Pharmaceutical policies: effects of cap and co-payment on rational drug use.

BACKGROUND: Growing expenditures on prescription drugs represent a major challenge to many health systems. Cap and co-payment (direct cost-share) policies are intended as an incentive to deter unnecessary or marginal utilisation, and to reduce third-party payer expenditures by shifting parts of the financial burden from the insurer to patients, thus increasing their financial responsibility for prescription drugs. Direct patient drug payment policies include caps (maximum number of prescriptions or drugs that are reimbursed), fixed co-payments (patients pay a fixed amount per prescription or drug), coinsurance (patients pay a percent of the price), ceilings (patients pay the full price or part of the cost up to a ceiling, after which drugs are free or available at reduced cost), and tier co-payments (differential co-payments usually assigned to generic and brand drugs). OBJECTIVES: To determine the effects of cap and co-payment (cost-sharing) policies on drug use, healthcare utilisation, health outcomes and costs (expenditures). SEARCH STRATEGY: We searched the following databases and web sites: Effective Practice and Organisation of Care Group Register (date of last search: 6 September 07), Cochrane Central Register of Controlled Trials (27 August 07), MEDLINE (29 August 07), EMBASE (29 August 07), NHS EED (27 August 07), ISI Web of Science (09 January 07), CSA Worldwide Political Science Abstracts (21 October 03), EconLit (23 October 03), SIGLE (12 November 03), INRUD (21 November 03), PAIS International (23 March 04), International Political Science Abstracts (09 January 04), PubMed (25 February 04), NTIS (03 March 04), IPA (22 April 04), OECD Publications & Documents (30 August 05), SourceOECD (30 August 05), World Bank Documents & Reports (30 August 05), World Bank e-Library (04 May 05), JOLIS (22 February 06), Global Jolis (22 February 06), WHOLIS(22 February 06), WHO web site browsed (25 August 05). SELECTION CRITERIA: We defined policies in this review as laws, rules, or financial or administrative orders made by governments, non-government organisations or private insurers. We included randomised controlled trials, non-randomised controlled trials, interrupted time series analyses, repeated measures studies and controlled before-after studies of cap or co-payment policies for a large jurisdiction or system of care. To be included, a study had to include an objective measure of at least one of the following outcomes: drug use, healthcare utilisation, health outcomes or costs (expenditures). DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed study limitations. We undertook quantitative analysis of time series data for studies with sufficient data. MAIN RESULTS: We included 30 evaluations (in 21 studies). Of these, 11 evaluated fixed co-payment, six evaluated coinsurance with a ceiling, four evaluated caps, three evaluated fixed co-payment with a ceiling, three evaluated tier co-payment, one evaluated ceiling, one evaluated fixed co-payment and coinsurance with a ceiling, and one evaluated a fixed co-payment with a cap. Most of the included evaluations were observational studies and the quality of the evidence was found to be generally low to moderate. Introducing or increasing direct co-payments reduced drug use and saved plan drug expenditures across studies. Patients responded through drug discontinuation or by cost-sharing. Investigators found reductions for life-sustaining drugs or drugs that are important in treating chronic conditions as well as other drugs. Few studies reported on the effects on health and healthcare utilisation. One study found adverse effects on health through increased healthcare utilisation when a cap was introduced in a vulnerable population. No statistically significant change in use of healthcare services was found in other studies when a cap was introduced on a drug considered over-prescribed in a vulnerable population, or following a shift from a two-tier to a three-tier system with increased co-payments for tier-1 drugs in a general population. AUTHORS' CONCLUSIONS: We found a diversity of cap and co-payment policies. Poor reporting of the intensity of interventions and differences in setting, populations and interventions made it difficult to make comparisons across studies. Cap and co-payment polices can reduce drug use and save plan drug expenditures. However, although insufficient data on health outcomes were available, substantial reductions in the use of life-sustaining drugs or drugs that are important in treating chronic conditions may have adverse effects on health, and as a result increase the use of healthcare services and overall expenditures. Direct payments are less likely to cause harm if only non-essential drugs are included or exemptions are built in to ensure that patients receive needed medical care.

Randomisation to protect against selection bias in healthcare trials.

