How Do Family Physicians Document Patients' Social Needs in Electronic Health Records?

Social needs are critical determinants of patient health, but their capture in clinical records began recently. A representative survey of family physicians showed that 61% of respondents document social needs using notes, with fewer using diagnosis codes or electronic forms. This preference for unstructured documentation may make it difficult to connect patients across organizations or for policymakers and planners to identify geographic variation in needs.

Estimated travel time and staffing constraints to accessing the Ethiopian health care system: A two-step floating catchment area analysis.

Background: Despite large investments in the public health care system, disparities in health outcomes persist between lower- and upper-income individuals, as well as rural vs urban dwellers in Ethiopia. Evidence from Ethiopia and other low- and middle-income countries suggests that challenges in health care access may contribute to poverty in these settings. Methods: We employed a two-step floating catchment area to estimate variations in spatial access to health care and in staffing levels at health care facilities. We estimated the average travel time from the population centers of administrative areas and adjusted them with provider-to-population ratios. To test hypotheses about the role of travel time vs staffing, we applied Spearman's rank tests to these two variables against the access score to assess the significance of observed variations. Results: Among Ethiopia's 11 first-level administrative units, Addis Ababa, Dire Dawa, and Harari had the best access scores. Regions with the lowest access scores were generally poorer and more rural/pastoral. Approximately 18% of the country did not have access to a public health care facility within a two-hour walk. Our results suggest that spatial access and staffing issues both contribute to access challenges. Conclusion: Investments both in new health facilities and staffing in existing facilities will be necessary to improve health care access within Ethiopia. Because rural and low-income areas are more likely to have poor access, future strategies for expanding and strengthening the health care system should strongly emphasize equity and the role of improved access in reducing poverty.

Equitable Prioritization of Health Interventions by Incorporating Financial Risk Protection Weights Into Economic Evaluations.

OBJECTIVES: Financial risk protection (FRP), or the prevention of medical impoverishment, is a major objective of health systems, particularly in low- and middle-income countries where the extent of out-of-pocket (OOP) health expenditures can be substantial. We sought to develop a method that allows decision makers to explicitly integrate FRP outcomes into their priority-setting activities. METHODS: We used literature review to identify 31 interventions in low- and middle-income countries, each of which provided measures of health outcomes, costs, OOP health expenditures averted, and FRP (proxied by OOP health expenditures averted as a percentage of income), all disaggregated by income quintile. We developed weights drawn from the Z-score of each quintile-intervention pair based on the distribution of FRP of all quintile-intervention pairs. We next ranked the interventions by unweighted and weighted health outcomes for each income quintile. We also evaluated how pro-poor they were by, first, ordering the interventions by cost-effectiveness for each quintile and, next, calculating the proportion of interventions each income quintile would be targeted for a given random budget. A ranking was said to be pro-poor if each quintile received the same or higher proportion of interventions than richer quintiles. RESULTS: Using FRP weights produced a more pro-poor priority setting than unweighted outcomes. Most of the reordering produced by the inclusion of FRP weights occurred in interventions of moderate cost-effectiveness, suggesting that these weights would be most useful as a way of distinguishing moderately cost-effective interventions with relatively high potential FRP. CONCLUSIONS: This preliminary method of integrating FRP into priority-setting would likely be most suitable to deciding between health interventions with intermediate cost-effectiveness.

Residual Disease Burden After Neoadjuvant Therapy Among US Patients With High-Risk HER2-positive Early-Stage Breast Cancer: A Population Effectiveness Model.

BACKGROUND: Approximately half of patients with high-risk HER2-positive early-stage breast cancer (ESBC) do not have pathologic complete response (pCR) after neoadjuvant therapy. The residual burden of disease among this population has not been previously quantified. MATERIALS AND METHODS: We used decision-modeling techniques to simulate recurrence, progression from locoregional to distant cancer, breast cancer-related mortality, and mortality from other causes over a 10-year period in a hypothetical cohort. We derived progression probabilities primarily from the KATHERINE trial of T-DM1 (ado-trastuzumab emtansine) and mortality outcomes from the published literature. Modeled outcomes included recurrences, breast cancer deaths, deaths from other causes, direct medical costs, and costs due to lost productivity. To estimate the residual disease burden, we compared outcomes from a cohort of patients treated with T-DM1 versus a hypothetical cohort with no disease recurrence. RESULTS: We estimated that 9,300 people would experience incident high-risk HER2-positive ESBC in the United States in 2021 based on cancer surveillance databases, clinical trial data, and expert opinion. We estimated that, in this group, 2,118 would experience disease recurrence, including 1,576 distant recurrences, and 1,358 would experience breast cancer deaths. This residual disease burden resulted in 6,435 life-years lost versus the recurrence-free cohort, and healthcare-related costs totaling $644 million, primarily associated with treating distant cancers. CONCLUSION: Patients with HER2-positive ESBC who do not achieve pCR after neoadjuvant therapy are at ongoing risk of recurrence despite the effectiveness of neoadjuvant treatment. There is substantial clinical and economic value in further reducing the residual disease burden in this population.

