Cost Implications for Automaker Compliance of Zero Emissions Vehicle Requirements.

While there are many automotive regulations in the United States, few studies in the literature examine the interaction between different rules. We investigate the cost implications of enforcing the national Corporate Average Fuel Economy (CAFE) and greenhouse gas (GHG) emissions standards and the Zero Emissions Vehicle (ZEV) requirements simultaneously. We construct a new "Cost Optimization Modeling for Efficiency Technologies" (COMET) to understand how vehicle manufacturers implement fuel economy technologies to comply with multiple regulations. We consider a variety of scenarios to measure the interaction between regulations and how they may lead to changes in technology costs. In 2025, unit costs reach $1,600 per vehicle on average to comply with CAFE/GHG and increase to $2,000 per vehicle on average to comply with both CAFE/GHG and ZEV. Unit costs for both regulations are less than the sum of the two because vehicles produced to comply with the ZEV program count toward compliance with the CAFE.

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial.

BACKGROUND: Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS: Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS: 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION: Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING: Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Exploring the Predictors of Organizational Preparedness for Natural Disasters.

There is an extensive body of research on the determinants of disaster preparedness at the individual and household levels. The same cannot be said for the organizational level. Hence, the purpose of this study is to shed light on the predictors of organizational preparedness for natural disasters. Since leaders of organizations have an incentive to overstate their level of preparedness and because surveys of organizational leaders suffer from selection bias and low response rates, we take the novel approach of interviewing employees about the organizations that employ them. Using an online survey, we collected information from a national sample of 2,008 U.S. employees and estimated the predictors of preparedness at the organizational level. We find, among other results, that organization size (facility level) is a consistent predictor of preparedness at the organizational level. We conclude with policy recommendations and outline an agenda for future research on organizational preparedness for natural disasters.

Reducing the risk of injury from table saw use: the potential benefits and costs of automatic protection.

The use of table saws in the United States is associated with approximately 28,000 emergency department (ED) visits and 2,000 cases of finger amputation per year. This article provides a quantitative estimate of the economic benefits of automatic protection systems that could be designed into new table saw products. Benefits are defined as reduced health-care costs, enhanced production at work, and diminished pain and suffering. The present value of the benefits of automatic protection over the life of the table saw are interpreted as the switch-point cost value, the maximum investment in automatic protection that can be justified by benefit-cost comparison. Using two alternative methods for monetizing pain and suffering, the study finds switch-point cost values of $753 and $561 per saw. These point estimates are sensitive to the values of inputs, especially the average cost of injury. The various switch-point cost values are substantially higher than rough estimates of the incremental cost of automatic protection systems. Uncertainties and future research needs are discussed.

Unconventional Gas Development in the USA: Exploring the Risk Perception Issues.

Unconventional gas development (UGD) is growing rapidly in the United States. Drawing on insights from risk perception and risk governance theories and recent public opinion surveys, we find that UGD is an emerging technology that is likely to be perceived as risky, even though objective risk assessments suggest that risks are low and controllable through best risk management practices. Perceived risk varies significantly depending on the state and locality but perceptions of risk appear to be increasing as the technology is used more widely in the United States and as organized opponents of the technology intensify their efforts. Risk perceptions are attenuated somewhat because of the perceived benefits of UGD and compensation schemes for individuals and communities. The types of triggering events necessary for large-scale social amplification and stigmatization have not yet occurred but awareness of UGD is growing and organized opposition has been sufficient to cause prohibitions of UGD in some U.S. states and localities. Additional directions for social science research on public reactions to UGD are recommended.

Escalated-dose versus control-dose conformal radiotherapy for prostate cancer: long-term results from the MRC RT01 randomised controlled trial.