BACKGROUND: Randomised trials use the play of chance to assign participants to comparison groups. The unpredictability of the process, if not subverted, should prevent systematic differences between comparison groups (selection bias), provided that a sufficient number of people are randomised. OBJECTIVES: To assess the effects of randomisation and concealment of allocation on the results of healthcare trials. SEARCH STRATEGY: We searched the Cochrane Methodology Register, MEDLINE, SciSearch, reference lists up to August 2000 and used personal communication. SELECTION CRITERIA: Cohorts of trials, systematic reviews or meta-analyses of healthcare interventions that compared outcomes or prognostic factors for one of the following comparisons: randomised versus non-randomised trials, randomised trials with adequately versus inadequately concealed allocation, or high versus low quality trials where selection bias could not be separated from other sources of bias. DATA COLLECTION AND ANALYSIS: One of us went through all of the citations in the Cochrane Methodology Register and accumulated reference lists. Studies that appeared to meet the inclusion criteria were retrieved and assessed independently by two of the reviewers. The methodological quality of included studies was appraised and information extracted by one of us and checked by a second. Tabular summaries of the results were prepared for each comparison and the results across studies were assessed qualitatively to identify common trends or discrepancies. MAIN RESULTS: We identified 32 studies including over 3000 trials. Twenty-two studies compared randomised versus non-randomised trials, three compared adequately versus inadequately concealed allocation, and nine compared high versus low quality trials (some studies included more than one comparison). Five studies were of high methodological quality. In 15 of the 22 studies that compared randomised and non-randomised trials of the same intervention, important differences were found in the estimates of effect. Some of these differences were due to a poorer prognosis in the control groups in the non-randomised trials. The results of the other seven studies that compared randomised and non-randomised trials across different interventions are less clear. Comparisons of adequately and inadequately concealed allocation in randomised trials of the same intervention provided high quality evidence that concealment can be crucial in achieving similar treatment groups and, therefore, unbiased estimates of treatment effects. Studies with inadequate concealment tended to overestimate treatment effects. Comparisons of high and low quality trials of the same intervention have found important differences in estimates of effect, but it is not possible to determine the extent to which these differences can be attributed to randomisation or concealment of allocation. Omitting comparisons between randomised trials and non-randomised trials using historical controls did not substantially alter the results or conclusions of our review. AUTHORS' CONCLUSIONS: On average, non-randomised trials and randomised trials with inadequate concealment of allocation tend to result in larger estimates of effect than randomised trials with adequately concealed allocation. However, it is not generally possible to predict the magnitude, or even the direction, of possible selection biases and consequent distortions of treatment effects.

Outcomes of patients who participate in randomised controlled trials compared to similar patients receiving similar interventions who do not participate.

BACKGROUND: Some people believe that patients who take part in randomised controlled trials (RCTs) face risks that they would not face if they opted for non-trial treatment. Others think that trial participation is beneficial and the best way to ensure access to the most up to date physicians and treatments. OBJECTIVES: To assess the effects of patient participation in RCTs ('trial effects') independent both of the effects of the clinical treatments being compared ('treatment effects') and any differences between patients who participated in RCTs and those who did not. SEARCH STRATEGY: In May 2001, we searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, The Cochrane Methodology Register, SciSearch and PsycINFO for potentially relevant studies. Our search yielded over 10,000 references. In addition, we reviewed the reference lists of relevant articles and wrote to over 250 investigators to try to obtain further information. SELECTION CRITERIA: Randomised studies and cohort studies with data on clinical outcomes of RCT participants and similar patients who received similar treatment outside of RCTs. DATA COLLECTION AND ANALYSIS: At least two reviewers independently assessed studies for inclusion, assessed study quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: We included five randomised studies (yielding 6 comparisons) and 50 non-randomised cohort studies (85 comparisons), with 31,140 patients treated in RCTs and 20,380 patients treated outside RCTs. In the randomised studies, patients were invited to participate in an RCT or not; these comparisons provided limited information because of small sample sizes (a total of 412 patients) and the nature of the questions they addressed. There was statistically significant heterogeneity (P < 0.002, I(2) = 36.2%) among the 73 dichotomous outcome comparisons; none of the potential explanatory factors we investigated helped to explain this heterogeneity. No statistically significant differences were found for 63 of the 73 comparisons. Eight comparisons reported statistically significant better outcomes for patients treated within RCTs, and two comparisons reported statistically significant worse outcomes for patients treated within RCTs. There were no statistically significant differences in heterogeneity (P = 0.53, I(2) = 0%) or in outcomes (SMD 0.01, 95% CI -0.10 to 0.12) of patients treated within and outside RCTs in the 18 comparisons which had used continuous outcomes. AUTHORS' CONCLUSIONS: This review indicates that participation in RCTs is not associated with greater risks than receiving the same treatment outside RCTs. These results challenge the assertion that the results of RCTs are not applicable to usual practice.