Implementation of pharmacogenomic clinical decision support for health systems: a cost-utility analysis.

We constructed a cost-effectiveness model to assess the clinical and economic value of a CDS alert program that provides pharmacogenomic (PGx) testing results, compared to no alert program in acute coronary syndrome (ACS) and atrial fibrillation (AF), from a health system perspective. We defaulted that 20% of 500,000 health-system members between the ages of 55 and 65 received PGx testing for CYP2C19 (ACS-clopidogrel) and CYP2C9, CYP4F2 and VKORC1 (AF-warfarin) annually. Clinical events, costs, and quality-adjusted life years (QALYs) were calculated over 20 years with an annual discount rate of 3%. In total, 3169 alerts would be fired. The CDS alert program would help avoid 16 major clinical events and 6 deaths for ACS; and 2 clinical events and 0.9 deaths for AF. The incremental cost-effectiveness ratio was $39,477/QALY. A PGx-CDS alert program was cost-effective, under a willingness-to-pay threshold of $100,000/QALY gained, compared to no alert program.

Economic evaluations of health system strengthening activities in low-income and middle-income country settings: a methodological systematic review.

OBJECTIVE: Health system strengthening (HSS) activities should accompany disease-targeting interventions in low/middle-income countries (LMICs). Economic evaluations provide information on how these types of investment might best be balanced but can be challenging. We conducted a systematic review to evaluate how researchers address these economic evaluation challenges. METHODS: We identified studies about economic evaluation of HSS activities in LMICs using a two-stage approach. First, we conducted a broad search to identify areas where economic evaluations of HSS activities were being conducted. Next, we selected specific interventions for more targeted literature review. We extracted study characteristics using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Finally, we summarised authors' modelling decisions using a framework that examines how models are developed to emphasise generalisability, precision, or realism. FINDINGS: Our searches produced 1978 studies, out of which we included 36. Most studies used data from prospective trials and calculated cost-effectiveness directly from these trial inputs, rather than using simulation methods. As a group, these studies primarily emphasised precision and realism over generalisability, meaning that their results were best suited to specific settings. CONCLUSIONS: The number of included studies was small. Our findings suggest that most economic evaluations of HSS do not leverage methods like sensitivity analyses or inputs from literature review that would produce more generalisable (but potentially less precise) results. More research into how decision-makers would use economic evaluations to define the expansion path to strengthening health systems would allow for conceptualising impactful work on the economic value of HSS.

Assessing the Economic Value of Clinical Artificial Intelligence: Challenges and Opportunities.

OBJECTIVES: Clinical artificial intelligence (AI) is a novel technology, and few economic evaluations have focused on it to date. Before its wider implementation, it is important to highlight the aspects of AI that challenge traditional health technology assessment methods. METHODS: We used an existing broad value framework to assess potential ways AI can provide good value for money. We also developed a rubric of how economic evaluations of AI should vary depending on the case of its use. RESULTS: We found that the measurement of core elements of value-health outcomes and cost-are complicated by AI because its generalizability across different populations is often unclear and because its use may necessitate reconfigured clinical processes. Clinicians' productivity may improve when AI is used. If poorly implemented though, AI may also cause clinicians' workload to increase. Some AI has been found to exacerbate health disparities. Nevertheless, AI may promote equity by expanding access to medical care and, when properly trained, providing unbiased diagnoses and prognoses. The approach to assessment of AI should vary based on its use case: AI that creates new clinical possibilities can improve outcomes, but regulation and evidence collection may be difficult; AI that extends clinical expertise can reduce disparities and lower costs but may result in overuse; and AI that automates clinicians' work can improve productivity but may reduce skills. CONCLUSIONS: The potential uses of clinical AI create challenges for health technology assessment methods originally developed for pharmaceuticals and medical devices. Health economists should be prepared to examine data collection and methods used to train AI, as these may impact its future value.

