Supplementing Systematic Review Findings with Healthcare System Data: Pilot Projects from the Agency for Healthcare Research and Quality Evidence-based Practice Center Program.

OBJECTIVES: The US Agency for Healthcare Research and Quality (AHRQ), through the Evidence-based Practice Center (EPC) Program, aims to provide health system decision makers with the highest-quality evidence to inform clinical decisions. However, limitations in the literature may lead to inconclusive findings in EPC systematic reviews (SRs). The EPC Program conducted pilot projects to understand the feasibility, benefits, and challenges of utilizing health system data to augment SR findings to support confidence in healthcare decision-making based on real-world experiences. STUDY DESIGN AND SETTING: Three contractors (each an EPC located at a different health system) selected a recently completed systematic review conducted by their center and identified an evidence gap that electronic health record (EHR) data might address. All pilot project topics addressed clinical questions as opposed to care delivery, care organization, or care disparities topics that are common in EPC reports. Topic areas addressed by each EPC included infantile epilepsy, migraine, and hip fracture. EPCs also tracked additional resources needed to conduct supplemental analyses. The workgroup met monthly in 2022-2023 to discuss challenges and lessons learned from the pilot projects. RESULTS: Two supplemental data analyses filled an evidence gap identified in the systematic reviews (raised certainty of evidence, improved applicability) and the third filled a health system knowledge gap. Project challenges fell under three themes: regulatory and logistical issues, data collection and analysis, and interpretation and presentation of findings. Limited ability to capture key clinical variables given inconsistent or missing data within the EHR was a major limitation. The workgroup found that conducting supplemental data analysis alongside an SR was feasible but adds considerable time and resources to the review process (estimated total hours to complete pilot projects ranged from 283-595 across EPCs), and that the increased effort and resources added limited incremental value. CONCLUSION: Supplementing existing systematic reviews with analyses of EHR data is resource intensive and requires specialized skillsets throughout the process. While using EHR data for research has immense potential to generate real-world evidence and fill knowledge gaps, these data may not yet be ready for routine use alongside systematic reviews.

Utility of beta-lactam allergy assessment in patients receiving vancomycin for surgical prophylaxis.

Background: Beta-lactam antibiotics are first-line agents for most patients receiving antimicrobial prophylaxis in surgical procedures. Despite evidence showing low cross-reactivity between penicillins and cephalosporins, patients with beta-lactam allergies commonly receive vancomycin as an alternative to avoid allergic reaction. Methods: Adult patients receiving vancomycin for surgical prophylaxis with a reported beta-lactam allergy at our institution between August 2017 to July 2018 were retrospectively evaluated for potential eligibility for penicillin allergy testing and/or receipt of standard prophylaxis. Results: Among 830 patients who received vancomycin for surgical prophylaxis, 196 reported beta-lactam allergy and were included in the analysis. Approximately 40 % of surgeries were orthopedic. Of patients receiving vancomycin as first-line therapy, 189 (96.4 %) were potentially eligible for beta-lactam prophylaxis. Conclusions: Patients with beta-lactam allergies often qualify for receipt of a first-line antibiotic. An opportunity exists for improved allergy assessment as an antimicrobial stewardship intervention in surgical prophylaxis.

General Perceptions and Knowledge of Antibiotic Resistance and Antibiotic Use Behavior: A Cross-Sectional Survey of US Adults.

This study aimed to assess understanding of antibiotic resistance and evaluate antibiotic use themes among the general public. In March 2018, respondents that were ≥21 years old and residing in the United States were recruited from ResearchMatch.org and surveyed to collect data on respondent expectations, knowledge, and opinions regarding prescribing antibiotics and antibiotic resistance. Content analysis was used to code open-ended definitions of antibiotic resistance into central themes. Chi-square tests were used to assess differences between the definitions of antibiotic resistance and antibiotic use. Among the 657 respondents, nearly all (99%) had taken an antibiotic previously. When asked to define antibiotic resistance, the definitions provided were inductively coded into six central themes: 35% bacteria adaptation, 22% misuse/overuse, 22% resistant bacteria, 10% antibiotic ineffectiveness, 7% body immunity, and 3% provided an incorrect definition with no consistent theme. Themes that were identified in respondent definitions of resistance significantly differed between those who reported having shared an antibiotic versus those who had not (p = 0.03). Public health campaigns remain a central component in the fight to combat antibiotic resistance. Future campaigns should address the public's understanding of antibiotic resistance and modifiable behaviors that may contribute to resistance.

