Faculty Bibliography

Background/UNASSIGNED:Active surveillance (AS) is the most rapidly expanding management option for favorable-risk prostate cancer (PCa). Early studies suggested substantial decrements in utility (quality of life weights) from disease-related anxiety. Our objective was to determine utilities for contemporary AS patients using different instruments. Methods/UNASSIGNED:We performed a systematic review of PubMed, PMC and OVID for utility measurements in modern AS patients. We then examined utilities among 37 men on AS participating in focus groups between 2015-2016 using the generic EurQol five dimensions questionnaire (EQ-5D-3L) and Patient Oriented Prostate Utility Scale (PORPUS), a PCa-specific instrument. Results/UNASSIGNED:The systematic review found previous studies with utilities for PCa treatment and historical watchful waiting populations, but none specifically in contemporary AS. In our AS population, the mean EQ-5D-3L score was 0.90±0.16 (median, 1.00; range, 0.21-1.00) and PORPUS was 0.98±0.03 (median, 0.99; range, 0.84-1.00). The Spearman correlation between the EQ-5D-3L and PORPUS was 0.87 (P<0.0001), and 38% of patients had a difference >0.1 between instruments. Conclusions/UNASSIGNED:Most contemporary AS patients had high utility scores suggesting that they perceive themselves in good health without a major decrement in quality of life from the disease. However, some patients had substantial differences in utility measured with generic versus disease-specific instruments. Further study is warranted into the optimal instrument for utility assessment in contemporary AS patients.

OBJECTIVE:Lung cancer is the leading cause of non-AIDS-defining cancer deaths among HIV-infected individuals. Although lung cancer screening with low-dose computed tomography (LDCT) is endorsed by multiple national organizations, whether HIV-infected individuals would have similar benefit as uninfected individuals from lung cancer screening is unknown. Our objective was to determine the benefits and harms of lung cancer screening among HIV-infected individuals. DESIGN/METHODS:We modified an existing simulation model, the Lung Cancer Policy Model, for HIV-infected patients. DATA SOURCES/METHODS:Veterans Aging Cohort Study, Kaiser Permanente Northern California HIV Cohort, and medical literature. TARGET POPULATION/METHODS:HIV-infected current and former smokers. TIME HORIZON/METHODS:Lifetime. PERSPECTIVE/CONCLUSIONS:Population. INTERVENTION/METHODS:Annual LDCT screening from ages 45, 50, or 55 until ages 72 or 77 years. MAIN OUTCOME MEASURES/METHODS:Benefits assessed included lung cancer mortality reduction and life-years gained; harms assessed included numbers of LDCT examinations, false-positive results, and overdiagnosed cases. RESULTS OF BASE-CASE ANALYSIS/RESULTS:For HIV-infected patients with CD4 cell count at least 500 cells/μl and 100% antiretroviral therapy adherence, screening using the Centers for Medicare & Medicaid Services criteria (age 55-77, 30 pack-years of smoking, current smoker or quit within 15 years of screening) would reduce lung cancer mortality by 18.9%, similar to the mortality reduction of uninfected individuals. Alternative screening strategies utilizing lower screening age and/or pack-years criteria increase mortality reduction, but require more LDCT examinations. LIMITATIONS/CONCLUSIONS:Strategies assumed 100% screening adherence. CONCLUSION/CONCLUSIONS:Lung cancer screening reduces mortality in HIV-infected patients with CD4 cell count at least 500 cells/μl, with a number of efficient strategies for eligibility, including the current Centers for Medicare & Medicaid Services criteria.

OBJECTIVE:To understand the informational needs during active surveillance (AS) for prostate cancer from the perspectives of patients and providers. METHODS:We conducted seven focus groups with 37 AS patients in two urban clinical settings, and 24 semi-structured interviews with a national sample of providers. Transcripts were analyzed using applied thematic analysis, and themes were organized using descriptive matrix analyses. RESULTS:We identified six themes related to informational needs during AS: 1) more information on prostate cancer (biopsy features, prognosis), 2) more information on active surveillance (difference from watchful waiting, testing protocol), 3) more information on alternative management options (complementary medicine, lifestyle modification), 4) greater variety of resources (multiple formats, targeting different audiences), 5) more social support and interaction, and 6) verified integrity of information (trusted, multidisciplinary and secure). CONCLUSIONS:Patients and providers described numerous drawbacks to existing prostate cancer resources and a variety of unmet needs including information on prognosis, AS testing protocols, and lifestyle modification. They also expressed a need for different types of resources, including interaction and unbiased information. PRACTICAL IMPLICATIONS/CONCLUSIONS:These results are useful to inform the design of future resources for men undergoing AS.

