What surgeons tell patients and what patients want to know before major cancer surgery: a qualitative study.

BACKGROUND: The information surgeons impart to patients and information patients want about surgery for cancer is important but rarely examined. This study explored information provided by surgeons and patient preferences for information in consultations in which surgery for oesophageal cancer surgery was discussed. METHODS: Pre-operation consultations in which oesophagectomy was discussed were studied in three United Kingdom hospitals and patients were subsequently interviewed. Consultations and interviews were audio-recorded, transcribed in full and anonymized. Interviews elicited views about the information provided by surgeons and patients' preferences for information. Thematic analysis of consultation-interview pairs was used to investigate similarities and differences in the information provided by surgeons and desired by patients. RESULTS: Fifty two audio-recordings from 31 patients and 7 surgeons were obtained (25 consultations and 27 patient interviews). Six consultations were not recorded because of equipment failure and four patients declined an interview. Surgeons all provided consistent, extensive information on technical operative details and in-hospital surgical risks. Consultations rarely included discussion of the longer-term outcomes of surgery. Whilst patients accepted that information about surgery and risks was necessary, they really wanted details about long-term issues including recovery, impact on quality of life and survival. CONCLUSIONS: This study demonstrated a need for surgeons to provide information of importance to patients concerning the longer term outcomes of surgery. It is proposed that "core information sets" are developed, based on surgeons' and patients' views, to use as a minimum in consultations to initiate discussion and meet information needs prior to cancer surgery.

Synthesis and summary of patient-reported outcome measures to inform the development of a core outcome set in colorectal cancer surgery.

AIM: Patient-reported outcome (PRO) measures (PROMs) are standard measures in the assessment of colorectal cancer (CRC) treatment, but the range and complexity of available PROMs may be hindering the synthesis of evidence. This systematic review aimed to: (i) summarize PROMs in studies of CRC surgery and (ii) categorize PRO content to inform the future development of an agreed minimum 'core' outcome set to be measured in all trials. METHOD: All PROMs were identified from a systematic review of prospective CRC surgical studies. The type and frequency of PROMs in each study were summarized, and the number of items documented. All items were extracted and independently categorized by content by two researchers into 'health domains', and discrepancies were discussed with a patient and expert. Domain popularity and the distribution of items were summarized. RESULTS: Fifty-eight different PROMs were identified from the 104 included studies. There were 23 generic, four cancer-specific, 11 disease-specific and 16 symptom-specific questionnaires, and three ad hoc measures. The most frequently used PROM was the EORTC QLQ-C30 (50 studies), and most PROMs (n = 40, 69%) were used in only one study. Detailed examination of the 50 available measures identified 917 items, which were categorized into 51 domains. The domains comprising the most items were 'anxiety' (n = 85, 9.2%), 'fatigue' (n = 67, 7.3%) and 'physical function' (n = 63, 6.9%). No domains were included in all PROMs. CONCLUSION: There is major heterogeneity of PRO measurement and a wide variation in content assessed in the PROMs available for CRC. A core outcome set will improve PRO outcome measurement and reporting in CRC trials.

Core information set for oesophageal cancer surgery.

BACKGROUND: Surgeons provide patients with information before surgery, although standards of information are lacking and practice varies. The development and use of a 'core information set' as baseline information before surgery may improve understanding. A core set is a minimum set of information to use in all consultations before a specific procedure. This study developed a core information set for oesophageal cancer surgery. METHODS: Information was identified from the literature, observations of clinical consultations and patient interviews. This was integrated to create a questionnaire survey. Stakeholders (patients and professionals) were surveyed twice to assess views on importance of information from 'not essential' to 'absolutely essential' using Delphi methods. Items not meeting predefined criteria were discarded after each survey and the final retained items were voted on, in separate patient and professional stakeholder meetings, to agree the core set. RESULTS: Some 67 information items were identified initially from multiple sources. Survey response rates were 76·5 per cent (185 of 242) and 54·8 per cent (126 of 230) for patients and professionals respectively (first round), and over 83 per cent in both groups thereafter. Health professionals rated short-term clinical outcomes most highly (technical complications), whereas patients prioritized information related to long-term benefits. The consensus meetings agreed the final set, which consisted of: in-hospital milestones to recovery, rates of open-and-close surgery, in-hospital mortality, major complications (reoperation), milestones in recovery after discharge, longer-term eating and drinking and overall quality of life, and chances of survival. CONCLUSION: This study has established a core information set for surgery for oesophageal cancer.

Patient-reported outcomes in long-term survivors of metastatic colorectal cancer needing liver resection.

