Identification of topics for comparative effectiveness systematic reviews in the field of cancer imaging.

AIM: With rapid innovations in diagnostic and therapeutic interventions in cancer care, comparative effectiveness reviews (CERs) are essential to inform clinical practice and guide future research. However, the optimal means to identify priority CER topics are uninvestigated. We aimed to devise a transparent and reproducible process to identify ten to 12 CER topics in the area of cancer imaging relevant to a wide range of stakeholders. MATERIALS & METHODS: Environmental scans and explicit prioritization criteria supported interactions (email communications, web-based discussions and live teleconferences) with experts and stakeholders culminating in a three-phase deductive exercise for prioritization of CER topics. RESULTS: We prioritized 12 CER topics in breast, lung and gastrointestinal cancers that addressed screening, diagnosis, staging, monitoring and evaluating response to treatment. CONCLUSION: Our project developed and implemented a transparent and reproducible process for research prioritization and topic nomination that can be further refined to improve the relevance of future CERs.

Empirical evaluation of meta-analytic approaches for nutrient and health outcome dose-response data.

The objective of this study is to empirically compare alternative meta-analytic methods for combining dose-response data from epidemiological studies. We identified meta-analyses of epidemiological studies that analyzed the association between a single nutrient and a dichotomous outcome. For each topic, we performed meta-analyses of odds ratios with five approaches: using extreme exposure categories only, two-step approach (first calculated study-specific effects then combined across studies) using unadjusted data, two-step approach using adjusted data, one-step approach (analyzed all data in one regression model) using unadjusted data, and one-step approach using adjusted data. Meta-analyses including only extreme exposure categories gave consistently bigger effects and wider confidence intervals than meta-analyses using all data. Confidence intervals of effect sizes were generally wider in meta-analyses with the two-step approach, compared with the one-step approach. Meta-analyses using unadjusted data and adjusted data differed, with no consistent pattern of discordance in direction, statistical significance, or magnitude of effect. We discourage using meta-analysis approaches that only use data from extreme exposure categories. The one-step approach generally has higher precision than the two-step approach. Sensitivity analysis comparing results between meta-analyses of adjusted and unadjusted data may be useful in indicating the presence of confounding.

Two methods provide similar signals for the need to update systematic reviews.

OBJECTIVE: Apply and compare two methods that identify signals for the need to update systematic reviews, using three Evidence-based Practice Center reports on omega-3 fatty acids as test cases. STUDY DESIGN AND SETTING: We applied the RAND method, which uses domain (subject matter) expert guidance, and a modified Ottawa method, which uses quantitative and qualitative signals. For both methods, we conducted focused electronic literature searches of recent studies using the key terms from the original reports. We assessed the agreement between the methods and qualitatively assessed the merits of each system. RESULTS: Agreement between the two methods was "substantial" or better (kappa>0.62) in three of the four systematic reviews. Overall agreement between the methods was "substantial" (kappa=0.64, 95% confidence interval [CI] 0.45-0.83). CONCLUSION: The RAND and modified Ottawa methods appear to provide similar signals for the possible need to update systematic reviews in this pilot study. Future evaluation with a broader range of clinical topics and eventual comparisons between signals to update reports and the results of full evidence review updates will be needed. We propose a hybrid approach combining the best features of both methods, which should allow efficient review and assessment of the need to update.

Active surveillance in men with localized prostate cancer: a systematic review.

BACKGROUND: Active surveillance (AS) and watchful waiting (WW) have been proposed as management strategies for low-risk, localized prostate cancer. PURPOSE: To systematically review strategies for observational management of prostate cancer (AS or WW), factors affecting their utilization, and comparative effectiveness of observational management versus immediate treatment with curative intent. DATA SOURCES: MEDLINE and Cochrane databases (from inception to August 2011). STUDY SELECTION: Screened abstracts and reviewed full-text publications to identify eligible studies. DATA EXTRACTION: One reviewer extracted data, and another verified quantitative data. Two independent reviewers rated study quality and strength of evidence for comparative effectiveness. DATA SYNTHESIS: Sixteen independent cohorts defined AS, 42 studies evaluated factors that affect the use of observational strategies, and 2 evidence reports and 22 recent studies reported comparisons of WW versus treatment with curative intent. The most common eligibility criteria for AS were tumor stage (all cohorts), Gleason score (12 cohorts), prostate-specific antigen (PSA) concentration (10 cohorts), and number of biopsy cores positive for cancer (8 cohorts). For monitoring, studies used combinations of periodic PSA testing (all cohorts), digital rectal examination (14 cohorts), and rebiopsy (14 cohorts). Predictors of receiving no active treatment included older age, comorbid conditions, lower Gleason score, tumor stage, PSA concentration, and favorable risk group. No published studies compared AS with immediate treatment with curative intent. Watchful waiting was generally less effective than treatment with curative intent; however, applicability to contemporary patients may be limited. LIMITATIONS: Active surveillance and WW often could not be differentiated in the reviewed studies. Published randomized trials have assessed only WW and did not enroll patients diagnosed by PSA screening. CONCLUSION: Evidence is insufficient to assess whether AS is an appropriate option for men with localized prostate cancer. A standard definition of AS that clearly distinguishes it from WW is needed to clarify scientific discourse. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Concordance of randomized and nonrandomized studies was unrelated to translational patterns of two nutrient-disease associations.