BACKGROUND: The aim of this trial was to compare dose-escalated conformal radiotherapy with control-dose conformal radiotherapy in patients with localised prostate cancer. Preliminary findings reported after 5 years of follow-up showed that escalated-dose conformal radiotherapy improved biochemical progression-free survival. Based on the sample size calculation, we planned to analyse overall survival when 190 deaths occurred; this target has now been reached, after a median 10 years of follow-up. METHODS: RT01 was a phase 3, open-label, international, randomised controlled trial enrolling men with histologically confirmed T1b-T3a, N0, M0 prostate cancer with prostate specific antigen of less than 50 ng/mL. Patients were randomly assigned centrally in a 1:1 ratio, using a computer-based minimisation algorithm stratifying by risk of seminal vesicle invasion and centre to either the control group (64 Gy in 32 fractions, the standard dose at the time the trial was designed) or the escalated-dose group (74 Gy in 37 fractions). Neither patients nor investigators were masked to assignment. All patients received neoadjuvant androgen deprivation therapy for 3-6 months before the start of conformal radiotherapy, which continued until the end of conformal radiotherapy. The coprimary outcome measures were biochemical progression-free survival and overall survival. All analyses were done on an intention-to-treat basis. Treatment-related side-effects have been reported previously. This trial is registered, number ISRCTN47772397. FINDINGS: Between Jan 7, 1998, and Dec 20, 2001, 862 men were registered and 843 subsequently randomly assigned: 422 to the escalated-dose group and 421 to the control group. As of Aug 2, 2011, 236 deaths had occurred: 118 in each group. Median follow-up was 10·0 years (IQR 9·1-10·8). Overall survival at 10 years was 71% (95% CI 66-75) in each group (hazard ratio [HR] 0·99, 95% CI 0·77-1·28; p=0·96). Biochemical progression or progressive disease occurred in 391 patients (221 [57%] in the control group and 170 [43%] in the escalated-dose group). At 10 years, biochemical progression-free survival was 43% (95% CI 38-48) in the control group and 55% (50-61) in the escalated-dose group (HR 0·69, 95% CI 0·56-0·84; p=0·0003). INTERPRETATION: At a median follow-up of 10 years, escalated-dose conformal radiotherapy with neoadjuvant androgen deprivation therapy showed an advantage in biochemical progression-free survival, but this advantage did not translate into an improvement in overall survival. These efficacy data for escalated-dose treatment must be weighed against the increase in acute and late toxicities associated with the escalated dose and emphasise the importance of use of appropriate modern radiotherapy methods to reduce side-effects. FUNDING: UK Medical Research Council.

"Not in (or under) my backyard": Geographic proximity and public acceptance of carbon capture and storage facilities.

Carbon capture and storage (CCS) is an innovative technical approach to mitigate the problem of climate change by capturing carbon dioxide emissions and injecting them underground for permanent geological storage. CCS has been perceived both positively, as an innovative approach to facilitate a more environmentally benign use of fossil fuels while also generating local economic benefits, and negatively, as a technology that prolongs the use of carbon-intensive energy sources and burdens local communities with prohibitive costs and ecological and human health risks. This article extends existing research on the "not in my backyard" (NIMBY) phenomenon in a direction that explores the public acceptance of CCS. We utilize survey data collected from 1,001 residents of the coal-intensive U.S. state of Indiana. Over 80% of respondents express support for the general use of CCS technology. However, 20% of these initial supporters exhibit a NIMBY-like reaction and switch to opposition as a CCS facility is proposed close to their communities. Respondents' worldviews, their beliefs about the local economic benefits that CCS will generate, and their concerns about its safety have the greatest impact on increasing or decreasing the acceptance of nearby facilities. These results lend valuable insights into the perceived risks associated with CCS technology and the possibilities for its public acceptance at both a national and local scale. They may be extended further to provide initial insights into likely public reactions to other technologies that share a similar underground dimension, such as hydraulic fracturing.

Early public impressions of terrestrial carbon capture and storage in a coal-intensive state.

While carbon capture and storage (CCS) is considered to be critical to achieving long-term climate-protection goals, public concerns about the CCS practice could pose significant obstacles to its deployment. This study reports findings from the first state-wide survey of public perceptions of CCS in a coal-intensive state, with an analysis of which factors predict early attitudes toward CCS. Nearly three-quarters of an Indiana sample (N = 1001) agree that storing carbon underground is a good approach to protecting the environment, despite 80% of the sample being unaware of CCS prior to participation in the two-wave survey. The majority of respondents do not hold strong opinions about CCS technology. Multivariate analyses indicate that support for CCS is predicted by a belief that humankind contributes to climate change, a preference for increased use of renewable energy, and egalitarian and individualistic worldviews, while opposition to CCS is predicted by self-identified political conservatism and by selective attitudes regarding energy and climate change. Knowledge about early impressions of CCS can help inform near-term technology decisions at state regulatory agencies, utilities, and pipeline companies, but follow-up surveys are necessary to assess how public sentiments evolve in response to image-building efforts with different positions on coal and CCS.