BACKGROUND: Five-year survival after hepatic resection for colorectal cancer (CRC) liver metastases is good, but data on patient-reported outcomes are lacking. This study describes the long-term impact of liver surgery for CRC metastases on patient-reported outcomes. METHODS: The study used the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and the disease-specific module, EORTC QLQ-LMC21. For functional scales, mean scores out of 100 with 95 per cent c.i. were calculated; differences of 10 points or more were considered clinically significant. Responses to symptom scales and items were categorized as 'minimal' or 'severe'. Proportions and 95 per cent c.i. for symptoms were calculated. RESULTS: A total of 241 patients were recruited; nine (3·7 per cent) had unresectable disease and were excluded. Some 68 (42 men) of 80 long-term survivors participated; their mean age was 69·5 years and median follow-up was 8·0 (range 6·9-9·2) years. Values for baseline and 1-year patient-reported outcome data were similar. Scores for functional scales were excellent (emotional function: 92, 95 per cent c.i. 87 to 96; social function: 94, 89 to 99; role function: 94, 90 to 98), reflecting clinically significant improvements from baseline values of 17 (10 to 24), 12 (3 to 21) and 12 (3 to 20) respectively. Severe symptoms were uncommon (affected less than 5 per cent of patients) for most patient-reported outcome scales or items, but persistent severe symptoms were noted for sexual function (2 per cent increase from baseline), peripheral neuropathy (2 per cent increase), constipation (10 per cent increase) and diarrhoea (5 per cent increase). CONCLUSION: Long-term survivors of metastatic colorectal cancer who have undergone liver surgery have excellent global quality of life, high levels of function and few symptoms.

Feasibility RCT of definitive chemoradiotherapy or chemotherapy and surgery for oesophageal squamous cell cancer.

BACKGROUND: The optimal treatment for localised oesophageal squamous cell carcinoma (SCC) is uncertain. We assessed the feasibility of an RCT comparing neoadjuvant treatment and surgery with definitive chemoradiotherapy. METHODS: A feasibility RCT in three centres examined incident patients and reasons for ineligibility using multi-disciplinary team meeting records. Eligible patients were offered participation in the RCT with integrated qualitative research involving audio-recorded recruitment appointments and interviews with patients to inform recruitment training for staff. RESULTS: Of 375 patients with oesophageal SCC, 42 (11.2%) were eligible. Reasons for eligibility varied between centres, with significantly differing proportions of patients excluded because of total tumour length (P=0.002). Analyses of audio-recordings and patient interviews showed that recruiters had challenges articulating the trial design in simple terms, balancing treatment arms and explaining the need for randomisation. Before analyses of the qualitative data and recruiter training no patients were randomised. Following training in one centre 5 of 16 eligible patients were randomised. CONCLUSIONS: An RCT of surgical vs non-surgical treatment for SCC of the oesophagus is not feasible in the UK alone because of the low number of incident eligible patients. A trial comparing diverse treatment approaches may be possible with investment to support the recruitment process.

A systematic review of outcome reporting in colorectal cancer surgery.

AIM: Evaluation of surgery for colorectal cancer (CRC) is necessary to inform clinical decision-making and healthcare policy. The standards of outcome reporting after CRC surgery have not previously been considered. METHOD: Systematic literature searches identified randomized and nonrandomized prospective studies reporting clinical outcomes of CRC surgery. Outcomes were listed verbatim, categorized into broad groups (outcome domains) and examined for a definition (an appropriate textual explanation or a supporting citation). Outcome reporting was considered inconsistent if results of the outcome specified in the methods were not reported. Outcome reporting was compared between randomized and nonrandomized studies. RESULTS: Of 5644 abstracts, 194 articles (34 randomized and 160 nonrandomized studies) were included reporting 766 different clinical outcomes, categorized into seven domains. A mean of 14 ± 8 individual outcomes were reported per study. 'Anastomotic leak', 'overall survival' and 'wound infection' were the three most frequently reported outcomes in 72, 60 and 44 (37.1%, 30.9% and 22.7%) studies, respectively, and no single outcome was reported in every publication. Outcome definitions were significantly more often provided in randomized studies than in nonrandomized studies (19.0% vs 14.9%, P = 0.015). One-hundred and twenty-seven (65.5%) papers reported results of all outcomes specified in the methods (randomized studies, n = 21, 61.5%; nonrandomized studies, n = 106, 66.2%; P = 0.617). CONCLUSION: Outcome reporting in CRC surgery lacks consistency and method. Improved standards of outcome measurement are recommended to permit data synthesis and transparent cross-study comparisons.

What surgeons should tell patients with oesophago-gastric cancer: a cross sectional study of information needs.

BACKGROUND: Evidence shows that patients with cancer have many information needs, but specific requirements of patients undergoing surgery for oesophago-gastric (OG) cancer have not been well explored. This study surveyed information needs of patients with OG cancer and explored associations between patient characteristics and information needs. PATIENTS: A validated questionnaire assessing the importance of information about i) the nature, process and prognosis of the cancer, ii) tests, iii) treatments, and iv) physical and psychosocial outcomes (quality of life information) was completed by patients before and after OG cancer treatment. Items responses were transformed to a 0-100 score and linear regression explored associations between clinical and socio-demographic patient characteristics and patient information needs. RESULTS: Questionnaires from 136 respondents were received (response rate 60%, 25% pre-operative, 77% men, mean age 66). Most types of information were rated as important, with information about prognosis and quality of life issues being scored as highly important by over 112 (82%) patients. Linear regression showed that women rated information relating to treatment and psychosocial effects as more important than men (p < 0.038), but no other associations were identified. CONCLUSIONS: Most patients with OG cancer want detailed information, especially information about prognosis and quality of life. It is recommended that surgeons provide this for patients alongside information that the surgeon considers important.