WITHDRAWN: Audit and feedback versus alternative strategies: effects on professional practice and health care outcomes.

BACKGROUND: Audit and feedback has been identified as having the potential to change the practice of health care professionals. OBJECTIVES: To assess the effects of audit and feedback compared with other interventions in changing health professional practice and to assess whether the effectiveness of audit and feedback can be improved by modifying how it is done. SEARCH STRATEGY: We searched MEDLINE up to June 1997, the Research and Development Resource Base in Continuing Medical Education, and reference lists of related systematic reviews and articles. SELECTION CRITERIA: Randomised trials of audit and feedback (defined as any summary of clinical performance of health care over a specified period of time) compared with other interventions. The participants were health care providers responsible for patient care. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Twelve studies were included involving more than 2194 physicians. Seven trials with direct comparisons were included. The targeted behaviours were the management of low haemoglobin, the delivery of preventive care services (two studies), the management of high cholesterol, the performance of cervical smears, and the ordering of diagnostic tests (two studies). From the results of four trials, there is little evidence of a measurable effect of adding a complementary intervention such as a local consensus process to audit and feedback compared to audit and feedback alone. Two of three trials that compared audit and feedback to reminders reported that reminders were more effective in improving the delivery of some preventive services. AUTHORS' CONCLUSIONS: It is not possible to recommend a complementary intervention to enhance the effectiveness of audit and feedback. Reminders might be more effective than audit and feedback to improve the delivery of some preventive services but the results are not striking. Few trials have investigated the effect of varying different characteristics of the audit and feedback process. Consideration should be given to testing the effects of modifying important characteristics such as the content, source, timing, recipient and format.

Pharmaceutical policies: effects of financial incentives for prescribers.

BACKGROUND: Pharmaceuticals, while central to medical therapy, pose a significant burden to health care budgets. Therefore regulations to control prescribing costs and improve quality of care are implemented increasingly. These include the use of financial incentives for prescribers, namely increased financial accountability using budgets and performance based payments. OBJECTIVES: To determine the effects on drug use, healthcare utilisation, health outcomes and costs (expenditures) of policies, that intend to affect prescribers by means of financial incentives. SEARCH STRATEGY: We searched the following databases and web sites: Effective Practice and Organisation of Care Group Register (August 2003), Cochrane Central Register of Controlled Trials (October 2003), MEDLINE (October 2005), EMBASE (October 2005), and other databases. SELECTION CRITERIA: Policies were defined as laws, rules, financial and administrative orders made by governments, non-government organisations or private insurers. One of the following outcomes had to be reported: drug use, healthcare utilisation, health outcomes, and costs. The study had to be a randomised or non-randomised controlled trial, interrupted time series analysis, repeated measures study or controlled before-after study evaluating financial incentives for prescribers introduced for a jurisdiction or healthcare system. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study limitations. MAIN RESULTS: Thirteen evaluations of budgetary policies and none of performance based payments met our inclusion criteria. Ten studies evaluated general practice fundholding in the UK, one the Irish Indicative Drug Target Savings Scheme (IDTSS) and two evaluated German drug budgets for physicians in private practice. The interrupted time series analyses had some limitations. All the controlled before-after studies (all from the UK) had serious limitations. Drug expenditure (per item and per patient) and prescribed drug volume decreased with budgets in all three countries. Evidence indicated increased use of generic drugs in the UK and Ireland, but was inconclusive on the use of new and expensive drugs. We found no clear evidence of increased health care utilisation and no studies reporting effects on health. Administration costs were not reported. No studies on the effects of performance-based payments or other policies met our inclusion criteria. AUTHORS' CONCLUSIONS: Based on the evidence in this review from three Western European countries, drug budgets for physicians in private practice can limit drug expenditure by limiting the volume of prescribed drugs, increasing the use of generic drugs or both. Since the majority of studies included were found to have serious limitations, these results should be interpreted with care.