INTRODUCTION: We used a computer simulation of HIV progression and transmission to evaluate the cost-effectiveness of a scale-up of three strategies to seek out and test individuals with undiagnosed HIV in New York City (NYC). SETTING: Hypothetical NYC population METHODS:: We incorporated the observed effects and costs of the three "seek and test" strategies in a computer simulation of HIV in NYC, comparing a scenario in which the strategies were scaled up with a one-year implementation or a long-term implementation with a counterfactual scenario with no scale-up. The simulation combined a deterministic compartmental model of HIV transmission with a stochastic microsimulation of HIV progression, calibrated to NYC epidemiological data from 2003 to 2015. The three approaches were respondent driven sampling (RDS) with anonymous HIV testing ("RDS-A"), RDS with a two-session confidential HIV testing approach ("RDS-C"), and venue-based sampling ("VBS"). RESULTS: RDS-A was the most cost-effective strategy tested. When implemented for only one year and then stopped thereafter, using a societal perspective, the cost per quality-adjusted life-year (QALY) gained versus no intervention was $812/QALY, $18,110/QALY, and $20,362/QALY for RDS-A, RDS-C, and VBS, respectively. When interventions were implemented long-term, the cost per QALY gained versus no intervention was cost-saving, $31,773/QALY, and $35,148/QALY for RDS-A, RDS-C, and VBS, respectively. When compared to RDS-A the incremental cost effectiveness ratios (ICERs) for both VBS and RDS-C were dominated. CONCLUSION: The expansion of the RDS-A strategy would substantially reduce HIV-related deaths and new HIV infections in NYC, and would be either cost-saving or have favorable cost-effectiveness.

OBJECTIVE: The purpose of this study is to assess differences in patient distress, risk perception, and treatment preferences for incidental renal findings with descriptive versus combined descriptive and numeric graphical risk information. MATERIALS AND METHODS: A randomized survey study was conducted for adult patients about to undergo outpatient imaging studies at a large urban academic institution. Two survey arms contained either descriptive or a combination of descriptive and numeric graphical risk information about three hypothetical incidental renal findings at CT: 2-cm (low risk) and 5-cm (high risk) renal tumors and a 2-cm (low risk) renal artery aneurysm. The main outcomes were patient distress, perceived risk (qualitative and quantitative), treatment preference, and valuation of lesion discovery. RESULTS: Of 374 patients, 299 participated (79.9% response rate). With inclusion of numeric and graphical, rather than only descriptive, risk information about disease progression for a 2-cm renal tumor, patients reported less worry (3.56 vs 4.12 on a 5-point scale; p < 0.001) and favored surgical consultation less often (29.3% vs 46.9%; p = 0.003). The proportion choosing surgical consultation for the 2-cm renal tumor decreased to a similar level as for the renal artery aneurysm with numeric risk information (29.3% [95% CI, 21.7-36.8%] and 27.9% [95% CI, 20.5-35.3%], respectively). Patients overestimated the absolute risk of adverse events regardless of risk information type, but significantly more so when given descriptive information only, and valued the discovery of lesions regardless of risk information type (range, 4.41-4.81 on a 5-point scale). CONCLUSION: Numeric graphical risk communication for patients about incidental renal lesions may facilitate accurate risk comprehension and support patients in informed decision making.

BACKGROUND:An increasing proportion of prostate cancer is being managed conservatively. However, there are no randomized trials or consensus regarding the optimal follow-up strategy. OBJECTIVE:To compare life expectancy and quality of life between watchful waiting (WW) versus different strategies of active surveillance (AS). DESIGN, SETTING, AND PARTICIPANTS/METHODS:A Markov model was created for US men starting at age 50, diagnosed with localized prostate cancer who chose conservative management by WW or AS using different testing protocols (prostate-specific antigen every 3-6 mo, biopsy every 1-5 yr, or magnetic resonance imaging based). Transition probabilities and utilities were obtained from the literature. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/UNASSIGNED:Primary outcomes were life years and quality-adjusted life years (QALYs). Secondary outcomes include radical treatment, metastasis, and prostate cancer death. RESULTS AND LIMITATIONS/CONCLUSIONS:All AS strategies yielded more life years compared with WW. Lifetime risks of prostate cancer death and metastasis were, respectively, 5.42% and 6.40% with AS versus 8.72% and 10.30% with WW. AS yielded more QALYs than WW except in cohorts age >65 yr at diagnosis, or when treatment-related complications were long term. The preferred follow-up strategy was also sensitive to whether people value short-term over long-term benefits (time preference). Depending on the AS protocol, 30-41% underwent radical treatment within 10 yr. Extending the surveillance biopsy interval from 1 to 5 yr reduced life years slightly, with a 0.26 difference in QALYs. CONCLUSIONS:AS extends life more than WW, particularly for men with higher-risk features, but this is partly offset by the decrement in quality of life since many men eventually receive treatment. PATIENT SUMMARY/UNASSIGNED:More intensive active surveillance protocols extend life more than watchful waiting, but this is partly offset by decrements in quality of life from subsequent treatment.