Optimising methods for communicating survival data to patients undergoing cancer surgery.

BACKGROUND: Patients undergoing cancer surgery require outcome data to inform decisions, but communication of numerical risk is difficult. This study assessed patient understanding of survival data presented in different formats. METHODS: Semi-structured interviews in which patients interpreted four presentation formats of survival data (three graphical and one narrative) were audio-recorded. The interviewer and a blinded observer (listening to the audio-recordings) scored patients' understanding of each format. Logistic regression examined associations between understanding and clinical and socio-demographic details. RESULTS: Seventy participants with colorectal cancer were interviewed and 67 [95.7%, 95% confidence intervals (CIs) 90.9-100%] correctly interpreted a simplified Kaplan-Meier survival curve. A high proportion accurately understood data presented as a bar chart or pictograph (94.3%, 95% CIs 88.7-99.9% and 92.9%, 95% CIs 86.7-99.0% respectively). Standard narrative alone was least well understood (n = 53, 75.7%, 95% CIs 65.4-86.0%). Multivariable analyses demonstrated that older and female patients had poorer overall understanding (OR 0.93 per year, 95% CIs 0.87-0.98, p = 0.01 and OR 0.24, 95% CIs 0.07-0.86, p = 0.03). CONCLUSION: Patient understanding of survival data was higher when presented with graphs compared to narrative alone. Further work examining understanding in the clinical context and before surgery is recommended before this can be used routinely.

Mortality at ages 50-59 and deprivation at early and late stages of the life course in Wales.

BACKGROUND: Most previous studies have examined the association between mortality and deprivation at only one point in time. However, risk accumulates over the life course. The design of the study was ecological. Its aims were to explain inequalities in total and cause-specific mortality between geographical areas in relation to the lifestyle and health behaviours of the resident populations and the area levels of deprivation in 1981 and in 1921-40. METHODS: Data on health behaviour from the 1985 Heartbeat Wales Community Survey were evaluated in light of Welsh mortality rates for the period 1981-99, 1981 census data on socioeconomic position and the infant mortality rates in 1921-40. Negative binomial models were carried out to investigate the district-level association of mortality with deprivation (infant mortality in 1921-40, Carstairs score in 1981, combined index of deprivation) independently from the personal habits and characteristics of the resident population. RESULTS: There was an increased risk of death in deprived areas compared with more wealthy ones. Both infant mortality (a proxy of material deprivation during the time in which the 50-59-year-old individuals were born or were children) and Carstairs scores (a proxy of deprivation during adulthood) were strongly associated with recent mortality. Deprivation had stronger effects in women than in men, the only exception being the effects of later life deprivation on lung cancer. CONCLUSIONS: Area characteristics at different points of time may help to explain geographical inequality in mortality.

WITHDRAWN: Non-aspirin, non-steroidal anti-inflammatory drugs for treating osteoarthritis of the knee.