Economic Evaluation of Urine-Based or Magnetic Resonance Imaging Reflex Tests in Men With Intermediate Prostate-Specific Antigen Levels in the United States.

OBJECTIVES: For men with intermediate prostate-specific antigen (PSA) levels (4-10 ng/mL), urine-based biomarkers and multiparametric magnetic resonance imaging (MRI) are increasingly used as reflex tests before prostate biopsy. We assessed the cost effectiveness of these reflex tests in the United States. METHODS: We used an existing microsimulation model of prostate cancer (PCa) progression and survival to predict lifetime outcomes for a hypothetical cohort of 55-year-old men with intermediate PSA levels. Urine-based biomarkers-PCa antigen (PCA3), TMPRSS2:ERG gene fusion (T2:ERG), and the MyProstateScore (MPS) for any PCa and for high-grade (Gleason score ≥7) PCa (MPShg)-were generated using biomarker data from 1112 men presenting for biopsy at 10 United States institutions. MRI results were based on published sensitivity and specificity for high-grade PCa. Costs and utilities were sourced from literature and Medicare reimbursement schedules. Outcome measures included life years, quality-adjusted life years (QALYs), and lifetime medical costs per patient. Incremental cost-effectiveness ratios were empirically calculated on the basis of simulated life histories under different reflex testing strategies. RESULTS: Biopsying all men provided the most life years and QALYs, followed by reflex testing using MPShg, MPS, MRI, T2:ERG, PCA3, and biopsying no men (QALY range across strategies 15.98-16.09). Accounting for costs, MRI and MPShg were dominated by other strategies. PCA3, T2:ERG, and MPS were likely to be the most cost-effective strategy at willingness-to-pay thresholds of $100 000/QALY, $125 000/QALY, and $150 000/QALY, respectively. CONCLUSIONS: Using PCA3, T2:ERG, or MPS as reflex tests has greater economic value than MRI, biopsying all men, or biopsying no men with intermediate PSA levels.

Clarifying the Trade-Offs of Risk-Stratified Screening for Prostate Cancer: A Cost-Effectiveness Study.

Cancer risk prediction is necessary for precision early detection, which matches screening intensity to risk. However, practical steps for translating risk predictions to risk-stratified screening policies are not well established. We used a validated population prostate-cancer model to simulate the outcomes of strategies that increase intensity for men at high risk and reduce intensity for men at low risk. We defined risk by the Prompt Prostate Genetic Score (PGS) (Stratify Genomics, San Diego, California), a germline genetic test. We first recalibrated the model to reflect the disease incidence observed within risk strata using data from a large prevention trial where some participants were tested with Prompt PGS. We then simulated risk-stratified strategies in a population with the same risk distribution as the trial and evaluated the cost-effectiveness of risk-stratified screening versus universal (risk-agnostic) screening. Prompt PGS risk-adapted screening was more cost-effective when universal screening was conservative. Risk-stratified strategies improved outcomes at a cost of less than $100,000 per quality-adjusted life year compared with biennial screening starting at age 55 years, but risk stratification was not cost-effective compared with biennial screening starting at age 45. Heterogeneity of risk and fraction of the population within each stratum were also important determinants of cost-effectiveness.

Differences in the Selection of Health State Utility Values by Sponsorship in Published Cost-Effectiveness Analyses.

BACKGROUND: Health state utility values (HSUVs) are among the most influential attributes of cost-effectiveness analyses (CEAs). Our objective was to evaluate whether industry-funded studies select systematically different HSUVs as compared with studies without industry funding. METHODS: Among 10 diseases with high disease burden in the United States, we further identified 31 progressive health states. We then searched the Tufts Medical Center's CEA Registry to identify studies that included HSUVs and were submitted to the registry between 2002 and 2019. Two reviewers mapped the free-text descriptions of health states onto the 31 predefined health states. We analyzed the effect of industry funding on the point estimates of these HSUVs with a beta regression. We also analyzed the difference between related health states within studies by funding source with a linear regression. RESULTS: After identifying 26,222 HSUVs from 4198 CEAs, we matched 2573 HSUVs to the 31 predefined health states. We observed large variations within each health state: 12 of 31 health states included a range of HSUVs greater than 0.5. The point estimate model showed 1 statistically significant difference of 31 comparisons between studies with any industry funding and those without. The utility difference model found 3 significant differences out of 39 comparisons between CEAs with any industry funding and those without. LIMITATIONS: Inclusion of unpublished CEAs may have affected our conclusions about the effect of industry funding on selection of HSUVs. We also relied on free-text descriptions of health states available in the CEA Registry and did not include adjustment for multiple comparisons. CONCLUSION: Limited evidence exists that industry-funded studies select different HSUVs compared to non-industry-funded studies for the health states we considered.