Major Update 2: Antibody Response and Risk for Reinfection After SARS-CoV-2 Infection-Final Update of a Living, Rapid Review.

BACKGROUND: The durability of the antibody response after SARS-CoV-2 infection and the role of antibodies in protection against reinfection are unclear. PURPOSE: To synthesize evidence on the SARS-CoV-2 antibody response and reinfection risk with a focus on gaps identified in our prior reports. DATA SOURCES: MEDLINE (Ovid), EMBASE, CINAHL, World Health Organization Research Database, and reference lists from 16 December 2021 through 8 July 2022, with surveillance through 22 August 2022. STUDY SELECTION: English-language, cohort studies evaluating IgG antibody duration at least 12 months after SARS-CoV-2 infection, the antibody response among immunocompromised adults, predictors of nonseroconversion, and reinfection risk. DATA EXTRACTION: Two investigators sequentially extracted study data and rated quality. DATA SYNTHESIS: Most adults had IgG antibodies after SARS-CoV-2 infection at time points greater than 12 months (low strength of evidence [SoE]). Although most immunocompromised adults develop antibodies, the overall proportion with antibodies is lower compared with immunocompetent adults (moderate SoE for organ transplant patients and low SoE for patients with cancer or HIV). Prior infection provided substantial, sustained protection against symptomatic reinfection with the Delta variant (high SoE) and reduced the risk for severe disease due to Omicron variants (moderate SoE). Prior infection was less protective against reinfection with Omicron overall (moderate SoE), but protection from earlier variants waned rapidly (low SoE). LIMITATION: Single review for abstract screening and sequential review for study selection, data abstraction, and quality assessment. CONCLUSION: Evidence for a sustained antibody response to SARS-CoV-2 infection is considerable for both Delta and Omicron variants. Prior infection protected against reinfection with both variants, but, for Omicron, protection was weaker and waned rapidly. This information may have limited clinical applicability as new variants emerge. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098).

Opioid and Sedative-Hypnotic Prescriptions Among Post-9/11 Veteran VA Users Nationwide With Traumatic Brain Injury, 2012-2020.

OBJECTIVE: Many post-9/11 Veterans have received Department of Veterans Affairs (VA) healthcare for traumatic brain injury (TBI). Pain conditions are prevalent among these patients and are often managed with opioid analgesics. Opioids may impose unique risks to Veterans with a history of TBI, especially when combined with other psychotropic medications. We examined receipt of opioid and sedative-hypnotic prescriptions among post-9/11 Veterans with TBI who received VA care nationally between 2012 and 2020. SETTING: Nationwide VA outpatient care. PARTICIPANTS: Veterans with, versus without, clinician-confirmed TBI based on the VA's Comprehensive TBI Evaluation (CTBIE) were followed up for subsequent years in which they received VA care. DESIGN: A historical cohort study. MAIN MEASURES: Proportions of Veterans who received opioid, benzodiazepine, and nonbenzodiazepine sedative-hypnotic prescriptions were compared by CTBIE outcome (TBI yes/no) and by year; overlaps between medication classes, long-term opioid therapy, and high-dose opioid therapy were also examined. Among those with confirmed TBI, logistic regression was used to examine associations between veteran characteristics and likelihood of these potentially high-risk opioid use outcomes. RESULTS: Among 69 752 Veterans with clinician-confirmed TBI, 26.9% subsequently received opioids. The prevalence receiving opioids each year increased from 2012 (16.7%) to 2014 (17.7%), and then decreased each of the following years through 2020 (5.8%). Among Veterans with TBI who received opioids, large proportions also received benzodiazepine (30.1%) and nonbenzodiazepine (36.0%) sedative-hypnotic prescriptions; these proportions also decreased in recent years. In both bivariable and multivariable regression models, Veterans' demographic, TBI, and clinical characteristics were associated with likelihood of potentially high-risk opioid use. CONCLUSIONS: VA opioid prescribing to Veterans with TBI has decreased in recent years but remains an important source of risk, particularly when considering coprescriptions of sedative-hypnotic medication. Understanding patterns of psychotropic prescription use among Veterans with TBI can highlight important healthcare and rehabilitation needs in this large patient cohort.

Receipt of Concurrent VA and Non-VA Opioid and Sedative-Hypnotic Prescriptions Among Post-9/11 Veterans With Traumatic Brain Injury.

