ICON Patient Reported Outcomes1 – Example Successful US/EU Label Claims
Product
Jakafi (US)/Jakavi (EU)
FDA approval Nov
2011, EMA approval
Aug 2012.
Elvanse (EU)
EMA approval Feb
2013.
1
Indication
Myelofibrosis
(MF)
Attention deficit
hyperactivity
disorder (ADHD)
Instrument/Endpoint
Modified
Myelofibrosis
Symptom
Assessment Form
(MFSAF) v2.0 diary
Secondary endpoint –
symptom
improvement (Total
Symptom Score)
Type/Mode
PRO - Electronic
daily diary
Parent Report Form
of the Child Health
and Illness Profile –
Child Edition (CHIPCE: PRF)
Secondary endpoint –
Health Related
Quality of Life
(notably the first
ADHD medication
with a HRQL label
claim)
Proxy-completed
(ObsRO)
Formerly Patient Reported Outcomes, Oxford Outcomes
ICON PRO Role/Contribution
All the qualitative work used to develop and
support the instrument (concept elicitation,
cognitive debriefing, usability testing)
Instrument revisions/development following
FDA feedback and cognitive debriefing
Client support at FDA and EMA
meeting/review discussion and submission
documents
Qualitative validation work to support the
instrument
Calculation of minimally important
difference (MID) in scores for the
instrument
Drafting target claim language
Jakafi – FDA Approved Label
“Myelofibrosis symptoms were a secondary endpoint and were measured using the modified
Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 diary. The modified MFSAF is a daily diary
capturing the core symptoms of myelofibrosis (abdominal discomfort, pain under left ribs, night
sweats, itching, bone/muscle pain and early satiety). Symptom scores ranged from 0 to 10 with 0
representing symptoms “absent” and 10 representing “worst imaginable” symptoms. These scores
were added to create the daily total score, which has a maximum of 60.
Table 7 presents assessments of Total Symptom Score from baseline to Week 24 in Study 1
including the proportion of patients with at least a 50% reduction (ie, improvement in symptoms). At
baseline, the mean Total Symptom Score was 18.0 in the Jakafi group and 16.5 in the placebo group.
A higher proportion of patients in the Jakafi group had a 50% or greater reduction in Total Symptom
Score than in the placebo group, with a median time to response of less than 4 weeks.
Figure 2 shows the percent change from baseline in Total Symptom Score for each patient at Week
24 (Jakafi N=129, placebo N=103) or the last evaluation on randomized therapy prior to Week 24 for
patients who did not complete 24 weeks of randomized treatment (Jakafi N=16, placebo N=42).
Results are excluded for 5 patients with a baseline Total Symptom Score of zero, 8 patients with
missing baseline and patients with insufficient post baseline data.
Figure 3 displays the proportion of patients with at least a 50% improvement in each of the individual
symptoms that comprise the Total Symptom Score indicating that all 6 of the symptoms contributed to
the higher Total Symptom Score response rate in the group treated with Jakafi.”
Jakavi – EMA Approved SmPC and Package Leaflet
“Jakavi improves myelofibrosis-associated symptoms and quality of life in patients with myelofibrosis.
In COMFORT-I symptoms of myelofibrosis were captured using the modified MFSAF diary v2.0 as an
electronic diary which subjects completed daily. A significantly larger proportion of subjects in the
Jakavi group achieved a ≥50% improvement from baseline in the week 24 total symptom score
compared with the placebo group (45.9% and 5.3%, respectively, p<0.0001 using the chi-square test).
An improvement in overall quality of life was measured by a validated instrument, the EORTC QLQC30 in both COMFORT-I and COMFORT-II. At week 24 in COMFORT-I the mean change for the
global health status/quality of life score was +12.3 and -3.4 (p<0.0001) for Jakavi and placebo,
respectively.
By blocking the action of certain enzymes … Jakavi can reduce the size of the spleen in patients with
myelofibrosis and relieve symptoms such as fever, night sweats, bone pain and weight loss.”
Elvanse – EMA Approved Label
Section 5.1: “Elvanse showed significant improvement in child achievement in academic performance,
as measured by the Health Related Quality of life instrument, Parent Report Form of the Child Health
and Illness Profile-Child Edition (CHIP-CE:PRF) Achievement Domain. Elvanse demonstrated a
significant improvement from baseline compared to placebo (Elvanse: 9.4 versus Placebo -1.1) with a
mean difference between the two treatment groups of 10.5 (p<0.001).”