NextDose: A web-based Bayesian dose forecasting tool

Last updated 29 July 2021

Creating a User Account

NextDose requires you use an email address as a user name (Figure 1). You will be asked to create a password the first time you try to login.

Figure 1

NextDose system administrators do not by default have access to user or group accounts. Users or group administrators may invite a NextDose administrator to be a co-administrator to help solve problems.

Creating a Group Account

If you wish to have others have secure access to the same patient data and results then you can apply to be the administrator of a group (see link in light blue box in Figure 1). Administrators can modify group details and add members to the group. All members of the group can see and change data and execute runs using patient data associated with that group. The data cannot be seen by anyone outside the group.

Getting Started

Patient details such a patient identifier, sex and genotype that do not change with time may be entered here. Age at entry or date of birth are entered as well so that patient age can be calculated. If age is less than 1 year then you will be asked to enter gestation age (enter 40 weeks if you don’t know).

After selecting a medicine you can then enter basic observations to calculate an initial dosing scheme then enter dose and response observations to calculate a follow up dosing scheme. Basic observations include things like weight, height, serum creatinine that may change with time. They are not response observations like drug concentration or INR. Basic observations are also known as covariates and response observations are also known as dependent variables.

There are two fundamental steps (FirstDose, NextDose) when using NextDose. A quick start overview of the process is shown here:

Figure 2

1. Add a patient by clicking on the + at the side of the Find Patient box.

2. Enter patient details.

3. Add a medicine by clicking on the + at the side of the Add a new medicine box.

4. Add weight as an observation. Weight is a basic observation that is always required.

5. The FirstDose step -- predict an initial dosing scheme by clicking on Results (top menu) and Calculate (blue button) (use the default choices until you get more comfortable).

a. You will see dosing recommendations (loading dose and maintenance dose) and a graph of predicted values such as concentrations.

b. The dosing recommendations and graph are based on the patient details and basic observations you entered.

6. Return to the Doses and Observations page.

7. Enter one or more doses.

8. Enter one or more response observations such as drug concentration or INR.

9. The NextDose step -- predict a follow up dosing scheme by clicking on Results (top menu) and Calculate (blue button) (use the default choices until you get more comfortable).

a. You will see dosing recommendations (loading dose and maintenance dose) and a graph of predicted values such as concentrations.

b. The dosing recommendations and graph are based on the doses and the response observations you entered.

10. Each time you change the doses, basic or response observations a new instance of the patient data is created. These can be accessed through the menu of dates and times on the left hand side of the NextDose window.

Getting Started with Pictures

There are two fundamental steps (FirstDose, NextDose) when using NextDose. An overview of the process is shown here with screen images:

1. Add a patient by clicking on the + at the side of the Find Patient box.

2. Enter patient details. Do not select Demo patient unless you wish to share with all other NextDose users. When finished click Save Changes.

Figure 3

3. Add a medicine by clicking on the + at the side of the Add a new medicine box.

Figure 4

4. Add weight as an observation. Weight is a basic observation that is always required. If height is not entered it will be imputed to help calculate fat free mass. Try to enter height if you can to improve size predictions. Always remember to Save changes after entering an Observation or Dose.

Figure 5

5. The Results step -- predict a dosing scheme by clicking on the Results menu item (top menu). You are offered a set of Dose Prediction options. Use the default values of the options until you get more comfortable with using NextDose.

a. The Dose Prediction options are:

i. Model: Choose from a drop down list of alternative models to select a model to calculate pharmacokinetic parameters and dose predictions.

ii. Target: The target is specified by a numerical value and a drop down list of target types. The units of the target value and the type of target are specified by the target type. Typical types are

1. Average steady state value (Cssavg). If you change the Dose Interval there is no need to change the target value.

2. AUC specified over the Dose Interval (AUCssDI). Be careful when using the AUCssDI target type. The Dose Interval (DI) option will be used as the interval to calculate the target AUC. If you half the Dose interval from 24 h to 12 h then you should half the target value e.g. from 400 to 200 mg/L*h to get the same average steady state value with different dosing intervals.

3. AUC over a pre-defined steady state interval such as 24 h which does not need to be the same as the Dose Interval (e.g. AUCss24). If you change the Dose Interval there is no need to change the target value.

4. Cumulative AUC over an interval such as 4 days which may include several doses (e.g. Cum AUC 4 days). If you change the Dose Interval there is no need to change the target value.

5. Steady state value at a specific time after the dose such as 12 h (e.g. C12h). If you use a Dose Interval that is the same as this time after dose then the target is the steady state trough concentration.

iii. Dose Interval: The predicted dose will is based on the dosing interval specified in this option. It is recommended to use a Dose Interval that corresponds to the typical dosing interval you are planning to use.

iv. Calculation Comment: This option can be used to provide a comment on the dose prediction calculation.

b. Click on Calculate (blue button) to see the Dose Predictions

Figure 6

6. The FirstDose step -- predict an initial dosing scheme by clicking on Results (top menu). You can only use this before you enter any Dose or Concentration observations in the Doses & Observations table.

Figure 7

and Calculate (blue button) (use the default choices until you get more comfortable). The “What if” option is there so you can explore Dose predictions and get a visual reminder that the dose calculation was not based on actual doses and observations.

a. You will see dosing recommendations (loading dose and maintenance dose) and a graph of predicted values such as concentrations. Note that there is a warning about renal function. This is because no serum creatinine observation was entered and therefore renal function has been assumed to be 1 (normal for this patient’s weight and age).

Figure 8

b. The dosing recommendations and graph are based on the patient details and basic observations you entered.

7. Return to the Doses and Observations page. Enter one or more doses. Be sure to enter a suitable date and time for each dose. When given by infusion you should enter the infusion duration. If you know a similar dose has been repeated at regular intervals you can use the Repeat option to specify the number of doses and dosing interval.

Figure 9

8. The NexDose step – When you have observations such as drug concentration or INR you can use the Results menu item to predict doses based on the observations.

a. Enter one or more response observations. It is important that you enter the date and time of the observations correctly relative to the previous dose(s).

Figure 10

Figure 11

b. Click on the Results menu item. After a brief calculation delay you will see dosing recommendations (maintenance dose) and a graph of predicted values such as concentrations. If you have chosen an AUC target type the steady state average concentration equivalent to the target AUC and dosing interval is shown as well as the AUC target.

Figure 12

9. Each time you change the doses, basic or response observations a new instance of the patient data is created. Each instance can be accessed through the menu of dates and times on the left hand side of the NextDose window. They are colour coded to show instances based on actual data (green), what if data (red) or changed data that has not been used for a calculation yet (orange).