OBJECTIVE: Receipt of concurrent psychotropic prescription medications from both US Department of Veterans Affairs (VA) and non-VA healthcare providers may increase risk of adverse opioid-related outcomes among veterans with traumatic brain injury (TBI). Little is known about patterns of dual-system opioid or sedative-hypnotic prescription receipt in this population. We estimated the prevalence and patterns of, and risk factors for, VA/non-VA prescription overlap among post-9/11 veterans with TBI receiving opioids from VA providers in Oregon. SETTING: Oregon VA and non-VA outpatient care. PARTICIPANTS: Post-9/11 veterans in Oregon with TBI who received an opioid prescription from VA providers between the years of 2014 and 2019. DESIGN: Historical cohort study. MAIN MEASURES: Prescription overlap of VA opioids and non-VA opioids or sedative-hypnotics; proportions of veterans who received VA or non-VA opioid, benzodiazepine, and nonbenzodiazepine sedative-hypnotic prescriptions were also examined by year and by veteran characteristics. RESULTS: Among 1036 veterans with TBI receiving opioids from the VA, 210 (20.3%) received an overlapping opioid prescription from a non-VA provider; 5.3% received overlapping benzodiazepines; and none received overlapping nonbenzodiazepine sedative-hypnotics. Proportions of veterans with prescription overlap tended to decrease over time. Veterans with other than urban versus urban addresses (OR = 1.4; 95% CI, 1.0-1.8), high versus medium average annual VA visits (OR = 1.7; 95% CI, 1.1-2.6), and VA service connection of 50% or more versus none/0% to 40% (OR = 4.3; 95% CI, 1.3-14.0) were more likely to have concurrent VA/non-VA prescriptions in bivariable analyses; other than urban remained associated with overlap in multivariable models. Similarly, veterans with comorbid posttraumatic stress disorder diagnoses were more likely to have concurrent VA/non-VA prescriptions in both bivariable and multivariable (OR = 2.1; 95% CI, 1.0-4.1) models. CONCLUSION: Among post-9/11 veterans with TBI receiving VA opioids, a considerable proportion had overlapping non-VA prescription medications. Providers and healthcare systems should consider all sources of psychotropic prescriptions, and risk factors for overlapping medications, to help mitigate potentially unsafe medication use among veterans with TBI.

Mask use in community settings in the context of COVID-19: A systematic review of ecological data.

BACKGROUND: The wearing of medical and non-medical masks by the general public in community settings is one intervention that is important for the reduction of SARS-CoV-2 transmission, and has been the subject of considerable research, policy, advocacy and debate. Several observational studies have used ecological (population-level) data to assess the effect of masks on transmission, hospitalization, and mortality at the region or community level. METHODS: We undertook this systematic review to summarize the study designs, outcomes, and key quality indicators of using ecological data to evaluate the association between mask wearing and COVID-19 outcomes. We searched the World Health Organization (WHO) COVID-19 global literature database up to 5 March 2021 for studies reporting the impact of mask use in community settings on outcomes related to SARS-CoV-2 transmission using ecological data. FINDINGS: Twenty one articles were identified that analysed ecological data to assess the protective effect of policies mandating community mask wearing. All studies reported SARS-CoV-2 benefits in terms of reductions in either the incidence, hospitalization, or mortality, or a combination of these outcomes. Few studies assessed compliance to mask wearing policies or controlled for the possible influence of other preventive measures such as hand hygiene and physical distancing, and information about compliance to these policies was lacking. INTERPRETATION: Ecological studies have been cited as evidence to advocate for the adoption of universal masking policies. The studies summarized by this review suggest that community mask policies may reduce the population-level burden of SARS-CoV-2. Methodological limitations, in particular controlling for the actual practice of mask wearing and other preventive policies make it difficult to determine causality. There are several important limitations to consider for improving the validity of ecological data.

