Review
Methodological issues in assessing health-related quality of life of colorectal cancer patients in randomised controlled trials

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Abstract

Although health-related quality of life (HRQOL) is increasingly reported as an important endpoint in cancer clinical trials, questions still remain about the quality of its reporting. The aim of this study was to evaluate the level of reporting of HRQOL in randomised controlled trials (RCTs) of colorectal cancer (CRC). A systematic literature search from 1980 to March 2003 was undertaken on a number of databases. Identified eligible studies were selected and then evaluated on a broad set of HRQOL predetermined criteria by four reviewers. Thirty-one randomised controlled trials involving 9683 colorectal cancer patients were identified. Nearly all studies dealt with metastatic patients and principally compared different chemotherapy regimens. The HRQOL tool most often used was the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), which was used in 48% of the studies. Some methodological limitations were identified: 39% of the RCTs did not report HRQOL compliance at baseline and 52% did not give details on missing data. A rationale for using a specific HRQOL measure was given in only 10% of the studies. Whilst HRQOL assessment is a potential valuable source of information in understanding the impact of colorectal cancer, a number of methodological shortcomings have to be further addressed in future studies.

Introduction

Colorectal cancer (CRC) is one of the most common malignancies in the world and it is the second leading cause of cancer death in Western countries. Surgical resection of the primary tumour is attempted in up to 80% of patients and approximately half of these will be cured. Survival after surgery may be extended with postoperative chemotherapy and there is evidence that neoadjuvant radiotherapy reduces local recurrence after rectal excision [1]. Patients with metastatic CRC may be offered a variety of chemotherapies, although survival benefits are modest [2]. Hepatic resection of isolated liver metastases is increasing and there are a number of ablation techniques for local control of colorectal liver metastases. These treatments are traditionally evaluated with objective clinical endpoints, such as survival and operative morbidity and mortality. Such information is essential to inform decision-makers, but more and more studies in cancer clinical research report health-related quality of life (HRQOL) data [3]. This is important, particularly when survival gains are low.

There are several valid measures of HRQOL that are suitable to use in patients with CRC 4, 5. Although these instruments are widely available, there are many methodological issues that need to be addressed when HRQOL questionnaires are included in a clinical trial 6, 7. Consideration of the likely impact of the new treatment on HRQOL is required. Depending upon the research question, the mode of questionnaire administration may become an important issue, especially for large multicentre trials collecting sensitive data (e.g. sexual function after surgery). The timing of HRQOL measurements is also critical as some treatment symptoms may be missed with incorrect assessment points. Methods of HRQOL data analysis have different challenges often because of the repeated nature of multiple assessment points and concerns with missing data. When including HRQOL in clinical trials, measurement of HRQOL needs to be performed with a clinically appropriate questionnaire with good measurement properties. Unless standards for measuring HRQOL are adhered to in clinical trials, the data that are collected will be difficult to interpret and unlikely to make clinical sense. Despite a growing literature highlighting these principals, many studies in CRC do not address such concerns [8]. Previous review on randomised controlled clinical trials (RCTs) including an HRQOL evaluation in different cancer sites, such as prostate, brain, lung and breast, have shown overall a number of methodological shortcomings 9, 10, 11, 12, 13.

Although reviews exist on HRQOL aspects in CRC patients, to date, no detailed systematic reviews have been performed on HRQOL methodology used in RCTs. Furthermore, the issue of poor quality trials has been highlighted as a limiting factor for using HRQOL outcomes in the drugs approval process 14, 15. On these grounds, our aim was to systematically review the quality of HRQOL assessments used in RCTs of treatment for CRC patients.

Section snippets

Review methodology

A literature search was undertaken on the following databases: MedLine (1980–March 2003), the Cochrane Controlled Trials Register (Cochrane Library 2000, Issue 4) and the online National Cancer Institute database. Studies were selected based on the criteria cited below. In addition, significant articles listed as references were also included for possible selection. The search strategy for MedLine and Cochrane databases included the following words: colon, colorectal, rectum, and cancer,

Types of participants

Participants were adult patients (aged 18 years and over) diagnosed with colon or rectal cancer as a primary site of disease regardless of the grade of the tumour stage. Patients undergoing screening procedures were not eligible.

Types of intervention

All RCTs comparing different medical treatment were eligible, regardless of the intervention type—surgical procedures, radiotherapy or chemotherapy. Any studies dealing with psychological intervention or any kind of intervention other than medical treatments were

Methods of evaluation of the studies

Four reviewers independently analysed all identified RCTs, unblinded for the authorship of the article. When disagreement about the analysis of a study occurred, all reviewers revised the paper to reconcile any differences. At the end of the process, all reviewers agreed upon the final classification. The selected trials were mainly evaluated on the level of HRQOL reporting and HRQOL methodology used rather than the overall quality of the trial as such.

In the absence of a gold standard for

Results

According to the eligibility criteria, 31 RCTs assessing HRQOL by means of patient self-reported measures were identified between 1980 and March 2003 (Table 1, Table 2, Table 3, Table 4). Besides these, three other studies were also retrieved, but excluded from trial analyses (with the consensus of all authors). Two of these studies met our criteria, but did not report any details about the methodology used to assess HRQOL 25, 26 and the remaining one was excluded because it was impossible to

Conclusions

The assessment of HRQOL in cancer clinical trials is becoming more widespread and the proportion of studies including such an assessment is rapidly increasing. Nonetheless, previous reports have suggested that the level of HRQOL reporting in cancer clinical research is often poor thus hampering a clear understanding of such assessments for supporting clinical decision-making 9, 10, 11, 12, 13, 60. Hence, the main aim of this systematic review was to examine the reported quality of HRQOL trial

Acknowledgements

Fabio Efficace is supported by the Camilla Samuel Fellowship in memory of Lady Grierson. The authors wish to thank Sheila Sanderson Scott for the review of the manuscript.

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    Presented at the European Cancer Conference, ECCO 12, Copenhagen, Denmark, 21–25 September 2003. The contents of this article are solely the views of the authors and do not necessarily represent the official views of the respective organisations.

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