OBJECTIVE: There are several examples in nutrition of discordance between the results of observational studies and randomized controlled trials (RCTs). We hypothesized that this discordance is attributable to differences in the translational paths of nutrient-disease associations. Translational paths can be assessed using citation analysis. STUDY DESIGN AND SETTING: We compared the characteristics of citation networks using examples, where RCTs and observational studies agreed (long-chain n-3 polyunsaturated fatty acids [n-3 PUFA]) or disagreed (vitamin E). We performed systematic reviews in each example, constructed citation networks, and compared them with respect to the number of articles and citation relationships between them, as well as the distribution of articles' hub and authority scores. RESULTS: For n-3 PUFA, meta-analyses of 14 RCTs and 10 observational studies both suggested that higher intake was associated with lower cardiovascular mortality. For vitamin E, the meta-analysis of 14 RCTs excluded a clinically significant effect, whereas 14 observational studies reported a significant inverse association. The respective citation networks consisted of 392 (n-3 PUFA) and 351 (vitamin E) articles. No differences between the characteristics of the two networks were identified. There was no evidence that the observational studies predated RCTs in the translational process in either example. CONCLUSION: In the two examples, citation network characteristics do not predict concordance in the results of observational studies and RCTs.

Comparative evaluation of radiation treatments for clinically localized prostate cancer: an updated systematic review.

BACKGROUND: Radiation therapy is one of many treatment options for patients with prostate cancer. PURPOSE: To update findings on the clinical and biochemical outcomes of radiation therapies for localized prostate cancer. DATA SOURCES: MEDLINE (2007 through March 2011) and the Cochrane Central Register of Controlled Trials (2007 through March 2011). STUDY SELECTION: Published English-language comparative studies involving adults with localized prostate cancer who either had first-line radiation therapy or received no initial treatment. DATA EXTRACTION: 6 researchers extracted information on study design, potential bias, sample characteristics, interventions, and outcomes and rated the strength of overall evidence. Data for each study were extracted by 1 reviewer and confirmed by another. DATA SYNTHESIS: 75 studies (10 randomized, controlled trials [RCTs] and 65 nonrandomized studies) met the inclusion criteria. No RCTs compared radiation therapy with no treatment or no initial treatment. Among the 10 RCTs, 2 compared combinations of radiation therapies, 7 compared doses and fraction sizes of external-beam radiation therapy (EBRT), and 1 compared forms of low-dose rate radiation therapy. Heterogeneous outcomes were analyzed. Overall, moderate-strength evidence consistently showed that a higher EBRT dose was associated with increased rates of long-term biochemical control compared with lower EBRT dose. The body of evidence was rated as insufficient for all other comparisons. LIMITATIONS: Studies inconsistently defined and reported outcomes. Much of the available evidence comes from observational studies with treatment selection biases. CONCLUSION: A lack of high-quality comparative evidence precludes conclusions about the efficacy of radiation treatments compared with no treatments for localized prostate cancer. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

An evidence review of active surveillance in men with localized prostate cancer.