Educational outreach visits: effects on professional practice and health care outcomes.

BACKGROUND: Educational outreach visits (EOVs) have been identified as an intervention that may improve the practice of healthcare professionals. This type of face-to-face visit has been referred to as university-based educational detailing, academic detailing, and educational visiting. OBJECTIVES: To assess the effects of EOVs on health professional practice or patient outcomes. SEARCH STRATEGY: For this update, we searched the Cochrane EPOC register to March 2007. In the original review, we searched multiple bibliographic databases including MEDLINE and CINAHL. SELECTION CRITERIA: Randomised trials of EOVs that reported an objective measure of professional performance or healthcare outcomes. An EOV was defined as a personal visit by a trained person to healthcare professionals in their own settings. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. We used bubble plots and box plots to visually inspect the data. We conducted both quantitative and qualitative analyses. We used meta-regression to examine potential sources of heterogeneity determined a priori. We hypothesised eight factors to explain variation across effect estimates. In our primary visual and statistical analyses, we included only studies with dichotomous outcomes, with baseline data and with low or moderate risk of bias, in which the intervention included an EOV and was compared to no intervention. MAIN RESULTS: We included 69 studies involving more than 15,000 health professionals. Twenty-eight studies (34 comparisons) contributed to the calculation of the median and interquartile range for the main comparison. The median adjusted risk difference (RD) in compliance with desired practice was 5.6% (interquartile range 3.0% to 9.0%). The adjusted RDs were highly consistent for prescribing (median 4.8%, interquartile range 3.0% to 6.5% for 17 comparisons), but varied for other types of professional performance (median 6.0%, interquartile range 3.6% to 16.0% for 17 comparisons). Meta-regression was limited by the large number of potential explanatory factors (eight) with only 31 comparisons, and did not provide any compelling explanations for the observed variation in adjusted RDs. There were 18 comparisons with continuous outcomes, with a median adjusted relative improvement of 21% (interquartile range 11% to 41%). There were eight trials (12 comparisons) in which the intervention included an EOV and was compared to another type of intervention, usually audit and feedback. Interventions that included EOVs appeared to be slightly superior to audit and feedback. Only six studies evaluated different types of visits in head-to-head comparisons. When individual visits were compared to group visits (three trials), the results were mixed. AUTHORS' CONCLUSIONS: EOVs alone or when combined with other interventions have effects on prescribing that are relatively consistent and small, but potentially important. Their effects on other types of professional performance vary from small to modest improvements, and it is not possible from this review to explain that variation.

Audit and feedback: effects on professional practice and health care outcomes.

BACKGROUND: Audit and feedback continues to be widely used as a strategy to improve professional practice. It appears logical that healthcare professionals would be prompted to modify their practice if given feedback that their clinical practice was inconsistent with that of their peers or accepted guidelines. Yet, audit and feedback has not consistently been found to be effective. OBJECTIVES: To assess the effects of audit and feedback on the practice of healthcare professionals and patient outcomes. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group's register and pending file up to January 2004. SELECTION CRITERIA: Randomised trials of audit and feedback (defined as any summary of clinical performance over a specified period of time) that reported objectively measured professional practice in a healthcare setting or healthcare outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. Quantitative (meta-regression), visual and qualitative analyses were undertaken. For each comparison we calculated the risk difference (RD) and risk ratio (RR), adjusted for baseline compliance when possible, for dichotomous outcomes and the percentage and the percent change relative to the control group average after the intervention, adjusted for baseline performance when possible, for continuous outcomes. We investigated the following factors as possible explanations for the variation in the effectiveness of interventions across comparisons: the type of intervention (audit and feedback alone, audit and feedback with educational meetings, or multifaceted interventions that included audit and feedback), the intensity of the audit and feedback, the complexity of the targeted behaviour, the seriousness of the outcome, baseline compliance and study quality. MAIN RESULTS: Thirty new studies were added to this update, and a total of 118 studies are included. In the primary analysis 88 comparisons from 72 studies were included that compared any intervention in which audit and feedback is a component compared to no intervention. For dichotomous outcomes the adjusted risk difference of compliance with desired practice varied from - 0.16 (a 16 % absolute decrease in compliance) to 0.70 (a 70% increase in compliance) (median = 0.05, inter-quartile range = 0.03 to 0.11) and the adjusted risk ratio varied from 0.71 to 18.3 (median = 1.08, inter-quartile range = 0.99 to 1.30). For continuous outcomes the adjusted percent change relative to control varied from -0.10 (a 10 % absolute decrease in compliance) to 0.68 (a 68% increase in compliance) (median = 0.16, inter-quartile range = 0.05 to 0.37). Low baseline compliance with recommended practice and higher intensity of audit and feedback were associated with larger adjusted risk ratios (greater effectiveness) across studies. AUTHORS' CONCLUSIONS: Audit and feedback can be effective in improving professional practice. When it is effective, the effects are generally small to moderate. The relative effectiveness of audit and feedback is likely to be greater when baseline adherence to recommended practice is low and when feedback is delivered more intensively.

