning treatment effect LONG` but with a shorter fixed duration. The duration is dependent on the time of discontinuation, as outlined above. * - No treatment effect - - :math:`R_h` should equal 1 on the first time step the simulant spends in this state.