BACKGROUND: Radical prostatectomy and radiation therapy for prostate cancer have side effects and unclear survival benefits for early stage and low-risk disease. Prostate cancer often has an indolent natural history, making observational management strategies potentially appealing. PURPOSE: To systematically review the role of active surveillance for triggers to begin curative treatment in men with low-risk prostate cancer. Key Questions address changes in prostate cancer characteristics over time, definitions of active surveillance and other observational strategies, factors affecting the offer of, acceptance of, and adherence to active surveillance, the comparative effectiveness of active surveillance with curative treatments, and research gaps. DATA SOURCES: MEDLINE(®), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and existing systematic reviews, evidence reports, and economic evaluations. STUDY SELECTION: Randomized controlled trials and nonrandomized comparative studies of treatments, multivariable association studies, and studies of temporal trends in prostate cancer natural history. Only published, peer-reviewed, English-language articles were selected based on predetermined eligibility criteria. DATA EXTRACTION: A standardized protocol was used to extract details on design, diagnoses, interventions, predictive factors, outcomes, and study validity. DATA SYNTHESIS: In total, 80 studies provided information on epidemiologic trends; 56 on definitions of active surveillance; 42 on factors affecting the offer of, acceptance of, or adherence to observational management strategies; and 26 on comparative effectiveness. Increased diagnosis of early-stage prostate cancer due to prostate-specific antigen (PSA) testing, led to an increase in prostate cancer incidence from the mid-1980s to the mid-1990s. The prostate cancer-specific mortality rate decreased for all age groups from the early-1990s to 1999. Currently, patients are diagnosed with earlier stage and lower risk prostate cancers compared to the pre-PSA era. Over time, a lower proportion of men received observational management versus active treatment, even among those with low-risk disease. There was no standardized definition of active surveillance. Sixteen cohorts used different monitoring protocols, all with different combinations of periodic digital rectal examination, PSA testing, rebiopsy, and/or imaging findings. Predictors that a patient received no initial active treatment generally included older age, presence of comorbidities, lower Gleason score, lower tumor stage, lower diagnostic PSA, and lower disease progression risk group. No trial provided results comparing men with localized disease on active surveillance with surgery or radiation therapy. LIMITATIONS: Because of the nonstandardized usages of the terms "active surveillance" and "watchful waiting" and their intended and often mixed (both curative and palliative) treatment objectives, it was difficult to determine which study patients received active monitoring for triggers indicative of curative treatment and which observation for clinical symptoms indicative of palliative treatment. CONCLUSIONS: More men are being diagnosed with early stage prostate cancer. Whether active monitoring with a curative intent is an appropriate option for these men remains unclear. A standard, universally agreed-upon definition of active surveillance that clearly distinguishes it from watchful waiting and other observational management strategies is needed to help clarify scientific discourse on this topic. Ongoing clinical trials may provide information on the comparative effectiveness of active surveillance compared to immediate active treatment, but will require long term followup.

Reporting of systematic reviews of micronutrients and health: a critical appraisal.

BACKGROUND: The quality of nutrition-related systematic reviews (SRs) is an unstudied but important factor affecting their usefulness. OBJECTIVES: The objectives were to evaluate the reporting quality of published SRs and to identify areas of improvement. DESIGN: Descriptive and exploratory analyses of the reporting quality (7 nutrition items and 28 SR reporting items) of all English-language SRs published through July 2007 linking micronutrients and health outcomes in humans were conducted. Factors that may be associated with reporting quality were also evaluated. RESULTS: We identified 141 eligible SRs of 21 micronutrients. Ninety SRs that included only interventional studies met a higher proportion of our reporting criteria (median: 62%; interquartile range: 51%, 72%) than did 31 SRs with only observational studies (median: 53%; interquartile range: 47%, 60%) or 20 SRs with both study designs (median: 47%; interquartile range: 39%, 52%) (P < 0.001). SRs published after consensus reporting standards (since 2003) met a higher proportion of the reporting criteria than did earlier SRs (median: 59% compared with 50%; P = 0.01); however, the reporting of nutrition variables remained unchanged (median: 38% compared with 33%; P = 0.7). The least-reported nutrition criteria were baseline nutrient exposures (28%) and effects of measurement errors from nutrition exposures (24%). Only 58 SRs (41%) used quality scales or checklists to assess the methodologic quality of the primary studies included. CONCLUSIONS: The reporting quality of SRs has improved 3 y after publication of SR reporting standards, but the reporting of nutrition variables has not. Improved adherence to consensus methods and reporting standards should improve the utility of nutrition SRs.

Modified MyPyramid for Older Adults.

In 1999 we proposed a Modified Food Guide Pyramid for adults aged 70+ y. It has been extensively used in a variety of settings and formats to highlight the unique dietary challenges of older adults. We now propose a Modified MyPyramid for Older Adults in a format consistent with the MyPyramid graphic. It is not intended to substitute for MyPyramid, which is a multifunctional Internet-based program allowing for the calculation of individualized food-based dietary guidance and providing supplemental information on food choices and preparation. Pedagogic issues related to computer availability, Web access, and Internet literacy of older adults suggests a graphic version of MyPyramid is needed. Emphasized are whole grains and variety within the grains group; variety and nutrient density, with specific emphasis on different forms particularly suited to older adults' needs (e.g. frozen) in the vegetables and fruits groups; low-fat and non-fat forms of dairy products including reduced lactose alternatives in the milk group; low saturated fat and trans fat choices in the oils group; and low saturated fat and vegetable choices in the meat and beans group. Underlying themes stress nutrient- and fiber-rich foods within each group and food sources of nutrients rather than supplements. Fluid and physical activity icons serve as the foundation of MyPyramid for Older Adults. A flag to maintain an awareness of the potential need to consider supplemental forms of calcium, and vitamins D and B-12 is placed at the top of the pyramid. Discussed are newer concerns about potential overnutrition in the current food landscape available to older adults.