Efficacy, Safety, and Timing of Anticoagulant Thromboprophylaxis for the Prevention of Venous Thromboembolism in Patients With Acute Spinal Cord Injury: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: The objective of this study was to answer 5 key questions: What is the comparative effectiveness and safety of (1a) anticoagulant thromboprophylaxis compared to no prophylaxis, placebo, or another anticoagulant strategy for preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) after acute spinal cord injury (SCI)? (1b) Mechanical prophylaxis strategies alone or in combination with other strategies for preventing DVT and PE after acute SCI? (1c) Prophylactic inferior vena cava filter insertion alone or in combination with other strategies for preventing DVT and PE after acute SCI? (2) What is the optimal timing to initiate and/or discontinue anticoagulant, mechanical, and/or prophylactic inferior vena cava filter following acute SCI? (3) What is the cost-effectiveness of these treatment options? METHODS: A systematic literature search was conducted to identify studies published through February 28, 2015. We sought randomized controlled trials evaluating efficacy and safety of antithrombotic strategies. Strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Nine studies satisfied inclusion criteria. We found a trend toward lower risk of DVT in patients treated with enoxaparin. There were no significant differences in rates of DVT, PE, bleeding, and mortality between patients treated with different types of low-molecular-weight heparin or between low-molecular-weight heparin and unfractionated heparin. Combined anticoagulant and mechanical prophylaxis initiated within 72 hours of SCI resulted in lower risk of DVT than treatment commenced after 72 hours of injury. CONCLUSION: Prophylactic treatments can be used to lower the risk of venous thromboembolic events in patients with acute SCI, without significant increase in risk of bleeding and mortality and should be initiated within 72 hours.

Timing of Decompression in Patients With Acute Spinal Cord Injury: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVE: To conduct a systematic review and synthesis of the literature to assess the comparative effectiveness, safety, and cost-effectiveness of early (≤24 hours) versus late decompression (>24 hours) in adults with acute spinal cord injury (SCI). METHODS: A systematic search was conducted of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar to identify studies published through November 6, 2014. Studies published in any language, in humans, and with an abstract were considered for inclusion. Included studies were critically appraised and the overall strength of evidence was determined using methods proposed by the Grading of Recommendation Assessment, Development and Evaluation working group. RESULTS: The search yielded 449 potentially relevant citations. Sixteen additional primary studies were identified through other sources. Six studies met inclusion criteria. All but 2 studies were considered to have moderately high risk of bias. Across studies and injury levels, the impact of early surgical decompression (≤24 hours) on clinically important improvement in neurological status was variable. Isolated studies reported statistically significant and clinically important improvements at 6 months (cervical injury, low strength of evidence) and following discharge from inpatient rehabilitation (all levels, very low strength of evidence) but not at other time points; another study observed a statistically significant 6 point improvement in ASIA Impairment Scale (AIS) among patients with AIS B, C, or D, but not for those with AIS A (very low strength of evidence). In one study of acute central cord syndrome without instability, a clinically and statistically meaningful improvement in total motor scores was reported at 6 and 12 months in patients treated early (versus late). There were, however, no significant differences in AIS improvement between early and late surgical groups at 6- or 12-months (very low strength of evidence). One of 3 studies found a shorter length of hospital stay associated with early surgical decompression. Of 3 studies reporting on safety, no significant differences in rates of complications (including mortality, neurologic deterioration, pneumonia or pressure ulcers) were noted between early and late decompression groups. CONCLUSIONS: Results surrounding the efficacy of early versus late decompressive surgery, as well as the quality of evidence available, were variable depending on the level of SCI, timing of follow-up, and specific outcome considered. Existing evidence supports improved neurological recovery among cervical SCI patients undergoing early surgery; however, evidence regarding remaining SCI populations and clinical outcomes was inconsistent.

Limitations of A Measurement Tool to Assess Systematic Reviews (AMSTAR) and suggestions for improvement.

A Measurement Tool to Assess Systematic Reviews (AMSTAR) is a commonly used tool to assess the quality of systematic reviews; however, modifications are needed to improve its usability, reliability, and validity. In this commentary, we summarize our experience and the experiences of others who have used AMSTAR and provide suggestions for its improvement. We propose that AMSTAR should modify a number of individual items and their instructions and responses to make them more congruent with an assessment of the methodologic quality of systematic reviews. We recommend adding new items and modifying existing items to assess the quality of the body of evidence and to address subgroup and sensitivity analyses. More detailed instructions are needed for scoring individual items across multiple reviewers, and we recommend that a total score should not be calculated. These suggestions need to be empirically tested prior to implementation.

Change score or follow-up score? Choice of mean difference estimates could impact meta-analysis conclusions.

