Measuring disease-specific quality of life in clinical trials.

While measurement of quality of life is a vital part of assessing the effect of treatment in many clinical trials, a measure that is responsive to clinically important change is often unavailable. Investigators are therefore faced with the challenge of constructing an index for a specific condition or even for a single trial. There are several stages in the development and testing of a quality-of-life measure: selecting an initial item pool, choosing the "best" items from that pool, deciding on questionnaire format, pretesting the instrument, and demonstrating the responsiveness and validity of the instrument. At each stage the investigator must choose between a rigorous, time-consuming approach to questionnaire construction that will establish the clinical relevance, responsiveness and validity of the instrument and a more efficient, less costly strategy that leaves reproducibility, responsiveness and validity untested. This article describes these options and outlines a pragmatic approach that yields consistently satisfactory disease-specific measures of quality of life.     

Measuring quality of life in clinical trials: a taxonomy and review.

Measurement of quality of life is becoming increasingly relevant to controlled clinical trials. Two basic types of instrument are available: generic instruments, which include health profiles and utility measurements based on the patient's preferences in regard to treatment and outcome; and specific instruments, which focus on problems associated with individual diseases, patient groups or areas of function. The two approaches are not mutually exclusive; each has its strengths and weaknesses and may be suitable under different circumstances. We surveyed 75 randomized trials published in three medical journals in 1986 and categorized them according to the importance of quality of life as a measure of outcome and the extent to which quality of life was actually measured. Although a number of the investigators used quality-of-life instruments in a sophisticated manner, in only 10 of 55 trials in which the measurement had been judged to be crucial or important were instruments with established validity and responsiveness used. We conclude that although accurate measurement of quality of life in randomized trials is now feasible it is still not widely done. Using the framework we have outlined, investigators can choose generic or specific instruments according to the purpose and the focus of their trial.     

Standards for the use of ordinal scales in clinical trials

Ordinal scales are frequently used in clinical trials to quantify outcomes which are non-dimensional. They may be regarded as either single state or transition measures based on whether they assess the outcome at a single point in time or directly examine change which has occurred between two points in time. Each has unique structural and operating characteristics, so that different methodological standards for their construction and utilisation are required. All trials employing ordinal scales published in three leading journals between 1980 and 1984 were examined. For both types of scales the individual ranks must be clearly defined, mutually exclusive, and ordered in a hierarchical progression. Further, both types must be able to detect equally both improvement and deterioration. For this to be ensured with the single state scales the population under study must not be clustered at one extreme of the scale at entry into the trial. With the transition scales internal symmetry must be achieved. Strategies for determining the comparisons to be performed should include emphasis on within patient analysis for crossover trials. Concordance between scale scores and the other measures of outcome employed in the trial must be evaluated. Frequent violations were uncovered in the studies reviewed, and it is hoped that the simple rules outlined will prove useful in the planning and evaluation of future trials.     

Measuring health-related quality of life in clinical trials that evaluate the role of chemotherapy in cancer treatment

Quality of life is a subjective multidimentional concept that can be assessed by means of validated questionnaires completed by patients. The psychological effects of a diagnosis of cancer and the physical effects of the disease and its treating have a major impact on a patient's health-related quality of life. Much cancer treatment, especially chemotherapy for metastatic disease, is given for palliation. Palliation implies improvement in either the duration or quality of life remaining. However, treatment patients with common metastatic tumours to prolong life is generally unsuccessful, so improving quality of life is a more realistic goal. Most trials involve evaluating shrinkage of a tumour (i.e., tumour response), which does not imply a benefit to the patient. Few trials have assessed quality of life directly, although several validated instruments, described here, are available to quantify quality of life in cancer patients. These instruments represent a wide scope, from evaluating general health to assessing the quality of life of patients with specific types and stages of cancer. They respond to changes in clinical state and are strongly predictive of survival. Measures of quality of life should be incorporated in all clinical trials where treatment is palliative, and a simple, relevant measure of quality of life should be used as a (or the) primary outcome measure. Other measures of quality of life are important to ensure that gains in one area do not occur at the expense of others. A few large trials incorporating these principles have shown that chemotherapy can provide palliation for patients with advanced cancer.     