Inferring antenatal care visit timing in low- and middle-income countries: Methods to inform potential maternal vaccine coverage.

BACKGROUND: The timing of antenatal care (ANC) visits directly affect health intervention coverage and impact, especially for those interventions requiring strict gestational age windows for administration, such as maternal respiratory syncytial virus (RSV) vaccine. Existing nationally representative population-based surveys do not record the timing of ANC visits beyond the first, limiting the availability of reliable data around timing of subsequent ANC visits in most low- and middle-income countries (LMICs). Here, we describe a model that estimates the timing of ANC visits by gestational age using publicly available multi-country survey data. METHODS AND FINDINGS: We used the Demographic and Health Surveys (DHS) data from 69 LMICs. We used several factors to estimate the timing of subsequent ANC visits by gestation age: the timing of the first ANC visit (ANC1) in a given pregnancy, derived from the DHS; the country's reported average ANC coverage at each ANC visit (ANC1 through the fourth ANC visit [ANC4]); and the World Health Organization's guidance on recommended ANC visit. We then used the timing of ANC visit by gestation age to predict the coverage of a potential maternal RSV vaccine administered at 24-36 weeks of gestation. We calculated the maternal immunization coverage by summing the number of eligible women vaccinated at any ANC visit divided by the total number of pregnant women. We find, in general, countries with higher ANC1 coverage were predicted to have higher vaccination coverage. In 82% of countries, the modeled vaccine coverage is less than ANC4 coverage. CONCLUSIONS: The methods illustrated in this paper have implications on the precision of estimating impact and programmatic feasibility of time-critical interventions, especially for pregnant women. The methods can be easily adapted to vaccine demand forecasts models, vaccine impact assessments, and cost-effectiveness analyses and can be adapted to other maternal interventions that have administration timing restrictions.

Provider preferences for resolving uncertainty and avoiding harms in precision medicine: a discrete choice experiment.

Background: Substantial uncertainty exists about how providers assess the value of genomic testing. Materials & methods: We developed and administered a discrete choice experiment to a national sample of providers. We analyzed responses using an error components mixed logit model. Results: We received responses from 356 providers. The attributes important to providers were patient health and function, life expectancy, cost, expert agreement, and biomarker prevalence. Providers significantly valued reducing uncertainty only when it eliminated the possibility of decreased life expectancy. Providers valued improving certainty about life expectancy gains from 12 ± 18 to 12 ± 6 months at US$400 (US$200-600) versus US$200 (-US$60-500) for 4 ± 4 to 4 ± 2 years. Conclusion: Providers value resolving uncertainty most when it eliminates the possibility of substantial harm.

Forecasting Demand for the Typhoid Conjugate Vaccine in Low- and Middle-income Countries.

BACKGROUND: The World Health Organization (WHO) released a position paper in March 2018 calling for integration of a novel typhoid conjugate vaccine (TCV) into routine immunization along with catch-up campaigns for children up to age 15. Gavi, the Vaccine Alliance, has committed funding to help resource-constrained countries introduce this vaccine. In this article, the Typhoid Vaccine Acceleration Consortium forecasts demand if WHO recommendations are followed. METHODS: We built a model of global TCV introductions between 2020 and 2040 to estimate the demand of the vaccine for 133 countries. We estimated each country's year of introduction by examining its estimated incidence of typhoid fever, its history of introducing new vaccines, and any knowledge we have of its engagement with typhoid prevention, including intention to apply for Gavi funding. Our model predicted use in routine infant vaccination as well as campaigns targeting varying proportions of the unvaccinated population up to 15 years of age. RESULTS: Between 2020 and 2025, demand will predominantly come from African countries, many receiving Gavi support. After that, Asian countries generate most demand until 2030, when campaigns are estimated to end. Demand will then track the birth cohort of participating countries, suggesting an annual routine demand between 90 and 100 million doses. Peak demand is likely to occur between 2023 and 2026, approaching 300 million annual doses if campaign implementation is high. CONCLUSIONS: In our analysis, target population for catch-up campaigns is the main driver of uncertainty. At peak demand, there is some risk of exceeding presently estimated peak production capacity. Therefore, it will be important to carefully coordinate introductions, especially when accompanied by campaigns targeting large proportions of the eligible population.

