Calculate morphine milligram equivalents (MME) for a single study participant

Calculates the single-day MME and total MME for each individual prescription opioid medication submitted for calculation. Also calculates total MME, total days of supply, and four distinct Total MME/Day calculations from the NIH HEAL Online MME Calculator across all prescription medications for two different medication groupings: 1) opioids without buprenorphine and 2) opioids with buprenorphine.

Usage

# S3 method for class 'list'
calculate_mme(x, therapy_days, observation_window_days, use_api = TRUE, ...)

Arguments

x

(list)
A list of medications. Each element must be a nested list containing each of the following fields:

medication_name: a string matching an API-accepted medication name and its dosage units. To see a full list of API-accepted values, run get_med_list().
dose: a positive number indicating the dose of the associated opioid medication listed in the medication_name field. Units of dose should match the units listed in medication_name.
doses_per_24_hours: a positive number indicating the number of doses in 24 hours.
days_of_medication: a positive number indicating the duration of the opioid medication prescription listed in the associated medication_name in days.

therapy_days

(numeric)
Either a single positive number or a vector of two positive numbers indicating the sum of prescription duration (days) for each medication, but with each calendar day counted only ONCE. When a single number is provided, it is used for the both the "with buprenorphine" and "without buprenorphine" MME calculations; when a vector of 2 numbers is provided (e.g., c(10, 18)) then the first and second numbers in the vector are used for the "with buprenorphine" and "without buprenorphine" MME calculations, respectively. This is the denominator for MME/Day definition 2.

If there is only one prescription or if there is no calendar overlap (i.e., no days on which more than one prescription is active) this will be the same as the total days supply returned by the calculator API (total_days).
If there are overlapping prescriptions, this is the number of unique calendar days.

observation_window_days

(numeric)
Either a single positive number or a vector of two positive numbers indicating a study-defined fixed observation window of time. Typical choices are 7 day, 14 day, 30 day, 90 day. When a single number is provided, it is used for the both the "with buprenorphine" and "without buprenorphine" MME calculations; when a vector of 2 numbers is provided (e.g., c(7, 30)) then the first and second numbers in the vector are used for the "with buprenorphine" and "without buprenorphine" MME calculations, respectively. This is the denominator for MME/Day definition 3.

use_api

(logical)
Indicates whether to use the NIH HEAL Online MME Calculator API (default) to perform calculations or perform them locally instead (FALSE). Setting to FALSE allows the user to perform the same calculations without being restricted by the Online MME Calculator API rate limit of 50 patient calculations per 15 minutes and also allows the user to perform the calculations without relying on internet access.

...

These dots are for future extensions and must be empty.

Value

A list of MME calculations. Will error if any medications are invalid or if any numeric parameters are not positive numbers.

Details

The function will provide the same results regardless of whether the user has specified they want calculation done using the API (use_api). Specifying use_api == FALSE helps overcome the online calculator API rate limit of 50 (patient-level) requests per 15 minutes. In addition to returning user-specified arguments, calculate_mme() also returns several other variables mentioned in the Description section. Output variable description details are below; see Adams, et al. (2025) for a comprehensive overview.

Prescription-Level

Conversion Factor for <medication_name> (factor): the conversion factor used for calculating total MME/day.

MME for <medication_name> (mme): Morphine milligram equivalent for the whole prescription specified in medication_name, calculated as (dose) * (doses_per_24_hours) * (factor) * (days_of_medication).

24h MME for <medication_name> (single_day_mme): Morphine milligram equivalent for the prescription specified in medication_name for a single day, calculated as (dose) * (doses_per_24_hours) * (factor).

One day: Typically, the day with highest opioid exposure is entered, and the sum of 24-hour MME across the drugs that apply to this day is calculated. Highest MME in one day is definition 4.

Summary-Level:

On-therapy Days (therapy_days): The sum of prescription duration (days_of_medication) for each medication, but with each calendar day counted only ONCE. User-supplied; this is the denominator for MME/Day definition 2.

If there is only one prescription, or if there is no calendar overlap (no days on which more than one prescription is active), this will be the same as the total days supply.
If there are overlapping prescriptions, this is the number of unique calendar days.

Total MME (total_mme): The MME for each medication, summed across all prescriptions. This is the numerator for MME/Day definitions 1, 2, and 3.

Total Days Supply (total_days): The sum of the entered prescription duration (days_of_medication) for each of the medications (Med 1 duration + med 2 duration...). Automatically calculated. This is the denominator for MME/Day definition 1.

MME/Day

MME/Day is an aggregate measure, calculating the total MME divided by a specified time window (a number of days). The MME/Day definitions specify the number of days:

MME/Day Definition 1 (mme1): Total Days Supply

MME Definition 1 = Total MME / Total Days Supply time window (sum of entered prescription durations).

mme1 = total_mme / total_days

Note that the same calendar day may contribute multiple times, if overlapping prescriptions.
Reason to select this definition: This is the least complicated calculation; appears best suited when immediate-release opioids are prescribed for short discrete times.
Identified challenge with this definition: It consistently underestimated MME per day when overlapping prescriptions were present or when immediate-release and extended release opioids were prescribed concurrently.

MME/Day Definition 2 (mme2): On-therapy Days

MME Definition 2 = Total MME / On-therapy Days time window (sum of entered prescription durations except each calendar day is counted only ONCE).

mme2 = total_mme / therapy_days

Note - On-therapy Days unique calendar days.
Reason to select this definition: Provides a smoothed measure useful in studies of dose-dependent adverse effects, including opioid-induced constipation or overdose in patients with opioid tolerance or who have been stable on opioids.
Identified challenge with this definition: The metric is time-varying and affords the greatest flexibility to define medication gap periods and leftover/unused medications to improve pharmacoepidemiologic studies.