Internal field distribution measurement in 1-D strongly anisotropic sub-wavelength periodic structures of finite length.

We report measurements of the internal field intensity distribution in finite length one dimensional strongly anisotropic sub-wavelength periodic structures in the vicinity of the photonic band gap (PBG) edge. The strong in-plane anisotropy of more than 10% index contrast is obtained via form birefringent sub-wavelength gratings. The structures have a period of less than half the wavelength. Depending on the excitation frequency, both standing wave and evanescent Bloch modes can be identified and observed experimentally. The field enhancement near the PBG edge is confirmed also but at a significantly reduced strength attributed to the small but finite material loss.

Tunable negative group index in metamaterial structures with large form birefringence.

We experimentally verify the anomalous phase behavior in metamaterial structures with birefringent materials predicted by Mandatori, et. al. using form birefringent structures. Large birefringence as much as Deltan/n = 0.7 has been achieved by surface-treated form birefringent discs, making compact single layer Mandatori structures viable. With a reduced model of a single layer birefringent structure, the relationship between design parameters (thickness and orientation angle) and device operation and performance parameters (such as the center operation frequency, bandwidth, effective negative index, negative group index of refraction, and the transmission throughput) are derived and verified experimentally. Tunable group index of refraction from strong slow light of ng = 29.6 to fast light of ng = -1.1 are measured experimentally.

The benefits and costs of new fuels and engines for light-duty vehicles in the United States.

Rising oil prices and concerns about energy security and climate change are spurring reconsideration of both automobile propulsion systems and the fuels that supply energy to them. In addition to the gasoline internal combustion engine, recent years have seen alternatives develop in the automotive marketplace. Currently, hybrid-electric vehicles, advanced diesels, and flex-fuel vehicles running on a high percentage mixture of ethanol and gasoline (E85) are appearing at auto shows and in driveways. We conduct a rigorous benefit-cost analysis from both the private and societal perspective of the marginal benefits and costs of each technology--using the conventional gasoline engine as a baseline. The private perspective considers only those factors that influence the decisions of individual consumers, while the societal perspective accounts for environmental, energy, and congestion externalities as well. Our analysis illustrates that both hybrids and diesels show promise for particular light-duty applications (sport utility vehicles and pickup trucks), but that vehicles running continuously on E85 consistently have greater costs than benefits. The results for diesels were particularly robust over a wide range of sensitivity analyses. The results from the societal analysis are qualitatively similar to the private analysis, demonstrating that the most relevant factors to the benefit-cost calculations are the factors that drive the individual consumer's decision. We conclude with a brief discussion of marketplace and public policy trends that will both illustrate and influence the relative adoption of these alternative technologies in the United States in the coming decade.

Two-years Postradiotherapy Biopsies: Lessons from MRC RT01 Trial.