Cost-Effectiveness of Targeted Pharmacotherapy for Moderate to Severe Plaque Psoriasis.

BACKGROUND: Newer classes of targeted drugs for moderate to severe plaque psoriasis are more effective and more expensive than older classes, posing a difficult and potentially costly decision about whether to use them as initial targeted treatments. OBJECTIVE: To estimate the clinical and economic outcomes of initial targeted treatment for the following drugs: adalimumab, etanercept, and infliximab (TNFα inhibitors); apremilast (PDE4 inhibitor); ustekinumab (IL-12/23 inhibitor); and ixekizumab, secukinumab, and brodalumab (IL-17 inhibitors). METHODS: We developed a Markov model to simulate patient outcomes as measured by quality-adjusted life-years (QALYs) and health care costs over a 10-year period. We assumed that patients who fail initial targeted treatment either proceed to subsequent therapy or discontinue targeted treatment. Effectiveness estimates for initial treatment were defined as improvement in Psoriasis Area and Severity Index (PASI) from baseline and derived from a 2018 network meta-analysis. Wholesale acquisition drug costs were discounted by a class-specific, empirically derived rebate percentage off of 2016 costs. We conducted one-way and probabilistic sensitivity analyses to assess uncertainty in results. RESULTS: The incremental benefits compared with no targeted treatment were, in descending order: ixekizumab 1.68 QALYs (95% credible range [CR] = 1.11-2.02), brodalumab 1.64 QALYs (95% CR = 1.08-1.98), secukinumab 1.51 QALYs (95% CR = 1.00-1.83), ustekinumab 1.43 QALYs (95% CR=0.94-1.74), infliximab 1.27 QALYs (95% CR = 0.89-1.55), adalimumab 1.15 QALYs (95% CR = 0.76-1.44), etanercept 0.97 QALYs (95% CR = 0.61-1.25), and apremilast 0.87 QALYs (95% CR = 0.52-1.17). Costs of care without targeted treatment totaled $66,451, and costs of targeted treatment ranged from $137,080 (apremilast) to $255,422 (ustekinumab). Probabilistic sensitivity analysis results indicated that infliximab and apremilast are likely to be the most cost-effective initial treatments at willingness-to-pay thresholds around $100,000 per QALY, while IL-17 drugs are more likely to be cost-effective at thresholds approaching $150,000 per QALY. Acquisition cost of the initial targeted drug and utility of clinical response were the most influential parameters. CONCLUSIONS: Our findings suggest that initial targeted treatment with IL-17 inhibitors is the most effective treatment strategy for plaque psoriasis patients who have failed methotrexate and phototherapy. Apremilast, brodalumab, infliximab, ixekizumab, and secukinumab are cost-effective at different willingness-to-pay thresholds. Additional research is needed on whether the effectiveness of targeted agents changes when used after previously targeted agents. DISCLOSURES: Funding for this study was contributed by the Institute for Clinical and Economic Review (ICER). Ollendorf, Chapman, Pearson, and Kumar are current employees, and Loos and Liu are former employees, of ICER, an independent organization that evaluates the evidence on the value of health care interventions, which is funded by grants from the Laura and John Arnold Foundation, Blue Shield of California Foundation, and the California HealthCare Foundation. ICER's annual policy summit is supported by dues from Aetna, AHIP, Anthem, Alnylam, AstraZeneca, Blue Shield of California, Cambia Health Solutions and MedSavvy, CVS Caremark, Editas, Express Scripts, Genentech, GlaxoSmithKline, Harvard Pilgrim Health Care, Health Care Service Corporation, OmedaRx, United Healthcare, Johnson & Johnson, Kaiser Permanente, Premera Blue Cross, Merck, National Pharmaceutical Council, Takeda, Pfizer, Novartis, Lilly, Humana, Prime Therapeutics, Sanofi, and Spark Therapeutics. Linder owns stock in Amgen, Biogen, and Eli Lilly; has contingent value rights in Sanofi Genzyme (related to alemtuzumab for multiple sclerosis); has received grant support from Astellas Pharma not related to this study and Clintrex, which was supported by AstraZeneca on an unrelated topic; and has received an honorarium from the Society of Healthcare Epidemiology of America (SHEA) as part of the SHEA Antimicrobial Stewardship Research Workshop Planning Committee, an educational activity supported by Merck. No other authors have potential conflicts of interest.