The hazards of scoring the quality of clinical trials for meta-analysis.

CONTEXT: Although it is widely recommended that clinical trials undergo some type of quality review, the number and variety of quality assessment scales that exist make it unclear how to achieve the best assessment. OBJECTIVE: To determine whether the type of quality assessment scale used affects the conclusions of meta-analytic studies. DESIGN AND SETTING: Meta-analysis of 17 trials comparing low-molecular-weight heparin (LMWH) with standard heparin for prevention of postoperative thrombosis using 25 different scales to identify high-quality trials. The association between treatment effect and summary scores and the association with 3 key domains (concealment of treatment allocation, blinding of outcome assessment, and handling of withdrawals) were examined in regression models. MAIN OUTCOME MEASURE: Pooled relative risks of deep vein thrombosis with LMWH vs standard heparin in high-quality vs low-quality trials as determined by 25 quality scales. RESULTS: Pooled relative risks from high-quality trials ranged from 0.63 (95% confidence interval [CI], 0.44-0.90) to 0.90 (95% CI, 0.67-1.21) vs 0.52 (95% CI, 0.24-1.09) to 1.13 (95% CI, 0.70-1.82) for low-quality trials. For 6 scales, relative risks of high-quality trials were close to unity, indicating that LMWH was not significantly superior to standard heparin, whereas low-quality trials showed better protection with LMWH (P<.05). Seven scales showed the opposite: high quality trials showed an effect whereas low quality trials did not. For the remaining 12 scales, effect estimates were similar in the 2 quality strata. In regression analysis, summary quality scores were not significantly associated with treatment effects. There was no significant association of treatment effects with allocation concealment and handling of withdrawals. Open outcome assessment, however, influenced effect size with the effect of LMWH, on average, being exaggerated by 35% (95% CI, 1%-57%; P= .046). CONCLUSIONS: Our data indicate that the use of summary scores to identify trials of high quality is problematic. Relevant methodological aspects should be assessed individually and their influence on effect sizes explored.     

Measuring the quality of editorial peer review

Context  The quality of a process can only be tested against its agreed objectives. Editorial peer-review is widely used, yet there appears to be little agreement about how to measure its effects or processes. Methods  To identify outcome measures used to assess editorial peer review as performed by biomedical journals, we analyzed studies identified from 2 systematic reviews that measured the effects of editorial peer review on the quality of the output (ie, published articles) or of the process itself (eg, reviewers' comments). Results  Ten studies used a variety of instruments to assess the quality of articles that had undergone peer review. Only 1, nonrandomized study compared the quality of articles published in peer-reviewed and non–peer-reviewed journals. The others measured the effects of variations in the peer-review process or used a before-and-after design to measure the effects of standard peer review on accepted articles. Eighteen studies measured the quality of reviewers' reports under different conditions such as blinding or after training. One study compared the time and cost of different review processes. Conclusions  Until we have properly defined the objectives of peer-review, it will remain almost impossible to assess or improve its effectiveness. The research needed to understand the broader effects of peer review poses many methodologic problems and would require the cooperation of many parts of the scientific community.      

青少年特发性脊柱侧凸相关生活质量评价量表现状

青少年特发性脊柱侧凸（adolescent idiopathic scoliosis, AIS）是脊柱侧凸当中最常见的疾病,对患者造成生理和心理的双重打击。在生理上,患者的心肺功能受损、严重时可并发多种疾病,女性患者影响其胸部发育,严重时甚至影响生育等;在心理上,AIS引起身体外观畸形,可引起青少年自闭症、抑郁症等心理问题。近年来,对于AIS患者的生存质量评价越来越被临床工作者所重视,在临床中评价患者生存质量的量表是治疗和预后AIS中的重要一环。本文主要综述临床中常用的几种健康相关生存质量评估量表,对其评估内容、信效度及其发展进行简要概述,并论述其在临床中的应用。     