BACKGROUND: Osteoarthritis(OA) is the most common rheumatic disease. Simple analgesics are now accepted as the appropriate first line pharmacological treatment of uncomplicated OA. Non-aspirin NSAIDs are licensed for the relief of pain and inflammation arising from rheumatic disease. OBJECTIVES: To determine whether there is a difference in the relative efficacy of individual non-steroidal anti-inflammatory drugs (NSAIDs) when used in the management of osteoarthritis (OA) of the knee. SEARCH STRATEGY: We searched Medline (1966-1995) and Bids Embase (Jan-Dec, 1980-1995). The searches were limited to publications in the English language, and were last performed in November 1996. We used modified Cochrane Collaboration search strategy to identify all randomised controlled trials. The MeSH heading "osteoarthritis" was combined with the generic names of the 17 non-aspirin NSAIDs licensed in the UK for the management of OA in general practice. The search of Embase used the term "osteoarthritis" if present in the abstract, title or keywords, and was combined with the generic names of the 17 non-aspirin NSAIDs, only if they were mentioned in the title, abstract or keywords. SELECTION CRITERIA: All double blind, randomised controlled trials, in the English language, comparing the efficacy of two non-aspirin NSAIDs in the management of osteoarthritis of the knee, were selected. Only trials with subjects aged 16 years and over, with clinical and/or radiological confirmation of the diagnosis of OA knee were included. Studies which compared one "trial" NSAID with one "reference" NSAID were included provided they were non-aspirin NSAIDs available in the UK and were licensed for the treatment of OA by general practitioners. Trials which were placebo-controlled and which also involved the comparison of two NSAIDs were also included. DATA COLLECTION AND ANALYSIS: The methodological design of each study was scored according to a pre-determined system. The three main outcome measures of pain, physical function and patient global assessment were chosen based on the core set agreed upon by OMERACT (Outcome Measures in Rheumatology Clinical Trials). These were used to determine the power of each trial. The equivalency of NSAID doses was calculated using the percentage of the recommended maximum daily dose. Sample size estimates for the detection of clinically relevant changes in outcome measures used in the assessment of OA knee were used for power calculations. These calculations were performed to determine whether the trials were of a sufficient size to detect clinically relevant differences which were statistically significant. The calculations incorporate estimates of standard deviation, and minimum, median and maximum differences (delta) between drugs which are deemed to be clinically important. The number of "withdrawals due to lack of efficacy" was also selected as an outcome measure for this review. The Peto odds ratio and 95% confidence intervals were calculated where possible. The results of studies which compared the same trial and reference NSAIDs were combined where possible. MAIN RESULTS: Of the 1151 trials identified by the search strategy, 22 involved knee osteoarthritis only. Sixteen of these trials fulfilled the inclusion criteria and were entered in the review. Eight NSAIDs were represented in these trials. Etodolac was represented in 11 trials. The reference NSAID in these trials was piroxicam (n=3), naproxen(n=3), diclofenac (n=3), indomethacin (n=1), and, nabumetone (n=1). The reported methodological design of the trials was poor, with a median score of 3 (out of a maximum of 8). The results of the trials comparing the same trial and reference NSAIDs were pooled for the outcome "withdrawal due to lack of efficacy". For the comparison, etodolac versus piroxicam, the odds ratio favoured etodolac i.e. patients receiving etodolac were less likely to withdraw due to lack of efficacy. The dose of etodolac used in each of these three studies, however, was greater than the corresponding dose of piroxicam (based on percentage maximum daily dose). The significance of these results is therefore questionable. For the comparisons etodolac versus diclofenac, and etodolac versus naproxen, there were no clear differences between treatments. In one study [Bellamy 1993], a statistically significant difference was detected between treatments with regard to withdrawals due to lack of efficacy. In this trial, which compared equivalent NSAID doses, diclofenac was the favoured NSAID compared to tenoxicam(p=0.04). Two studies showed a statistical difference in patient global assessment of condition, which favoured the trial NSAID. In both cases the trial NSAID was etodolac, used in doses approximately 25-44% greater than the reference NSAID. Two studies showed a statistically significant difference in pain relief between NSAIDs. The trial NSAID in both cases was again etodolac but the doses exceeded those of the reference NSAIDs. AUTHORS' CONCLUSIONS: In spite of the large number of publications in this area, there are few randomized controlled trials. Furthermore, most trials comparing two or more NSAIDs suffer from substantial design errors. From the results of this review it is concluded that no substantial evidence is available related to efficacy, to distinguish between equivalent recommended doses of NSAIDs. Had studies employed appropriate doses of comparator drug, most would have been sufficiently powerful to detect clinically important differences in efficacy. As differences in efficacy between NSAIDs have not been recorded, the selection of an NSAID for prescription for OA knee should be based upon relative safety, patient acceptability and cost.

Development and psychometric evaluation of the ICIQ Vaginal Symptoms Questionnaire: the ICIQ-VS.

OBJECTIVES: To develop and validate a self-completion questionnaire for comprehensive assessment of the severity and impact of vaginal symptoms and related sexual matters, particularly those attributed to pelvic organ prolapse. To provide an instrument that can characterise the severity of these symptoms, measure their impact and evaluate treatment outcome. DESIGN: Prospective development of the content of the questionnaire and testing of its psychometric properties including validity. SETTING: Two hospital-based urogynaecology clinics and one community general practice in the South of England. POPULATION: One hundred and forty-one urogynaecology clinic attendees with varying degrees of pelvic organ prolapse and 77 randomly selected women registered with a general practice. METHODS: The questionnaire was developed through a literature review, consultation with clinicians and health scientists and structured interviews with patients. Content validity, construct validity, stability, internal consistency and sensitivity to change were examined by comparing the responses from the urogynaecology clinic with responses from the general community. Sensitivity to change was assessed using responses from women undergoing surgical treatment for pelvic organ prolapse before and 3 months after surgery. A final version of the questionnaire was obtained after factor analysis to assist item reduction and refinement of the scoring system. MAIN OUTCOME MEASURES: Content validity, construct validity, stability (test-retest reliability), internal consistency and sensitivity to change. RESULTS: The questionnaire exhibited good validity, reliability and sensitivity to change. Excellent internal consistency was demonstrated for vaginal (Cronbach's alpha 0.79) and sexual (Cronbach's alpha 0.84) symptoms. Reliability was good. The questionnaire was able to identify changes in symptoms following surgical treatment. The final ICIQ-VS questionnaire had 14 items and a simple scoring system. CONCLUSION; The ICIQ-VS self-completion questionnaire meets the need for a robust instrument for assessing a range of vaginal and sexual symptoms, in particular those of pelvic organ prolapse. It will be of use in both routine clinical practice and epidemiological research, particularly when there is a need to assess the severity of these symptoms or the efficacy of treatment.

Feasibility of quality of life assessment in patients with upper gastrointestinal tract cancer.