OBJECTIVES: In randomized controlled clinical trials, continuous outcomes are typically measured at both baseline and follow-up, and mean difference could be estimated using the change scores from baseline or the follow-up scores. This study assesses the impact of using change score vs. follow-up score on the conclusions of meta-analyses. STUDY DESIGN AND SETTING: A total of 63 meta-analyses from six comparative effectiveness reviews were included. The combined mean difference was estimated using a random-effects model, and we also evaluated whether the impact qualitatively varied by alternative random-effects estimates. RESULTS: Based on the Dersimonian-Laird (DL) method, using the change vs. the follow-up score led to five meta-analyses (7.9%) showing discrepancy in conclusions. Based on the profile likelihood (PL) method, nine (14.3%) showed discrepancy in conclusions. Using change score was more likely to show a significant difference in effects between interventions (DL method: 4 of 5; PL method: 7 of 9). A significant difference in baseline scores did not necessarily lead to discrepancies in conclusions. CONCLUSIONS: Using the change vs. the follow-up score could lead to important discrepancies in conclusions. Sensitivity analyses should be conducted to check the robustness of results to the choice of mean difference estimates.

Clinical trial registries are of minimal use for identifying selective outcome and analysis reporting.

OBJECTIVE: This study aimed to examine selective outcome reporting (SOR) and selective analysis reporting (SAR) in randomized controlled trials (RCTs) and to explore the usefulness of trial registries for identifying SOR and SAR. STUDY DESIGN AND SETTING: We selected one "index outcome" for each of three comparative effectiveness reviews (CERs) of pharmacotherapy and extracted data on this outcome from trial registries and from study publications. RESULTS: Among 50 RCTs published since 2005 and reporting the index outcome, only 50% were listed in registries; 90% of RCTs were assessed as having SOR or SAR. The index outcome in the registry was different from that in the publication in 75% of trials in two CERs, and not specified at all in the third. Reported outcomes and analyses were not consistent between the publication's methods section and the results section in 33% and 46% of the two CERs where the index outcome was a benefit. There were no statistically significant predictors of SOR and SAR in our small sample where some predictors lacked variability. CONCLUSION: The SOR and SAR were frequent in this pilot study, and the most common type of SOR was the publication of outcomes that were not pre-specified. Trial registries were of little use in identifying SOR and of no use in identifying SAR.

Conflicts of interest among authors of clinical practice guidelines for glycemic control in type 2 diabetes mellitus.

BACKGROUND: Conflict of interest (COI) is an important potential source of bias in the development of clinical practice guidelines (CPGs). OBJECTIVES: To examine rates of disclosure of COI, including financial interests in companies that manufacture drugs that are recommended in CPGs on glycemic control in type 2 diabetes mellitus, and to explore the relationship between recommendations for specific drugs in a guideline and author COI. METHODS: We identified a cohort of relevant guidelines from the National Guideline Clearinghouse (NGC) and abstracted COI disclosures from all guideline authors for this observational, cross-sectional study. We determined which hypoglycemic drugs were recommended in each guideline, and explored the relationship between specific disclosures and whether a drug was recommended. RESULTS: Among 13 included guidelines, the percentage of authors with one or more financial disclosures varied from 0 to 94% (mean 44.2%), and was particularly high for two US-based guidelines (91% and 94%). Three guidelines disclosed no author financial COI. The percentage of authors with disclosures of financial interests in manufacturers of recommended drugs was also high (mean 30%). On average, 56% of manufacturers of patented drugs recommended in each guideline had one or more authors with a financial interest in their company. We did not find a significant relationship between financial interests and whether a drug was recommended in our sample; US-based guidelines were more likely to make recommendations for a specific drug compared to non-US based guidelines. DISCUSSION: Authors of this cohort of guidelines have financial interests directly related to the drugs that they are recommending. Although we did not find an association between author COI and drugs recommended in these guidelines and we cannot draw conclusions about the validity of the recommendations, the credibility of many of these guidelines is in doubt.

Quality of clinical practice guidelines for glycemic control in type 2 diabetes mellitus.

BACKGROUND: Several studies have reported that clinical practice guidelines (CPGs) in a variety of clinical areas are of modest or variable quality. The objective of this study was to evaluate the quality of an international cohort of CPGs that provide recommendations on pharmaceutical management of glycemic control in patients with type 2 diabetes mellitus (DM2). METHODS AND FINDINGS: We searched the National Guideline Clearinghouse (NGC) on February 15th and June 4th, 2012 for CPGs meeting inclusion criteria. Two independent assessors rated the quality of each CPG using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. Twenty-four guidelines were evaluated, and most had high scores for clarity and presentation. However, scope and purpose, stakeholder involvement, rigor of development, and applicability domains varied considerably. The majority of guidelines scored low on editorial independence, and only seven CPGs were based on an underlying systematic review of the evidence. CONCLUSIONS: The overall quality of CPGs for glycemic control in DM2 is moderate, but there is substantial variability among quality domains within and across guidelines. Guideline users need to be aware of this variability and carefully appraise and select the guidelines that they apply to patient care.