BACKGROUND:In the USA, an epidemic of opioid overdose deaths is occurring, many of which are from heroin. Combining naloxone distribution with linkage to addiction treatment or pre-exposure prophylaxis (PrEP) for HIV prevention through syringe service programmes has the potential to save lives and be cost-effective. We estimated the outcomes and cost-effectiveness of five alternative strategies: no additional intervention, naloxone distribution, naloxone distribution plus linkage to addiction treatment, naloxone distribution plus PrEP, and naloxone distribution plus linkage to addiction treatment and PrEP. METHODS:We developed a decision analytical Markov model to simulate opioid overdose, HIV incidence, overdose-related deaths, and HIV-related deaths in people who inject drugs in Connecticut, USA. Model input parameters were derived from published sources. We compared each strategy with no intervention, as well as simultaneously considering all strategies. Sensitivity analysis was done for all variables. Linkage to addiction treatment was referral to an opioid treatment programme for methadone. Endpoints were survival, life expectancy, quality-adjusted life-years (QALYs), number and percentage of overdose deaths averted, number of HIV-related deaths averted, total costs (in 2015 US$) associated with each strategy, and incremental cost per QALY gained. FINDINGS/RESULTS:In the base-case analysis, compared with no additional intervention, the naloxone distribution strategy yielded an incremental cost-effectiveness ratio (ICER) of $323 per QALY, and naloxone distribution plus linkage to addiction treatment was cost saving compared with no additional intervention (greater effectiveness and less expensive). The most efficient strategies (ie, those conferring the greatest health benefit for a particular budget) were naloxone distribution combined with linkage to addiction treatment (cost saving), and naloxone distribution combined with PrEP and linkage to addiction treatment (ICER $95 337 per QALY) at a willingness-to-pay threshold of $100 000. In probabilistic sensitivity analysis, the combination of naloxone distribution, PrEP, and linkage to addiction treatment was the optimal strategy in 37% of iterations and the combination of naloxone distribution and linkage to addiction treatment was the optimal strategy in 34% of iterations. INTERPRETATION/CONCLUSIONS:Naloxone distribution through syringe service programmes is cost-effective compared with syringe distribution alone, but when combined with linkage to addiction treatment is cost saving compared with no additional services. A strategy that combines naloxone distribution, PrEP, and linkage to addiction treatment results in greater health benefits in people who inject drugs and is also cost-effective. FUNDING/BACKGROUND:State of Connecticut Department of Public Health and the National Institute of Mental Health.

INTRODUCTION: Given the serious health consequences of discontinuing antiretroviral therapy, randomised control trials of interventions to improve retention in care may be warranted. As funding for global HIV research is finite, it may be argued that choices about sample size should be tied to maximising health. METHODS: For an East African setting, we calculated expected value of sample information and expected net benefit of sampling to identify the optimal sample size (greatest return on investment) and to quantify net health gains associated with research. Two hypothetical interventions were analysed: (1) one aimed at reducing disengagement from HIV care and (2) another aimed at finding/relinking disengaged patients. RESULTS: When the willingness to pay (WTP) threshold was within a plausible range (1-3 x GDP; US$1377-4130/QALY), the optimal sample size was zero for both interventions, meaning that no further research was recommended because the pre-research probability of an intervention's effectiveness and value was sufficient to support a decision on whether to adopt the intervention and any new information gained from additional research would likely not change that decision. In threshold analyses, at a higher WTP of $5200 the optimal sample size for testing a risk reduction intervention was 2750 per arm. For the outreach intervention, the optimal sample size remained zero across a wide range of WTP thresholds and was insensitive to variation. Limitations, including not varying all inputs in the model, may have led to an underestimation of the value of investing in new research. CONCLUSION: In summary, more research is not always needed, particularly when there is moderately robust prestudy belief about intervention effectiveness and little uncertainty about the value (cost-effectiveness) of the intervention. Users can test their own assumptions at http://torchresearch.org.