Quality of life (QOL) is an important outcome after treatment for upper gastrointestinal tract cancer but few studies report good accrual and subsequent attrition is usually high. This study investigated the feasibility of a nurse-led service to obtain longitudinal QOL assessments and explored how clinical and sociodemographic factors influence patients' need for help to complete questionnaires. Fully informed patients were invited into the study. Baseline hospital assessments were scheduled by telephone and thereafter by post unless patients' health indicated the need for a home visit. In all, 128 out of 140 (91%) baseline QOL assessments were performed. Follow-up questionnaire completion was good, with 114 patients (89%) completing all but one of the expected assessments. At baseline, 41 (32%) patients required a lot of help to complete questionnaires. Patients requiring help were more likely to be undergoing palliative treatment than treatment aimed at cure (68 vs 33%; odds ratio 3.48, P<0.01). Patients' with advanced stage cancer of the upper gastrointestinal tract receiving palliative treatment require dedicated staff to ensure good compliance with longitudinal QOL data collection. It is essential to budget for this in clinical trails.

The development and validation of a questionnaire to assess visual symptoms/dysfunction and impact on quality of life in cataract patients: the Visual Symptoms and Quality of life (VSQ) Questionnaire.

The aim of the study was to develop a new questionnaire to assess visual symptoms/dysfunction and impact on vision-specific quality of life for those undergoing second eye cataract extraction. Items for the VSQ questionnaire were devised with reference to existing literature and following consultation with eye care experts (n = 18) and interviews with cataract patients (n = 40). Piloting work conducted with 53 patients indicated that the questionnaire was promising, with a high level of internal consistency, low levels of missing data and indications that it was responsive to surgery. A modified version of the questionnaire was completed by 105 patients having received 'early' surgery and 103 scheduled for routine surgery within a randomised controlled trial evaluating the effectiveness of second eye cataract surgery. Analyses showed that the internal consistency of both the visual symptoms/dysfunction and quality of life areas was high (Cronbach's alpha 0.82 and 0.83, respectively). Highly significant improvements were found for early surgery patients (p < 0.0001), with little change among routine surgery patients. Two final versions of the VSQ questionnaire have been produced for future use in assessing visual symptoms/dysfunction and impact on vision-specific quality of life: a scoreable short form and more detailed and sensitive long form.

Subgroup analyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives.

BACKGROUND: Subgroup analyses are common in randomised controlled trials (RCTs). There are many easily accessible guidelines on the selection and analysis of subgroups but the key messages do not seem to be universally accepted and inappropriate analyses continue to appear in the literature. This has potentially serious implications because erroneous identification of differential subgroup effects may lead to inappropriate provision or withholding of treatment. OBJECTIVES: (1) To quantify the extent to which subgroup analyses may be misleading. (2) To compare the relative merits and weaknesses of the two most common approaches to subgroup analysis: separate (subgroup-specific) analyses of treatment effect and formal statistical tests of interaction. (3) To establish what factors affect the performance of the two approaches. (4) To provide estimates of the increase in sample size required to detect differential subgroup effects. (5) To provide recommendations on the analysis and interpretation of subgroup analyses. METHODS: The performances of subgroup-specific and formal interaction tests were assessed by simulating data with no differential subgroup effects and determining the extent to which the two approaches (incorrectly) identified such an effect, and simulating data with a differential subgroup effect and determining the extent to which the two approaches were able to (correctly) identify it. Initially, data were simulated to represent the 'simplest case' of two equal-sized treatment groups and two equal-sized subgroups. Data were first simulated with no differential subgroup effect and then with a range of types and magnitudes of subgroup effect with the sample size determined by the nominal power (50-95%) for the overall treatment effect. Additional simulations were conducted to explore the individual impact of the sample size, the magnitude of the overall treatment effect, the size and number of treatment groups and subgroups and, in the case of continuous data, the variability of the data. The simulated data covered the types of outcomes most commonly used in RCTs, namely continuous (Gaussian) variables, binary outcomes and survival times. All analyses were carried out using appropriate regression models, and subgroup effects were identified on the basis of statistical significance at the 5% level. RESULTS: While there was some variation for smaller sample sizes, the results for the three types of outcome were very similar for simulations with a total sample size of greater than or equal to 200. With simulated simplest case data with no differential subgroup effects, the formal tests of interaction were significant in 5% of cases as expected, while subgroup-specific tests were less reliable and identified effects in 7-66% of cases depending on whether there was an overall treatment effect. The most common type of subgroup effect identified in this way was where the treatment effect was seen to be significant in one subgroup only. When a simulated differential subgroup effect was included, the results were dependent on the nominal power of the simulated data and the type and magnitude of the subgroup effect. However, the performance of the formal interaction test was generally superior to that of the subgroup-specific analyses, with more differential effects correctly identified. In addition, the subgroup-specific analyses often suggested the wrong type of differential effect. The ability of formal interaction tests to (correctly) identify subgroup effects improved as the size of the interaction increased relative to the overall treatment effect. When the size of the interaction was twice the overall effect or greater, the interaction tests had at least the same power as the overall treatment effect. However, power was considerably reduced for smaller interactions, which are much more likely in practice. The inflation factor required to increase the sample size to enable detection of the interaction with the same power as the overall effect varied with the size of the interaction. For an interaction of the same magnitude as the overall effect, the inflation factor was 4, and this increased dramatically to of greater than or equal to 100 for more subtle interactions of < 20% of the overall effect. Formal interaction tests were generally robust to alterations in the number and size of the treatment and subgroups and, for continuous data, the variance in the treatment groups, with the only exception being a change in the variance in one of the subgroups. In contrast, the performance of the subgroup-specific tests was affected by almost all of these factors with only a change in the number of treatment groups having no impact at all. CONCLUSIONS: While it is generally recognised that subgroup analyses can produce spurious results, the extent of the problem is almost certainly under-estimated. This is particularly true when subgroup-specific analyses are used. In addition, the increase in sample size required to identify differential subgroup effects may be substantial and the commonly used 'rule of four' may not always be sufficient, especially when interactions are relatively subtle, as is often the case. CONCLUSIONS--RECOMMENDATIONS FOR SUBGROUP ANALYSES AND THEIR INTERPRETATION: (1) Subgroup analyses should, as far as possible, be restricted to those proposed before data collection. Any subgroups chosen after this time should be clearly identified. (2) Trials should ideally be powered with subgroup analyses in mind. However, for modest interactions, this may not be feasible. (3) Subgroup-specific analyses are particularly unreliable and are affected by many factors. Subgroup analyses should always be based on formal tests of interaction although even these should be interpreted with caution. (4) The results from any subgroup analyses should not be over-interpreted. Unless there is strong supporting evidence, they are best viewed as a hypothesis-generation exercise. In particular, one should be wary of evidence suggesting that treatment is effective in one subgroup only. (5) Any apparent lack of differential effect should be regarded with caution unless the study was specifically powered with interactions in mind. CONCLUSIONS--RECOMMENDATIONS FOR RESEARCH: (1) The implications of considering confidence intervals rather than p-values could be considered. (2) The same approach as in this study could be applied to contexts other than RCTs, such as observational studies and meta-analyses. (3) The scenarios used in this study could be examined more comprehensively using other statistical methods, incorporating clustering effects, considering other types of outcome variable and using other approaches, such as Bootstrapping or Bayesian methods.

