Review
Health-related quality of life assessment and reported outcomes in leukaemia randomised controlled trials – A systematic review to evaluate the added value in supporting clinical decision making

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Abstract

Health-related quality of life (HRQOL) is increasingly reported as an important outcome in cancer clinical trials. However, very little evidence exists on the impact of such evaluation in randomised controlled trials (RCTs) of leukaemia patients. A systematic search of the literature from 1980 to 2007 was undertaken and studies were identified and evaluated independently, according to a pre-defined coding scheme, by three reviewers. Both HRQOL outcomes and traditional clinical reported outcomes were systematically analysed to evaluate their consistency and their relevance for supporting clinical decision making. Nine RCTs were identified, involving 3838 patients overall. There were four RCTs involving acute myeloid leukaemia patients (AML), three with chronic myeloid leukaemia (CML) and two with chronic lymphocytic leukaemia (CLL). Six studies were published after 2000 and provided fairly robust methodological quality. Imatinib greatly improved HRQOL compared to interferon based treatments in CML patients and fludarabine plus cyclophosphamide does not seem to have a deleterious impact on patient’s HRQOL when compared to fludarabine alone or chlorambucil in CLL patients. This study revealed the paucity of HRQOL research in leukaemia patients. Nonetheless, HRQOL assessment is feasible in RCTs and has the great potential of providing valuable outcomes to further support clinical decision making.

Introduction

Health-related quality of life (HRQOL) assessment in cancer research has become critical to fully evaluate overall treatment effectiveness by also formally including the patient’s perspective as an important objective. Major cancer societies have been supporting its use as a key outcome for more than two decades1 and large Clinical Trial Groups routinely consider including HRQOL assessment in new phase III trial protocols.2

Including HRQOL as an endpoint in cancer clinical trial protocols can provide additional and valuable data to facilitate clinical decision making.3, 4 Recent evidence has shown a considerable amount of clinical trials conducted with a HRQOL component in major solid tumours (i.e. breast, colorectal, non-small cell lung and prostate cancer) also indicating a methodological quality improvement over time.5 The issue of different treatment options in oncology therapies increasingly challenges healthcare managers to provide patients with the best available options and HRQOL outcomes, including functional status, symptom severity and symptom impact, might provide unique information. However, a number of challenging issues deserve thoughtful consideration when designing HRQOL assessment into trial protocols and reporting results. These range from the accurate selection of the most appropriate instrument for the particular trial objective, to the handling of missing data and accurate interpretation of outcomes.6, 7, 8 All these issues are of paramount importance as, if not fully addressed, they might hinder a critical appraisal of outcomes. Recently, Appelbaum and colleagues, while acknowledging the important role of HRQOL assessment in haematological research, also clearly indicated several drawbacks that have hampered, for example, HRQOL being used as a valid endpoint in establishing the efficacy of new agents in the treatment of acute leukaemia.9

While previous work has investigated the added value and the methodological quality of HRQOL assessment in randomised controlled trials (RCTs) of patients with solid tumours including breast,10 brain,11 colorectal,12 lung,13 and prostate cancer,14 no similar systematic evidence exists to date in patients with leukaemia. Recent work suggested the paucity of HRQOL research in patients with chronic lymphocytic leukaemia (CLL)15, 16, 17 or acute myeloid leukaemia (AML),18 and quantification of studies conducted in this area, compared to the amount of research available in major solid tumours, is also lacking.

HRQOL might be greatly impaired in leukaemia patients, particularly those just after diagnosis and during the course of therapy,18 and key symptoms such as fatigue might have a major role in determining patients’ overall HRQOL.19, 20, 21 HRQOL of leukaemia patients might also be particularly impaired because of the aggressive treatments required by some leukaemia diagnoses such as AML. In addition, number of blood transfusions, haemorrhages, days with fever, days on antibiotics, and days spent in hospital can also adversely affect a patient’s HRQOL.

For this reason, the main objective of this systematic review was to evaluate HRQOL methodological quality and the reported outcomes of studies dealing with the effects of new medical treatments tested in a leukaemia RCT setting. In addition, we also explored the possible added value of these studies in supporting clinical decision making.

Section snippets

Search strategy for identification of studies

A literature search for studies meeting the criteria was undertaken on a number of databases by three independent reviewers (FE, BH and GK): PubMed (1980–July 2007), EMBASE (1980–2006), The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2004, Issue 1 and 2) and SCOUPS (1980–2006). The following search criteria was used: leukaemia AND (‘quality of life’ OR QoL OR ‘health status’ OR PRO OR ‘patient reported outcome’ OR HRQL OR HRQoL OR ‘health related quality of

Results

According to the eligibility criteria, nine HRQOL trial-based studies,24, 25, 26, 27, 28, 29, 30, 31, 32 enrolling some 3838 leukaemia patients overall, were identified between 1980 and July 2007 (see Table 1, Table 2).

Discussion

The main objective of this article was to evaluate the methodological quality and reported outcomes of RCTs with a HRQOL component in leukaemia patients. By focusing on RCT settings, we also aimed at providing the scientific community with state of the art evidence regarding the impact of newer treatments on patient’s HRQOL and the possible added value of this research in supporting clinical decision making.

Using stated selection and eligibility criteria we found, overall, nine RCTs with HRQOL

Conflict of interest statement

None declared.

Authors contribution

  • Study concept and design: Fabio Efficace, Bernhard Holzner.

  • Acquisition of data: Fabio Efficace, Georg Kemmler, Bernhard Holzner.

  • Analysis and interpretation of data: Fabio Efficace, Georg Kemmler, Marco Vignetti, Franco Mandelli, Stefano Molica, Bernhard Holzner.

  • Drafting of the manuscript: Fabio Efficace, Georg Kemmler, Bernhard Holzner.

  • Critical revision of the manuscript for important intellectual content: Fabio Efficace, Georg Kemmler, Marco Vignetti, Franco Mandelli, Stefano Molica, Bernhard

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    Presented in part at the 14th Annual Conference of the International Society for Quality of Life Research (ISOQOL), Toronto, Canada, October 10–13, 2007.

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