改进中药临床试验报告的参考条目

为改进中药临床试验报告质量，本文在《草药随机对照临床试验的报告：CONSORT声明细则》的基础上，结合中医药的特点，制定了中药临床试验报告的参考条目。本条目沿用了草药CONSORT声明的22项要求，对其中11项的部分内容根据中医药特点进行了细化和增减，并根据中成药和汤药两大类临床试验的特点，争别对参考条目进行细化；最目突出了受试者（participant）、干预措施（intervention）、对照（control）和结局（outcome）四个方面的内容。制定中药临床武验报告的参考条目旨在提高中药临床试验报告的质量，并为杂志编辑和审稿人员提供参考。     

提高中草药随机对照试验的质量Ⅲ:中草药的质量控制

目的:通过对中草药临床随机对照试验中有关中草药质量控制的方法进行分析评价,探讨如何实施中草药临床试验的药物质量控制。方法:文献检索2005年7月前发表于Cochrane图书馆的中草药系统评价共11篇,包含167个中草药临床随机对照试验,实证分析中草药临床试验中有关中草药质量控制的方法。结果:在纳入分析的167个中草药临床随机对照试验中,所采用的中草药制剂类型共有11种,其中只有1个临床随机对照试验提及中药的质量控制方法。结论:在中草药临床随机对照试验过程中,中草药的质量控制是一个非常薄弱的环节。建议:在中草药临床随机对照试验过程中,必须提高中草药的质量控制意识及建立中草药质量控制的技术平台,整合包括中药材生产质量管理规范(Good Agricultural Practice,GAP)、药物生产质量管理规范(Good Manufacturing Practice,GMP)、药物临床试验质量管理规范(Good ClinicalPractice,GCP)以及中药指纹图谱等技术,建立系统控制临床试验药物的质量控制体系。     

Designing clinical protocols for optimal use: Measuring attributes of treatment and cancer control trials

The design of clinical protocols is an important factor in assuring patient accrual and compliance. This paper describes the methods used to assess the attributes of treatment and cancer control research protocols. Measures are presented for assessing three attributes considered important: relative advantage, complexity, and compatibility.     

疾病特异性量表与SF36量表对支气管哮喘患者生命质量评估的比较

目的了解支气管哮喘生命质量量表(AQLQ)在评估支气管哮喘患者生命质量时的效果,并与非特异性生命质量量表SF36量表比较。方法采用4周非双盲定群研究方法,分别以7分制、5分制支气管哮喘生命质量量表(7AQLQ、5AQLQ)和SF36量表对48例支气管哮喘患者在初诊、治疗2周和4周时进行生命质量评估,随访期间患者每日监测呼气峰流速(PEF)并记哮喘日记。结果48例支气管哮喘患者呼气峰流速平均值占预计值百分比(PEF占预计值%)从初诊的55%,提高到治疗2周后的63%和4周后的66%(P<0.05);7-AQLQ和5-AQLQ总均分分别从初诊的5.5、4.0提高到治疗2周后的6.0、4.3及4周后的6.2、4.4(P<0.01),SF36量表总分虽从初诊的549提高到2周后的567和4周后的576,但差异无统计学意义(P>0.05);AQLQ总均分与PEF占预计值%的相关系数明显高于SF36量表与PEF占预计值%的相关系数。结论在评估支气管哮喘患者生命质量时,AQLQ比SF36量表灵敏。     

谈药物临床试验的质量控制

新药临床试验质量是药品上市后安全、有效的保障,为提高药物临床试验质量,建立有效的质量控制体系,笔者就目前药物临床试验质量控制存在的问题及建议进行讨论,认为药物临床试验质量控制的关键环节在于加强研究者的培训工作,使其从思想上重视药物临床试验;加强药物临床试验的过程管理,确保“三级质控”的实施;加强信息化系统在药物临床试验质量控制中的应用。