Transurethral prostatic resection or laser therapy for men with acute urinary retention: the ClasP randomized trial.

PURPOSE: Transurethral resection of the prostate is the standard operation for acute urinary retention, although laser prostatectomy is reportedly effective and safe. The ClasP (conservative management, laser, transurethral resection of the prostate) study compared transurethral prostatic resection and noncontact neodymium (Nd):YAG visual laser assisted prostatectomy for treatment of acute urinary retention. MATERIALS AND METHODS: This study was a multicenter randomized controlled trial, analyses were by intention to treat and followup was at 7.5 months after randomization. Primary outcomes were treatment failure, and included International Prostate Symptom Score, International Prostate Symptom Score quality of life score, residual urine and flow rate. Secondary outcomes included complications, and duration of catheterization and hospitalization. RESULTS: A total of 148 men were randomized to transurethral prostatic resection (74) and laser (74). There were fewer treatment failures after prostatic resection (p = 0.008) and fewer men after resection required secondary surgery for poor results (1 versus 7, p = 0.029). Maximum flow rates after transurethral prostatic resection were better than after laser (mean difference 4.4 ml. per second). Comparison of symptom and quality of life scores demonstrated that any clinically significant advantage for laser could be ruled out. Patients stayed a mean of 2 extra days in the hospital after resection. The duration of catheterization was greater after laser but significantly fewer major treatment complications were found with laser therapy. CONCLUSIONS: Transurethral prostatic resection was more effective, resulted in fewer failures than laser treatment and remains the procedure of choice for men with acute urinary retention.

The prognostic value of quality of life scores during treatment for oesophageal cancer.

BACKGROUND: Quality of life (QL) data are useful to evaluate the effectiveness of treatment. Accumulating evidence suggests that QL data may predict survival. AIMS: In this study we investigated if baseline QL scores and changes in QL scores before and after intervention are prognostic for patients with oesophageal cancer. PATIENTS: Between 1993 and 1995, 92 consecutive new patients with oesophageal cancer were studied; 89 were followed until death or the end of the study period (survival of seven patients was censored in May 1999). METHODS: All patients completed the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire (EORTC QLQ-C30) and the dysphagia scale of the oesophageal module (EORTC QLQ-OES24) before treatment and at regular intervals throughout the study. Cox's proportional hazards models assessed the impact of baseline QL variables and changes in QL scores on survival. RESULTS: Cox's proportional hazards models, adjusting for associations between QL scores, age, and TNM stage, found that physical function at baseline was significantly associated with survival (p=0.002). An increase in physical function score of 10 points corresponded to a 12% reduction in the likelihood of death at any given time (95% confidence intervals 4--18%). Further exploratory multivariable analyses suggested that improvement in emotional function six months after treatment was significantly related to longer survival (p<0.0001). CONCLUSIONS: These data provide evidence to support a relationship between patient rated scores of QL and survival. Further understanding of the associations between QL and clinical variables is needed.

Scoring the short form ICSmaleSF questionnaire. International Continence Society.

