relapse_indep_from_bounds: Define relapse-free intervals for PIRA definition.

In msprog: Reproducible Assessment of Disability Course in Multiple Sclerosis

Define relapse-free intervals for PIRA definition.

Description

Organise the given interval bounds into a named list to be given as argument relapse_indep to function MSprog(). The relapse-free intervals may be anchored to (any subset of) the following three data-driven checkpoints.

1. "prec": a visit preceding the event: can be (i) the current baseline, (ii) the last visit before event onset, or (iii) the last visit before event onset with a clinically meaningful score difference from it (i.e., for an outcome x with "higher score" = "worse", the last visit i such that x[event] - x[i] >= delta_fun(x[i]), and same for the confirmation visit).

2. "event": the disability worsening event onset.

3. "conf": an eligible confirmation visit.

Usage

relapse_indep_from_bounds(
  p0 = 0,
  p1 = 0,
  e0 = 0,
  e1 = 0,
  c0 = 0,
  c1 = 0,
  prec_type = "baseline",
  use_end_dates = FALSE
)

Arguments

p0	Days before preceding visit (⁠>=0⁠).
p1	Days after preceding visit (⁠>=0⁠), or NULL.
e0	Days before event onset (⁠>=0⁠), or NULL.
e1	Days after event onset (⁠>=0⁠), or NULL.
c0	Days before confirmation (⁠>=0⁠), or NULL.
c1	Days after confirmation (⁠>=0⁠).
prec_type	Which visit to use as "preceding visit". Must be one of: "baseline": the current baseline. "last": the last visit before event onset. ⁠"last_delta⁠: the last visit before event onset with a clinically meaningful score difference from it – i.e., for an outcome x with "higher score" = "worse", the last visit i where ⁠x[event onset] - x[i] >= delta_fun(x[i])⁠ and x[confirmation] - x[i] >= delta_fun(x[i]).
use_end_dates	If TRUE, only the right bounds e1 and c1 are used, as the left bounds will be defined by the onset-to-end interval of each relapse. This option is only relevant when relapse end dates are provided (see renddate_col argument in MSprog()).

Details

If both ends of an interval are 0 (e.g., if both p0=0 and p1=0), the checkpoint is ignored. To merge two intervals together, set both the right end of the first interval and the left end of the second interval to NULL (e.g., "between baseline and event onset": p1=NULL and e0=NULL). Here are some examples:

• No relapses from 90dd before to 30dd after the event, and from 90dd before to 30dd after confirmation [1]:
  relapse_indep_from_bounds(e0=90,e1=30,c0=90,c1=30).

• No relapses between baseline and confirmation (high-specificity definition from [1]):
  relapse_indep_from_bounds(p0=0,p1=NULL,e0=NULL,e1=NULL,c0=NULL,c1=0).

• No relapses from baseline to 30dd after the event, and within confirmation+-30dd [2]:
  relapse_indep_from_bounds(p0=0,p1=NULL,e0=NULL,e1=30,c0=30,c1=30).

Value

A named list to be given as argument relapse_indep to function MSprog().

References

[1] Müller J, Cagol A, Lorscheider J, Tsagkas C, Benkert P, Yaldizli Ö, et al. Harmonizing definitions for progression independent of relapse activity in multiple sclerosis: A systematic review. JAMA Neurol. 2023;80:1232–45.

[2] Kappos L, Wolinsky JS, Giovannoni G, Arnold DL, Wang Q, Bernasconi C, et al. Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol. 2020;77:1132–40.

msprog documentation built on Sept. 4, 2026, 5:08 p.m.