Conflict of interest disclosures for clinical practice guidelines in the national guideline clearinghouse.

BACKGROUND: Conflict of interest (COI) is an important potential source of bias in the development of clinical practice guidelines (CPGs) and high rates of COI among guideline authors have been reported in the past. Our objective was to report current rates of disclosure and specific author COI across a broad range of CPGs and to examine whether CPG characteristics were associated with the presence of disclosures and of conflicts. METHODS AND FINDINGS: We selected a random sample of 250 CPGs listed in the National Guideline Clearinghouse on November 22, 2010, representing approximately a 10% sample of guidelines listed in the NGC on that date. We abstracted information on author COI from each CPG and examined predictors of the disclosures and COI using a logistic generalized estimating equation regression model. 87% of organizations developing guidelines had a CPG-specific policy, however, 40% of CPGs did not indicate that they had collected disclosures from guideline authors. In addition, 42% of organizations that did collect author disclosures did not have those disclosures available in the public domain. Of CPGs where we had disclosures for all authors, 60% had one or more authors with a conflict. On average, 28% of the authors of CPGs with available disclosures had a COI. Guidelines that were published in journals with an impact factor greater than 5.0 were more likely to have one or more authors with a COI than guidelines not published in journals. CONCLUSIONS: Rates of disclosure of author COI and the public availability of that information are unacceptably low, however rates of COI among guideline authors may have decreased in recent years. Continued efforts are needed to establish and enforce optimal COI policies in clinical practice guideline development in order to minimize the risk of bias associated with those conflicts.

Characteristics of physicians receiving large payments from pharmaceutical companies and the accuracy of their disclosures in publications: an observational study.

BACKGROUND: Financial relationships between physicians and industry are extensive and public reporting of industry payments to physicians is now occurring. Our objectives were to describe physician recipients of large total payments from these seven companies, and to examine discrepancies between these payments and conflict of interest (COI) disclosures in authors' concurrent publications. METHODS: The investigative journalism organization, ProPublica, compiled the Dollars for Docs database of payments to individuals from publically available data from seven US pharmaceutical companies during the period 2009 to 2010. We examined the cohort of 373 physicians in this database who each received USD $100,000 or more in the reporting period 2009 to 2010. RESULTS: These physicians received a total of $52,600,624 during this period (mean payment per physician $141,020). The predominant specialties were internal medicine and psychiatry. 147 of these physicians authored a total of 134 publications in the first quarter of 2011 and 77% (103) of these publications provided a COI disclosure. 69% of the 103 publications did not contain disclosures of the payment listed in the Dollars for Docs database. CONCLUSIONS: With increased public reporting of industry payments to physicians, it is apparent that large sums are being paid for services such as consulting and peer education. In over two-thirds of publications where COI disclosures were provided, the disclosures by physician authors did not include industry payments that were documented in the Dollars for Docs database.

Conflict of interest policies for organizations producing a large number of clinical practice guidelines.

BACKGROUND: Conflict of interest (COI) of clinical practice guideline (CPG) sponsors and authors is an important potential source of bias in CPG development. The objectives of this study were to describe the COI policies for organizations currently producing a significant number of CPGs, and to determine if these policies meet 2011 Institute of Medicine (IOM) standards. METHODOLOGY/PRINCIPAL FINDINGS: We identified organizations with five or more guidelines listed in the National Guideline Clearinghouse between January 1, 2009 and November 5, 2010. We obtained the COI policy for each organization from publicly accessible sources, most often the organization's website, and compared those polices to IOM standards related to COI. 37 organizations fulfilled our inclusion criteria, of which 17 (46%) had a COI policy directly related to CPGs. These COI policies varied widely with respect to types of COI addressed, from whom disclosures were collected, monetary thresholds for disclosure, approaches to management, and updating requirements. Not one organization's policy adhered to all seven of the IOM standards that were examined, and nine organizations did not meet a single one of the standards. CONCLUSIONS/SIGNIFICANCE: COI policies among organizations producing a large number of CPGs currently do not measure up to IOM standards related to COI disclosure and management. CPG developers need to make significant improvements in these policies and their implementation in order to optimize the quality and credibility of their guidelines.