Integrating value of research into NCI Clinical Trials Cooperative Group research review and prioritization: A pilot study.

BACKGROUND: The Institute of Medicine has called for approaches to help maximize the return on investments (ROI) in cancer clinical trials. Value of Research (VOR) is a health economics technique that estimates ROI and can inform research prioritization. Our objective was to evaluate the impact of using VOR analyses on the clinical trial proposal review process within the SWOG cancer clinical trials consortium. METHODS: We used a previously developed minimal modeling approach to calculate VOR estimates for 9 phase II/III SWOG proposals between February 2015 and December 2016. Estimates were presented to executive committee (EC) members (N = 12) who determine which studies are sent to the National Cancer Institute for funding consideration. EC members scored proposals from 1 (best) to 5 based on scientific merit and potential impact before and after receiving VOR estimates. EC members were surveyed to assess research priorities, proposal evaluation process satisfaction, and the VOR process. RESULTS: Value of Research estimates ranged from -$2.1B to $16.46B per proposal. Following review of VOR results, the EC changed their score for eight of nine proposals. Proposal rankings were different in pre- vs postscores (P value: 0.03). Respondents had mixed views of the ultimate utility of VOR for their decisions with most supporting (42%) or neutral (41%) to the idea of adding VOR to the evaluation process. CONCLUSIONS: The findings from this pilot study indicate use of VOR analyses may be a useful adjunct to inform proposal reviews within NCI Cooperative Clinical Trials groups.

The economic impact of childhood acute gastroenteritis on Malawian families and the healthcare system.

OBJECTIVES: This prospective cohort study sought to estimate health system and household costs for episodes of diarrhoeal illness in Malawi. SETTING: Data were collected in two Malawian settings: a rural health centre in Chilumba and an urban tertiary care hospital in Blantyre. PARTICIPANTS: Children under 5 years of age presenting with diarrhoeal disease between 1 January 2013 and 21 November 2014 were eligible for inclusion. Illnesses attributed to other underlying causes were excluded, as were illnesses commencing more than 2 weeks prior to presentation. Complete data were collected on 514 cases at both the time of the initial visit to the participating healthcare facility and 6 weeks after discharge. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the total cost of an episode of illness. Costs to the health system were gathered from chart review (drugs and diagnostics) and actual hospital expenditure (staff and facility costs). Household costs, including lost income, were obtained by interview with the parents/guardians of patients. RESULTS: Total costs in 2014 US$ for rural inpatient, rural outpatient, urban inpatient and urban outpatient were $65.33, $8.89, $60.23 and $14.51, respectively (excluding lost income). Mean household contributions to these costs were 15.8%, 9.8%, 21.3% and 50.6%. CONCLUSION: This study found significant financial burden from childhood diarrhoeal disease to the healthcare system and to households. The latter face the risk of consequent impoverishment, as the study demonstrates how the costs of seeking treatment bring the income of the majority of families in all income strata below the national poverty line in the month of illness.

Favorable and publicly funded studies are more likely to be published: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to identify and quantify the characteristics of studies associated with the likelihood of publication. STUDY DESIGN AND SETTING: We searched for manuscripts that tracked cohorts of clinical studies ("cohorts") that from launch to publication. We explored the association of study characteristics with the probability of publication via traditional meta-analyses and meta-regression using random effects models. RESULTS: The literature review identified 85 cohorts of studies that met our inclusion criteria. The probability of publication was significantly higher for studies whose characteristics were favorable (odds ratio [OR] = 2.04; 95% confidence interval [CI]: 1.62, 2.57) or statistically significant (OR = 2.07; 95% CI: 1.52, 2.81), had a multicenter design (OR = 1.32; 95% CI: 1.16, 1.45), and were of later regulatory phase (3/4 vs. 1/2, OR = 1.34; 95% CI: 1.14, 1.49). Industry funding was modestly associated with lower (OR = 0.81; 95% CI: 0.67, 0.99) probability of publication. An exploratory analysis of effect modification revealed that the effect of the study characteristic "favorable results" on likelihood for publication was stronger for industry-funded studies. CONCLUSION: The study characteristics of favorable and significant results were associated with greater probability of publication.