Pharmaceutical policies: effects of reference pricing, other pricing, and purchasing policies.

BACKGROUND: Pharmaceuticals can be important for people's health. At the same time drugs are major components of health care costs. Pharmaceutical pricing and purchasing policies are used to determine or affect the prices that are paid for drugs. Examples are price controls, maximum prices, price negotiations, reference pricing, index pricing and volume-based pricing policies. The essence of reference pricing is to establish a maximum level of reimbursement for a group of drugs assumed to be therapeutically equivalent. OBJECTIVES: To determine the effects of pharmaceutical pricing and purchasing policies on drug use, healthcare utilisation, health outcomes and costs (expenditures). SEARCH STRATEGY: We searched the following databases and web sites: Effective Practice and Organisation of Care Group Register (date of last search: 22/08/03), Cochrane Central Register of Controlled Trials (15/10/03), MEDLINE (07/09/05), EMBASE (07/09/05), ISI Web of Science (08/09/05), CSA Worldwide Political Science Abstracts (21/10/03), EconLit (23/10/03), SIGLE (12/11/03), INRUD (21/11/03), PAIS International (23/03/04), International Political Science Abstracts (09/01/04), NHS EED (20/02/04), PubMed (25/02/04), NTIS (03/03/04), IPA (22/04/04), OECD Publications & Documents (30/08/05), SourceOECD (30/08/05), World Bank Documents & Reports (30/08/05), World Bank e-Library (04/05/05), JOLIS (22/08/05), Global Jolis (22/08/05 and 23/08/05), WHOLIS (29/08/05). SELECTION CRITERIA: Policies in this review were defined as laws, rules, financial and administrative orders made by governments, non-government organisations or private insurers. To be included a study had to include an objective measure of at least one of the following outcomes: drug use, healthcare utilisation, health outcomes, and costs (expenditures); the study must be a randomised controlled trial, non-randomised controlled trial, interrupted time series analysis, repeated measures study or controlled before-after study of a pharmaceutical pricing or purchasing policy for a large jurisdiction or system of care. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study limitations. Quantitative analysis of time series data, for studies with sufficient data, and qualitative analyses were undertaken. MAIN RESULTS: We included 10 studies of reference pricing and one study of index pricing. Most of the reference pricing studies were for senior citizens in British Columbia, Canada. The use (dispensing) of reference drugs increased in five studies, between 60% and 196% immediately after introduction of reference drug pricing, whereas the use of cost sharing drugs decreased by between 19% and 42% in four studies. In three studies the reference drug group expenditures decreased (range 19% - 50%), whereas in the fourth study the expenditures increased by 5% in the short term. The results after six months of reference pricing do not show any clear pattern in relationship to the immediate effects. We found no evidence of adverse effects on health and no clear evidence of increased health care utilisation. For index pricing the evidence was much more limited than for reference drug pricing. A small reduction in drug prices was found. AUTHORS' CONCLUSIONS: We found relatively few studies of pricing policies. The majority of the studies dealt with reference pricing. They had few methodological limitations. Based on the evidence in this review, mostly from senior citizens in British Columbia, Canada, reference drug pricing can reduce third party drug expenditures by inducing a shift in drug use towards less expensive drugs. We found no evidence of adverse effects on health and no clear evidence of increased health care utilisation. The analysis and reporting of the effects on patient drug expenditures were limited in the included studies and administration costs were not reported.