PURPOSE: The International Continence Society (ICS) ICSmale questionnaire was devised to provide a thorough evaluation of the occurrence and bothersomeness of lower urinary tract symptoms and their impact on the lives of men with benign prostatic disease. This report completes the developmental work on the questionnaire, producing the concise short form instrument, ICSmaleSF, with a valid, reliable and scientifically justified scoring system. MATERIALS AND METHODS: Two data sets were used. The short form version of the questionnaire was devised and initially evaluated using data on men with uncomplicated lower urinary tract symptoms who were involved in the CLasP randomized controlled trial comparing laser therapy with transurethral prostatic resection and conservative management or monitoring without active intervention. External validation of the scoring system was undertaken using data from phase II of the ICS benign prostatic hyperplasia (BPH) study, an observational study of outcome in men with lower urinary tract symptoms related to benign prostatic enlargement. All patients completed the developmental version of the ICSmale questionnaire. Parallel analysis on the CLasP data set identified items that were responsive to change or highly problematic, allowing other redundant and overlapping items to be eliminated. Factor analysis and Cronbach's alpha coefficients were used to examine the clustering of items. Regression models were used to investigate the validity of followup scores within and across treatment groups in the CLasP and ICS/BPH studies. RESULTS: The questionnaire, which originally comprised 22 items, was shortened to 11 items in the 2 distinct factors of voiding (ICSmaleVS) and incontinence (ICSmaleIS) symptoms. Cronbach's alpha coefficients were high at 0.76 for ICSmaleVS and 0.78 for ICSmaleIS. A simple additive score was calculated by adding the 5 items in ICSmaleVS and 6 in ICSmaleIS. ICSmaleVS and ICSmaleIS detected expected improvement in the laser therapy and transurethral prostatic resection groups, and stability in the conservative management group within CLasP. Similarly each subscore but particularly ICSmaleVS was sensitive to differences in the outcome of the range of treatments in the ICS/BPH study. While frequency and nocturia were highly problematic and sensitive to change individually, they did not load into the other main factors or correlate with each other. It is suggested that these symptoms should be evaluated separately with the additional inclusion of a single item measure of the impact of lower urinary tract symptoms on daily life. CONCLUSIONS: The ICSmaleSF represents a comprehensive, concise, valid and reliable instrument for evaluating men with lower urinary tract symptoms. Unlike other questionnaires in the field it contains subscores for the domains of voiding and incontinent symptoms as well as the separate consideration of frequency, nocturia and impact on daily life. We hope that it will become the tool of choice for the comprehensive evaluation of treatment of men with lower urinary tract symptoms associated with benign prostatic disease.

A prospective randomized trial comparing transurethral resection of the prostate and laser therapy in men with chronic urinary retention: The CLasP study.

PURPOSE: We assessed the effectiveness of laser therapy versus transurethral prostatic resection in men with symptomatic chronic urinary retention secondary to benign prostatic enlargement. MATERIALS AND METHODS: This trial was multicenter, pragmatic and randomized. Analysis was done by intent to treat. Laser therapy involved neodymium:YAG noncontact visual prostate ablation, while transurethral prostatic resection was performed by standard electroresection. Patients were included in our study if they reported moderate to severe lower urinary tract symptoms with an International Prostate Symptom Score (I-PSS) of 8 or more, benign prostatic enlargement and a persistent post-void residual urine volume of more than 300 ml. Followup was 7.5 months. Primary outcome measures included the I-PSS, I-PSS quality of life score, maximum urinary flow and post-void residual urine volume. Secondary outcome measures included treatment failure, complications, hospital stay and catheterization time. RESULTS: A total of 82 patients agreed to be randomized to receive laser therapy (38) or transurethral prostatic resection (44). There were significant improvements in all primary outcomes in each group from randomization to followup. Transurethral prostatic resection was significantly better than laser therapy for I-PSS and maximum urinary flow values (p = 0.035 and 0.029, respectively) but there were no differences in post-void residual urine volume and I-PSS quality of life score between the groups. We noted significantly more treatment failures with laser therapy than resection (8 versus 0, p = 0.0014), although only 3 patients required resection after laser therapy because of persistent symptoms. In addition, hospital stay after resection was 2-fold that after laser therapy (ratio of geometric means 2.01, 95% confidence interval 1.54 to 2.61, p <0.0001). However, time to catheter removal was 9 times longer in the laser therapy group (p <0. 0001). Complication rates were significantly higher for transurethral prostatic resection (chi-square 5.05, 1 df, p = 0.025). CONCLUSIONS: Transurethral prostatic resection is more effective than laser ablation in men with chronic urinary retention in terms of symptom score, maximum urinary flow and failure. However, men who underwent resection had significantly more treatment complications and were hospitalized longer than those who received laser therapy. This finding implies that laser ablation therapy may have a role in patients at higher risk who are willing to accept a lower level of effectiveness in exchange for decreased complication rates and hospital stay.

A randomized trial comparing transurethral resection of the prostate, laser therapy and conservative treatment of men with symptoms associated with benign prostatic enlargement: The CLasP study.

