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The use of patient-reported outcomes instruments in registered clinical trials: Evidence from ClinicalTrials.gov

https://doi.org/10.1016/j.cct.2009.02.005Get rights and content

Abstract

Background

Investigators of clinical trials in which the list of outcomes include patient-reported outcomes (PROs) – usually labeled quality of life (QoL) – have a large number of instruments from which to choose. The extent and manner in which PRO instruments are used in clinical trials can be assessed using data from clinical trial registries. Most medical journals now require a clinical trial be registered before its results are considered for publication. This requirement is intended to discourage publication bias, such as the reporting of tests of hypotheses different from those stipulated at the start of the trial and selective reporting of partial results.

Purpose

To assess the usage of PRO instruments in registered trials by various trial characteristics and to determine if the instruments are adequately identified in the registry.

Methods

A local copy of the ClinicalTrials.gov database was made in September 2007. The outcomes of all interventional trials registered since September 2004 were assessed for usage of a PRO instrument. Odds ratios of PRO usage were estimated by a logistic regression model.

Results

Of 17,704 interventional trials, 2481 (14.0%) used at least one PRO instrument. However, less than half of those trials (41.0%) identified the instrument to be used. PRO usage is positively associated with phase (III), randomization type (randomized), intervention type (behavior) and sponsorship type (university/research organization).

Conclusions

PRO instruments are used in a significant percentage but minority of clinical trials. Trial registries should require that all PRO instruments be identified, including the concepts or outcomes they are intended to measure.

Introduction

Patient-reported outcome (PRO) instruments, i.e. questionnaires to be completed by the trial participants, are used in clinical trials to assess how a patient feels. Although PRO includes any patient-reported outcome, indexes have long used “quality of life” (QoL) in classification of published reports [1]. The increasing importance of PRO's in the assessment of clinical trial outcomes is demonstrated by the establishment of initiatives such as the Patient-Reported Outcomes Measurement Information System (PROMIS) [2] and guidance on the usage of PRO instruments from the U.S. Food and Drug Administration (FDA) [3] (Table 1).

Reviews of published reports of clinical trials, however, have found that only a small percentage of trials use PRO instruments. From a review of the Cochrane Controlled Trials Register, Sanders et al. [4] found that from 1980 to 1997 no more than 4.2% reported measures of QoL in all disciplines and no more than 8.2% of cancer trials reported measures of QoL. Gotay and Wilson [5] found that only 7% of trials published in the Journal of Clinical Oncology between 1992 and 1996 included PRO assessments. A more recent review of abstracts in PubMed by Naito et al. [6] found that only 4.4% of trial results published from 2000–2003 assessed QoL. As with the Sanders et al. study, Naito et al. found that the most common condition assessed for QoL was cancer.

The fact that all of these studies relied on published reports of clinical trials is possibly a common deficiency. From a review of registered clinical trials of cancer treatments, Ramsey and Scoggins [7] found that the results of only 17% of completed trials are published in peer-reviewed journals. Consequently, assessments of PRO usage in clinical trials from peer-reviewed articles could suffer from publication bias. Furthermore, it can take several years from the start of a clinical trial to the publication of its results. So even reviews of relatively recent publications might reflect the choices made by clinical trial investigators from many years in the past.

Ramsey and Scoggins based their conclusion from examination of data from ClinicalTrials.gov, a U.S. government-managed registry of clinical trials. Since the announcement on clinical trial registration by the International Committee of Medical Journal Editors (ICMJE), all major medical journals have made registration of clinical trials before the start of participant enrollment a precondition for publication of trial results [8]. The announcement was published in September 2004, but the final deadline for registration of trials already started was in September 2005. This concerted effort was made in the hopes that it would deter the kind of publication bias that occurs when outcome measures of trial results are selectively reported [9], [10]. Therefore there is an emphasis on pre-accrual registration of the trial's outcome measurements.

ClinicalTrials.gov, by far the largest registry of clinical trials in the world with 17,704 interventional clinical trials registered between September 1, 2004 and September 1, 2007, provides information on each trial's sponsor, enrollment and design features, including its primary and secondary outcomes [11], [12]. Consequently it provides a source of information with which to make an unbiased and timely assessment of PRO instrument usage in clinical trials.

Section snippets

Methods

In September 2007 a local copy of the entire ClinicalTrials.gov website was made. The study adopted the sponsor type classification by the registry: industry, university/research organization, National Institutes of Health (NIH), federal government (not NIH), network and other (foreign) government.

Any trial registrations that contained either “quality of life”, “qol”, “patient-reported outcome”, “health status”, “patient satisfaction” or “psychometric” were examined to determine if they were

Results

Of 17,704 interventional trials registered between September 2004 and September 2007, 2,481 (14.0%) stated that a PRO was one of the outcomes. Trials sponsored by university/research organizations were more likely to measure PRO than the other major sponsor types, i.e. commercial firms and the National Institutes of Health (OR: 1.12, 95% CI: 1.01–1.23). So were the remaining sponsor types, mostly networks of research centers (OR: 1.25, 95% CI: 1.09–1.45). Some trials were sponsored by more than

Comment

The usage of PRO instruments in clinical trials is considerably greater than reported in previous studies. The difference is even greater when the information on which the earlier studies are based is considered. The characteristics of trials which are positively associated with publication, namely randomized phase III trials sponsored by non-commercial organizations, are also positively associated with PRO usage. So the 4% of published trials that assessed QoL in years past appears even

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