MME/Day Definition 3 (mme3): Fixed Observation Window

Uses the Total MME study-specified fixed observation window. MME Definition 3 = Total MME / Number of days in observation window:

mme3 = total_mme / observation_window_days

If this definition is selected, it is important to report on the duration of the fixed window.
Reason to select this definition: Most suitable for studies with a known or suspected duration of risk during which adverse events are expected to occur, such as incidence of opioid use disorder. This definition may be useful when prescriptions are filled at irregular time intervals on a as needed basis (pro re nata, PRN).
Identified challenge with this definition: The definition consistently had the lowest milligrams per day for immediate-release opioids. It is the most robust to misspecification, amenable to transformations, and has the least noise when constructing continuous functions. However, since it assumes uniform exposure/risk within a window, there is less scope for time-varying adjustment.
This is the definition recommended by the Department of Health and Human Services Office of the Inspector General.

MME/Day Definition 4 (mme4): Maximum Daily Dose

Uses the sum of 24-hour MME for the day with highest opioid exposure.

MME Definition 4 = Drug 1 (dose (mg) x # of doses per day) x conversion factor + Drug 2 (dose (mg) x # of doses per day) x conversion factor + ...

mme4 = sum(dose * doses_per_24_hours * factor)

Report the highest single-day exposure.
Reason to select this definition: A toxicological perspective may be appropriate for patients with no opioid tolerance and in the presence of comorbidities for respiratory depression. It appears to be best suited for immediate dose-dependent toxic effects, such as respiratory depression.
Identified challenged with this definition: This definition may have limited use if it includes opioids where fatal toxicity does not involve respiratory depression (e.g., tramadol) or have atypical mu-opioid receptor agonism (e.g., tapentadol, buprenorphine).
The definition assumes uniform risk of adverse outcomes regardless of time on-therapy. More so than the others, this definition is prone to influence from early refills, unused medication, and how the 90 MME threshold is operationalized.
This definition underlies the algorithm embedded in the CDC Opioid Guideline mobile app. There may be difficulty reconciling findings with studies using the other definitions because it returns a MME per day that is significantly higher.
This calculator sums the 24-hour MME for every prescription, without considering calendar dates.

Examples

# Recreating example from Adams MCB, et al. 2025 supplement
#     https://links.lww.com/PAIN/C213
meds_list <- list(
  list(
    medication_name = "Morphine (mg)",
    dose = 5,
    doses_per_24_hours = 4,
    days_of_medication = 7
    ),
  list(
    medication_name = "Morphine (mg) LA",
    dose = 10,
    doses_per_24_hours = 3,
    days_of_medication = 30
    )
)

# Using API
calculate_mme(meds_list, 30, 90)
#> $message
#> [1] "Processed medications"
#> 
#> $therapy_obs_window_with
#> $therapy_obs_window_with$therapy_days
#> [1] 30
#> 
#> $therapy_obs_window_with$observation_window_days
#> [1] 90
#> 
#> 
#> $therapy_obs_window_without
#> $therapy_obs_window_without$therapy_days
#> [1] 30
#> 
#> $therapy_obs_window_without$observation_window_days
#> [1] 90
#> 
#> 
#> $medications
#>    medication_name dose doses_per_24_hours days_of_medication factor mme
#> 1    Morphine (mg)    5                  4                  7      1 140
#> 2 Morphine (mg) LA   10                  3                 30      1 900
#>   single_day_mme
#> 1             20
#> 2             30
#> 
#> $mme_definitions
#> $mme_definitions$with_buprenorphine
#>   total_mme total_days     mme1     mme2     mme3 mme4
#> 1      1040         37 28.10811 34.66667 11.55556   50
#> 
#> $mme_definitions$without_buprenorphine
#>   total_mme total_days     mme1     mme2     mme3 mme4
#> 1      1040         37 28.10811 34.66667 11.55556   50
#> 
#> 

# Not using API
calculate_mme(meds_list, 30, 90, use_api = FALSE)
#> $message
#> [1] "Processed medications (local calculation)"
#> 
#> $therapy_obs_window_with
#> $therapy_obs_window_with$therapy_days
#> [1] 30
#> 
#> $therapy_obs_window_with$observation_window_days
#> [1] 90
#> 
#> 
#> $therapy_obs_window_without
#> $therapy_obs_window_without$therapy_days
#> [1] 30
#> 
#> $therapy_obs_window_without$observation_window_days
#> [1] 90
#> 
#> 
#> $medications
#>    medication_name dose doses_per_24_hours days_of_medication factor mme
#> 1    Morphine (mg)    5                  4                  7      1 140
#> 2 Morphine (mg) LA   10                  3                 30      1 900
#>   single_day_mme
#> 1             20
#> 2             30
#> 
#> $mme_definitions
#> $mme_definitions$with_buprenorphine
#>   total_mme total_days     mme1     mme2     mme3 mme4
#> 1      1040         37 28.10811 34.66667 11.55556   50
#> 
#> $mme_definitions$without_buprenorphine
#>   total_mme total_days     mme1     mme2     mme3 mme4
#> 1      1040         37 28.10811 34.66667 11.55556   50
#> 
#> 

# Clean up meds_list
rm(meds_list)