PURPOSE: We evaluated the effectiveness of a new technology (noncontact laser therapy) versus that of standard surgery (transurethral prostatic resection) and conservative management for lower urinary tract symptoms associated with benign prostatic enlargement. MATERIALS AND METHODS: Men with uncomplicated lower urinary tract symptoms, that is no acute or chronic urinary retention, were randomized to receive laser therapy with a noncontact, side firing neodymium:YAG probe, standard transurethral prostatic resection or conservative management, including monitoring without active intervention, in a large multicenter pragmatic randomized controlled trial called the CLasP study. Primary outcomes were International Prostate Symptom Score (I-PSS), maximum urinary flow rate, a composite measure of success based on I-PSS and maximum urinary flow rate categories, I-PSS quality of life score and post-void residual urine volume. Secondary outcomes included treatment failure, hospital stay and major complications. Followup was 7.5 months after randomization. Intent to treat analysis was done using analysis of covariance, proportional odds models and the Newman-Keuls multiple comparisons procedure. RESULTS: Of symptomatic patients 117, 117 and 106 were randomized to receive laser therapy, transurethral prostatic resection and conservative management, respectively. Baseline characteristics were similar. All primary outcomes indicated that transurethral prostatic resection and laser therapy were superior to conservative management, and resection was superior to laser therapy. As measured by combined improved symptoms and maximum urinary flow, a successful outcome was achieved in 81%, 67% and 15% of men who underwent transurethral prostatic resection, laser therapy and conservative management, respectively. Hospital stay was significantly shorter and complications fewer for laser therapy than for resection but catheters were in place significantly longer. Men treated conservatively did not have deterioration or treatment failure. CONCLUSIONS: Laser therapy and transurethral prostatic resection are effective for decreasing lower urinary tract symptoms and post-void residual urine volume as well as improving quality of life and maximum urinary flow in the short term in men presenting with moderate to severe symptoms. Transurethral prostatic resection is superior to laser therapy in terms of effectiveness but some patients may elect laser therapy due to the shorter hospital stay and lower risk of complications. Conservative management may be acceptable and safe in men with lower urinary tract symptoms since we observed no marked deterioration in the short term.

Non-aspirin, non-steroidal anti-inflammatory drugs for osteoarthritis of the knee.

OBJECTIVES: To determine whether there is a difference in the relative efficacy of individual non-steroidal anti-inflammatory drugs (NSAIDs) when used in the management of osteoarthritis (OA) of the knee. SEARCH STRATEGY: We searched Medline (1966-1995) and Bids Embase (Jan-Dec, 1980-1995). The searches were limited to publications in the English language, and were last perfomed in November 1996. We used modified Cochrane Collaboration search strategy to identify all randomised controlled trials. The MeSH heading osteoarthritis was combined with the generic names of the 17 non-aspirin NSAIDs licensed in the UK for the management of OA in general practice. The search of Embase used the term "osteoarthritis" if present in the abstract, title or keywords, and was combined with the generic names of the 17 non-aspirin NSAIDs, only if they were mentioned in the title, abstract or keywords. SELECTION CRITERIA: All double blind, randomised controlled trials, in the English language, comparing the efficacy of two non-aspirin NSAIDs in the management of osteoarthritis of the knee, were selected. Only trials with subjects aged 16 years and over, with clinical and/or radiological confirmation of the diagnosis of OA knee were included. Studies which compared one "trial" NSAID with one "reference" NSAID were included provided they were non-aspirin NSAIDs available in the UK and were licensed for the treatment of OA by general practitioners. Trials which were placebo-controlled and which also involved the comparison of two NSAIDs were also included. DATA COLLECTION AND ANALYSIS: The methodological design of each study was scored according to a pre-determined system. The three main outcome measures of pain, physical function and patient global assessment were chosen based on the core set agreed upon by OMERACT (Outcome Measures in Rheumatology Clinical Trials). These were used to determine the power of each trial. The equivalency of NSAID doses was calculated using the percentage of the recommended maximum daily dose. Sample size estimates for the detection of clinically relevant changes in outcome measures used in the assessment of OA knee were used for power calculations. These calculations were performed to determine whether the trials were of a sufficient size to detect clinically relevant differences which were statistically significant. The calculations incorporate estimates of standard deviation, and minimum, median and maximum differences (delta) between drugs which are deemed to be clinically important. The number of "withdrawals due to lack of efficacy" was also selected as an outcome measure for this review. The Peto odds ratio and 95% confidence intervals were calculated where possible. The results of studies which compared the same trial and reference NSAIDs were combined where possible. MAIN RESULTS: Of the 1151 trials identified by the search strategy, 22 involved knee osteoarthritis only. Sixteen of these trials fulfilled the inclusion criteria and were entered in the review. Eight NSAIDs were represented in these trials. Etodolac was represented in 11 trials. The reference NSAID in these trials was piroxicam (n=3), naproxen(n=3), diclofenac (n=3), indomethacin (n=1), and, nabumetone (n=1). The reported methodological design of the trials was poor, with a median score of 3 (out of a maximum of 8). The results of the trials comparing the same trial and reference NSAIDs were pooled for the outcome "withdrawal due to lack of efficacy". For the comparison, etodolac vesus piroxicam, the odds ratio favoured etodolac i.e. patients receiving etodolac were less likely to withdraw due to lack of efficacy. The dose of etodolac used in each of these three studies, however, was greater than the corresponding dose of piroxicam (based on percentage maximum daily dose). The significance of these results is therefore questionable. For the comparisons etodolac versus diclofenac, and etodolac versus naproxen, there were no clear differences betw