2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Table 2. Barriers and Solutions to Standard Use of PROs in Clinical Trials
Barrier Solution
Lack of “off-the-shelf ” validated instruments Need to make PROs publically available
Inadvertent unmasking Require a large effect size
Substantiate symptomatic benefits via objective measures (such as radiographic
or serum biomarker responses)
Missing data e-products for data capture, real-time reminders, real-time monitoring, telephone
interviews when patient is too ill to complete PRO
There may be concerns that systematic assessment will document more low
grade toxicities
Additional resources for routine inclusion of PROs in clinical trials for symptom
assessment may be needed since the NCI generally only funds PROs that
answer a specific hypothesis
standard-dose (70.2-Gy) radiation therapy for localized prostate
cancer. A preliminary analysis of the high-dose arm,
comparing 3-dimensional conformal radiotherapy (3DCRT)
and intensity-modulated radiotherapy (IMRT), where each
institution declared its choice of 3DCRT or IMRT before trial
participation, was conducted. A total of 763 patients were
in the high-dose arm and included in the toxicity analysis, 20
and 499 patients (65%) were included in the PRO analysis. 21
Although the CTC version 2.0 toxicity report indicated a
benefit in favor IMRT for grade 2 or higher gastrointestinal
toxicities (22% 3DCRT vs. 15% IMRT, p � 0.039) and in
favor of IMRT for combined gastrointestinal and genitourinary
grade 2 or higher toxicities (15.1% 3DCRT vs. 9.7%
IMRT, p � 0.042), PROs did not corroborate a benefit
patients could note. Corresponding PRO gastrointestinal
and genitourinary variables indicated no substantial differences
between 3DCRT and IMRT. An important difference
that PROs demonstrated in favor of IMRT not found on
PROs better identify baseline symptoms related to disease or prior treatment than
current standard physician toxic effect reporting, making it clearer during a
trial which symptoms are attributable to study drug compared with preexisting
causes
Standard PRO reporting should be viewed no differently than standard CTC(AE)
reporting and routinely incorporated as such
Abbreviations: CTC(AE), Common Terminology Criteria for Adverse Events; NCI, National Cancer Institute; PRO, patient-reported outcome.
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physician reporting was erectile dysfunction; of note, the
IMRT benefit was primarily in men younger than 70 years
(p � 0.04). Given the higher cost of IMRT over 3DCRT for
the treatment of prostate cancer, the PRO data add an
important dimension to the comparative effectiveness equation.
Although the benefits of inclusion of PROs in clinical trials
and the risks of noninclusion have been delineated, there
are some barriers to routine inclusion of PROs in clinical
trials. However, solutions to these barriers exist (Table 2).
Numerous validated PRO instruments with the breadth and
depth to answer hypothesis-specific clinical trial questions
are available, but a more parsimonious method would help
routine inclusion in clinical trials.
A major step forward has been the development of the
PRO version of the CTC-AE (PRO-CTC[AE]). 22 The PRO-
CTC(AE) has been designed to capture a comprehensive
range of symptoms and functioning that enhances monitor-
Fig. 1. Radiation Therapy Oncology
Group (RTOG) outcomes model for guiding
inclusion of patient-reported outcomes
in clinical trials.
Abbreviations: RT, radiation therapy;
PSA, prostate specific antigen; QALYs,
quality-adjusted life years; PROs, patient
reported outcomes.