BACKGROUND: The importance of 2-yr postradiotherapy prostate biopsy status remains uncertain. OBJECTIVE: To assess the value of 2 year post treatment biopsies in a randomised trial of radiotherapy dose escalation. DESIGN, SETTING, AND PARTICIPANTS: Between 1998 and 2001, 843 men with localised prostate cancer were randomised to receive either control-64Gy or escalated-74Gy conformal radiotherapy (CFRT) in the MRC RT01 trial in combination with 3-6-mo neoadjuvant androgen deprivation therapy. Prostate biopsies were planned at 2 yr from start of CFRT in suitable men. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prostate biopsy results and prostate-specific antigen (PSA) levels performed at 2 yr post-CFRT were evaluated with long-term biochemical progression free survival (bPFS) and overall survival. Outcome measures were timed from the 2-yr biopsy using a landmark approach. RESULTS AND LIMITATIONS: A 2-yr biopsy was performed in 312/843 patients. One hundred and seventy-seven patients were included in the per-protocol group with median follow-up of 7.8 yr from biopsy. Median PSA at biopsy was 0.5ng/ml. Sixty-four bPFS events were reported: 46/145 (32%) in patients with negative, 6/18 (33%) suspicious, and 12/14 (86%) positive biopsies. A positive biopsy was prognostic of worse bPFS, going forward, compared with negative and suspicious biopsies, hazard ratio (HR)=4.81 (95% confidence interval [CI]: 2.50-9.26, p<0.001). The estimate for survival was HR=1.58 (95% CI: 0.52-4.78, p=0.42). PSA values at 2 yr between 1.01ng/ml and 2.09ng/ml were also associated with subsequent PSA failures (HR=2.71, 95% CI: 1.98-3.71), bPFS events (HR=2.45, 95% CI: 1.81-3.32), and prostate cancer-specific survival (HR=2.87, 95% CI: 1.08-7.64) compared with PSA ≤1.0ng/ml. CONCLUSIONS: Two-year postradiotherapy prostate biopsies have limited value in patients with PSA control but both positive biopsy and higher PSA status are strongly associated with future bPFS events. A policy of selected biopsy may provide an opportunity for early salvage interventions. PATIENT SUMMARY: Routine 2-yr postradiotherapy biopsy is not recommended but can be considered in selected patients with unfavourable post-treatment prostate-specific antigen levels who are suitable for early salvage treatments.

Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness.

BACKGROUND: Results from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources. OBJECTIVE: To assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting. DESIGN, SETTING, AND PARTICIPANTS: We modelled health outcomes and costs in the UK NHS using data collected within the STAMPEDE trial, which enrolled men with high-risk, locally advanced metastatic or recurrent PC starting first-line hormone therapy. INTERVENTION: SOC was hormone therapy for ≥2 yr and radiotherapy in some patients. Docetaxel (75mg/m2) was administered alongside SOC for six three-weekly cycles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The model generated lifetime predictions of costs, changes in survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS AND LIMITATIONS: The model predicted that docetaxel would extend survival (discounted quality-adjusted survival) by 0.89 yr (0.51) for metastatic PC and 0.78 yr (0.39) for nonmetastatic PC, and would be cost-effective in metastatic PC (ICER £5514/QALY vs SOC) and nonmetastatic PC (higher QALYs, lower costs vs SOC). Docetaxel remained cost-effective in nonmetastatic PC when the assumption of no survival advantage was modelled. CONCLUSIONS: Docetaxel is cost-effective among patients with nonmetastatic and metastatic PC in a UK setting. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in patients with nonmetastatic PC, as the opportunity to offer docetaxel at hormone therapy initiation will be missed for some patients by the time more mature survival data are available. PATIENT SUMMARY: Starting docetaxel chemotherapy alongside hormone therapy represents a good use of UK National Health Service resources for patients with prostate cancer that is high risk or has spread to other parts of the body.

The early toxicity of escalated versus standard dose conformal radiotherapy with neo-adjuvant androgen suppression for patients with localised prostate cancer: results from the MRC RT01 trial (ISRCTN47772397).