Author's specialty and conflicts of interest contribute to conflicting guidelines for screening mammography.

OBJECTIVE: To examine the relationship between guideline panel members' conflicts of interest and guideline recommendations on screening mammography in asymptomatic, average-risk women aged 40-49 years. STUDY DESIGN AND SETTING: We searched the National Guideline Clearinghouse and MEDLINE for relevant guidelines published between January 2005 and June 2011. We examined the disclosures and specialties of the lead and secondary authors of these guidelines, as well as the publications of the lead authors. RESULTS: Twelve guidelines were identified with a total of 178 physician authors from a broad range of specialties. Of the four guidelines not recommending routine screening, none had a radiologist member, whereas of the eight guidelines recommending routine screening, five had a radiologist member (comparison of the proportions, P=0.05). A guideline with radiologist authors was more likely to recommend routine screening (odds ratio=6.05, 95% confidence interval=0.57-∞, P=0.14). The proportion of primary care physicians on guideline panels recommending routine vs. nonroutine screening was significantly different (38% vs. 90% of authors; P=0.01). The odds of a recommendation in favor of routine screening were related to the number of recent publications on breast disease diagnosis and treatment by the lead guideline author (P=0.02). CONCLUSION: Recommendations regarding mammography screening in this target population may reflect the specialty and intellectual interests of the guideline authors.

Conflict of interest in clinical practice guideline development: a systematic review.

BACKGROUND: There is an emerging literature on the existence and effect of industry relationships on physician and researcher behavior. Much less is known, however, about the effects of these relationships and other conflicts of interest (COI) on clinical practice guideline (CPG) development and recommendations. We performed a systematic review of the prevalence of COI and its effect on CPG recommendations. METHODOLOGY/PRINCIPAL FINDINGS: We searched Medline (1980 to March, 2011) for studies that examined the effect of COI on CPG development and/or recommendations. Data synthesis was qualitative. Twelve studies fulfilled inclusion criteria; 9 were conducted in the US. All studies reported on financial relationships of CPG authors with the pharmaceutical industry; 1 study also examined relationships with diagnostic testing and insurance companies. The majority of guidelines had authors with industry affiliations, including consultancies (authors with relationship, range 6-80%); research support (4-78%); equity/stock ownership (2-17%); or any COI (56-87%). Four studies reported multiple types of financial interactions for individual authors (number of types per author: range 2 to 10 or more). Data on the effect of COI on CPG recommendations were confined to case studies wherein authors with specific financial ties appeared to benefit from the related CPG recommendations. In a single study, few authors believed that their relationships influenced their recommendations. No studies reported on intellectual COI in CPGs. CONCLUSIONS/SIGNIFICANCE: There are limited data describing the high prevalence of COI among CPG authors, and only case studies of the effect of COI on CPG recommendations. Further research is needed to explore this potential source of bias.

Quality varies across clinical practice guidelines for mammography screening in women aged 40-49 years as assessed by AGREE and AMSTAR instruments.

OBJECTIVE: To assess the quality of clinical practice guidelines providing recommendations on the frequency of mammography screening in asymptomatic, average-risk women 40-49 years of age. STUDY DESIGN AND SETTING: We searched the National Guideline Clearinghouse and MEDLINE for guidelines published from 2005 to 2010. Five independent assessors rated the quality of each guideline and its underlying evidence review using the Appraisal of Guidelines for Research and Evaluation (AGREE) and Assessment of Multiple Systematic Reviews (AMSTAR) instruments, respectively. RESULTS: Eleven guidelines were appraised. Ten referenced an underlying evidence review; two referenced the same review. Three reviews were rated good, one was moderate, and five were rated poor quality. On overall assessment of the quality of the guidelines, two were strongly recommended, two were recommended with provisos, and seven were either not recommended or the assessors were unsure whether to recommend it. Most guidelines clearly presented their recommendations, but the rigor of development, applicability, and stakeholder involvement varied. Seven guidelines recommended mammography screening as part of a periodic health examination and four recommended individualized screening in the target population. The latter four guidelines were based on good-quality reviews and three were recommended by the assessors. CONCLUSION: Guideline users need to be aware of the variability in quality and identify the high-quality guidelines that meet their needs.