Methods of consumer involvement in developing healthcare policy and research, clinical practice guidelines and patient information material.

BACKGROUND: The importance of consumer involvement in health care is widely recognised. Consumers can be involved in developing healthcare policy and research, clinical practice guidelines and patient information material, through consultations to elicit their views or through collaborative processes. Consultations can be single events, or repeated events, large or small scale. They can involve individuals or groups of consumers to allow debate; the groups may be convened especially for the consultation or be established consumer organisations. They can be organised in different forums and through different media. We anticipated finding few comparative evaluations that reliably evaluated the effects of consumer involvement. OBJECTIVES: To assess the effects of consumer involvement and compare different methods of involvement in developing healthcare policy and research, clinical practice guidelines, and patient information material. SEARCH STRATEGY: We searched: the Cochrane Consumers and Communication Review Group's Specialised Register (4 May 2006); the Cochrane Controlled Trials Register (CENTRAL) (The Cochrane Library, Issue 1 2006), MEDLINE (1966 to January Week 2 2006); EMBASE (1980 to Week 03 2006); CINAHL (1982 to December Week 2 2005), PsycINFO (1806 to January Week 3 2006); Sociological Abstracts (1952 to 24 January 2006); and SIGLE (System for Information on Grey Literature in Europe) (1980 to 2003/1). We scanned reference lists from relevant articles and contacted authors. SELECTION CRITERIA: Randomised and quasi-randomised trials, interrupted time series analyses, and controlled before-after studies assessing methods for involving consumers in developing healthcare policy and research, clinical practice guidelines or patient information material. The outcome measures were: participation or response rates of consumers; consumer views elicited; consumer influence on decisions, healthcare outcomes or resource utilisation; consumers' or professionals' satisfaction with the involvement process or resulting products; impact on the participating consumers; costs. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed their quality and extracted data. We contacted study authors for clarification and to seek missing data. We presented results in a narrative summary and pooled data as appropriate. MAIN RESULTS: Five randomised controlled trials of moderate or low methodological quality involving 1031 participants were included. There is moderate quality evidence that involving consumers in the development of patient information material results in material that is more relevant, readable and understandable to patients, without affecting their anxiety. This 'consumer-informed' material can also improve patients' knowledge. There is low quality evidence that using consumer interviewers instead of staff interviewers in satisfaction surveys can have a small influence on the survey results. There is very low quality evidence of telephone discussions and face-to-face group meetings engaging consumers better than mailed surveys in order to set priorities for community health goals, and resulting in different priorities being set for these goals. AUTHORS' CONCLUSIONS: There is little evidence from comparative studies of the effects of consumer involvement in healthcare decisions at the population level. The studies included in this review demonstrate that randomised controlled trials are feasible for providing evidence about the effects of consulting consumers to inform these decisions.

Chemotherapy for advanced non-small-cell lung cancer: how much benefit is enough?

PURPOSE: To estimate the impact of chemotherapy on survival of patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Randomized controlled trials (RCTs) published in the English-language medical literature between 1970 and 1991 were identified through MEDLINE and the reference lists of relevant articles. Six RCTs that accounted for 635 patients and compared first-line chemotherapy with supportive care in advanced NSCLC and reported survival up to at least 1 year were identified. Cumulative proportions of survival at 3, 6, 9, and 12 months for chemotherapy and control groups were derived from survival curves. RESULTS: Within each study, the effect of chemotherapy was estimated with a pooled relative risk (RR) across the four 3-month periods. An overall estimate of the RR of death at 1 year (RRM-H) was then calculated and a survival curve for chemotherapy-treated patients was constructed applying the pooled estimate of the RR (RRW) for each 3-month period. Overall, chemotherapy was associated with a 24% (95% confidence interval [CI], 13% to 34%) reduction in the probability of death when compared with supportive care. However, the effect of treatment appeared to decrease significantly after the first 6 months from therapy inception and the mean potential gain in survival, as compared with supportive care, was approximately 6 weeks (95% CI, 1 to 10). CONCLUSION: Chemotherapy is effective in the treatment of advanced NSCLC, but its impact on the length of survival is limited. Future RCTs should still include an untreated control group and should measure quality of life in addition to survival.