BACKGROUND: Five-year disease-free survival rates for localised prostate cancer following standard doses of conventional radical external beam radiotherapy are around 80%. Conformal radiotherapy (CFRT) raises the possibility that radiotherapy doses can be increased and long-term efficacy outcomes improved, with safety an important consideration. METHODS: MRC RT01 is a randomised controlled trial of 862 men with localised prostate cancer comparing Standard CFRT (64Gy/32f) versus Escalated CFRT (74Gy/37f), both administered with neo-adjuvant androgen suppression. Early toxicity was measured using physician-reported instruments (RTOG, LENT/SOM, Royal Marsden Scales) and patient-reported questionnaires (MOS SF-36, UCLA Prostate Cancer Index, FACT-P). RESULTS: Overall early radiotherapy toxicity was similar, apart from increased bladder, bowel and sexual toxicity, in the Escalated Group during a short immediate post-radiotherapy period. Toxicity in both groups had abated by week 12. Using RTOG Acute Toxicity scores, cumulative Grade 2 bladder and bowel toxicity was 38% and 30% for Standard Group and 39% and 33% in Escalated Group, respectively. Urinary frequency (Royal Marsden Scale) improved in both groups from pre-androgen suppression to 6 months post-radiotherapy (p<0.001), but bowel and sexual functioning deteriorated. This pattern was supported by patient-completed assessments. Six months after starting radiotherapy the incidence of RTOG Grade > or = 2 side-effects was low (<1%); but there were six reports of rectal ulceration (6 Escalated Group), six haematuria (5 Escalated Group) and eight urethral stricture (6 Escalated Group). CONCLUSIONS: The two CFRT schedules with neo-adjuvant androgen suppression have broadly similar early toxicity profiles except for the immediate post-RT period. At 6 months and compared to before hormone therapy, bladder symptoms improved, whereas bowel and sexual symptoms worsened. These assessments of early treatment safety will be complemented by further follow-up to document late side-effects and efficacy.

Rationing decisions and individual responsibility for illness: are all lives equal?

OBJECTIVES: This survey measured individuals' rationing allocation choices for situations in which patients are deemed to hold personal responsibility for their diseases and the influence of different arguments on such choices. METHODS: The association between allocation decisions for liver disease and asthma and the belief that a patient was responsible for his or her illness was modeled using multivariable regression analysis, controlling for the effect of arguments on choices. RESULTS: In data from 310 returned surveys (43% response rate), respondents were 10 to 17 times more likely to allocate liver transplants or asthma treatment to patients they deemed not responsible for their illnesses than to patients they deemed responsible for their conditions (liver transplants: odds ratio [OR] = 10.3, 95% confidence interval ([CI] = 2.5-42.1; asthma: OR = 16.8, 95% CI = 2.1-136.6). CONCLUSIONS: Personal responsibility for illness was an important consideration in respondents' rationing allocation decisions. These choices appeared to be stable although possibly influenced by respondents' interpretations of the survey scenarios and decision tasks.

Assessing preferences for prevention versus treatment using willingness to pay.

BACKGROUND: Rising health care costs and limited resources necessitate trade-offs between resources allocated toward prevention and those toward treatment. Information from opinion polls suggests citizens favor spending a higher proportion of all health care dollars on prevention rather than treatment. OBJECTIVES: To assess the policy implications of willingness to pay (WTP) for use in cost-benefit analysis (CBA) as a method for capturing individual preferences for prevention and treatment in the context of resource allocation decisions. METHODS: The authors recruited a random sample of 1456 US residents age 18 years and greater by telephone using random-digit dialing. The survey was designed as a 3-stage (phone-mail-phone) process and was conducted between December 1998 and March 1999. For all persons completing the survey (N = 1104), the authors 1st collected respondents' opinions about the costs and effectiveness of prevention versus treatment programs in general. Half of respondents were then asked to state their WTP for a hypothetical prevention scenario and half were asked to state their WTP for a hypothetical treatment scenario. Both scenarios were specific to the same health context and included an identical reduction in mortality risk. RESULTS: WTP for treatment was significantly greater than WTP for prevention, $665 and $223, respectively. Prior opinions on the relative effectiveness afforded by preventive and treatment interventions moderately influenced the WTP estimates for persons randomized to either scenario. Prior opinions on costs had no significant effect on WTP estimates for either scenario. WTP significantly increased with age and household income in the full sample but was not significantly affected by gender or educational attainment. CONCLUSIONS: The aggregated WTP responses from the prevention and treatment scenarios presented in our study would imply that treatment is more strongly preferred by society than prevention when the health context is the same and benefits of each are held constant. A better understanding is needed of the discrepancy between citizens' stated preferences for prevention (e.g., through polling) and our findings that they were willing to pay substantially more for treatment than for prevention.

Late gastrointestinal toxicity after dose-escalated conformal radiotherapy for early prostate cancer: results from the UK Medical Research Council RT01 trial (ISRCTN47772397).

PURPOSE: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects. METHODS AND MATERIALS: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Management (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires. RESULTS: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade >or=2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade >or=2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade >or=2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively. CONCLUSIONS: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.

Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial.

BACKGROUND: In men with localised prostate cancer, conformal radiotherapy (CFRT) could deliver higher doses of radiation than does standard-dose conventional radical external-beam radiotherapy, and could improve long-term efficacy, potentially at the cost of increased toxicity. We aimed to present the first analyses of effectiveness from the MRC RT01 randomised controlled trial. METHODS: The MRC RT01 trial included 843 men with localised prostate cancer who were randomly assigned to standard-dose CFRT or escalated-dose CFRT, both administered with neoadjuvant androgen suppression. Primary endpoints were biochemical-progression-free survival (bPFS), freedom from local progression, metastases-free survival, overall survival, and late toxicity scores. The toxicity scores were measured with questionnaires for physicians and patients that included the Radiation Therapy Oncology Group (RTOG), the Late Effects on Normal Tissue: Subjective/Objective/Management (LENT/SOM) scales, and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI) scales. Analysis was done by intention to treat. This trial is registered at the Current Controlled Trials website http://www.controlled-trials.com/ISRCTN47772397. FINDINGS: Between January, 1998, and December, 2002, 843 men were randomly assigned to escalated-dose CFRT (n=422) or standard-dose CFRT (n=421). In the escalated group, the hazard ratio (HR) for bPFS was 0.67 (95% CI 0.53-0.85, p=0.0007). We noted 71% bPFS (108 cumulative events) and 60% bPFS (149 cumulative events) by 5 years in the escalated and standard groups, respectively. HR for clinical progression-free survival was 0.69 (0.47-1.02; p=0.064); local control was 0.65 (0.36-1.18; p=0.16); freedom from salvage androgen suppression was 0.78 (0.57-1.07; p=0.12); and metastases-free survival was 0.74 (0.47-1.18; p=0.21). HR for late bowel toxicity in the escalated group was 1.47 (1.12-1.92) according to the RTOG (grade >/=2) scale; 1.44 (1.16-1.80) according to the LENT/SOM (grade >/=2) scales; and 1.28 (1.03-1.60) according to the UCLA PCI (score >/=30) scale. 33% of the escalated and 24% of the standard group reported late bowel toxicity within 5 years of starting treatment. HR for late bladder toxicity according to the RTOG (grade >/=2) scale was 1.36 (0.90-2.06), but this finding was not supported by the LENT/SOM (grade >/=2) scales (HR 1.07 [0.90-1.29]), nor the UCLA PCI (score >/=30) scale (HR 1.05 [0.81-1.36]). INTERPRETATION: Escalated-dose CFRT with neoadjuvant androgen suppression seems clinically worthwhile in terms of bPFS, progression-free survival, and decreased use of salvage androgen suppression. This additional efficacy is offset by an increased incidence of longer term adverse events.

The assessment of patient life-expectancy: how accurate are urologists and oncologists?

OBJECTIVE: To assess the degree of accuracy, precision and consistency with which consultant urologists, oncologists and junior doctors predict a patient's 10-year life-expectancy. SUBJECTS AND METHODS: Eighteen doctors of varying seniority independently examined 70 patient case scenarios containing detailed medical histories; 13 of these cases were duplicate scenarios. Bland-Altman analyses were used to compare doctors' estimates of the probability of each hypothetical patient surviving 10 years with that calculated using actuarial methods. Intra- and interdoctor reliability were also assessed. RESULTS: Compared with actuarial estimates, doctors underestimated the 10-year survival probability by an overall mean of 10.8% (95% confidence interval, 10.1-11.5%). The 18 individual doctors ranged from a mean underestimation of 33.2% to a mean overestimation of 3.9%. Variation around these means was considerable for each doctor, the standard deviations being 14.5-20.9%. Inter-doctor reliability was 0.58, while overall intra-doctor reliability was 0.74, but for individual doctors was 0.31-0.94. Junior doctors were less accurate in their predictions than the senior doctors. Five doctors tended to overestimate where life-expectancy was poor and underestimate where it was good. CONCLUSIONS: Doctors were poor at predicting 10-year survival, tending to underestimate when compared with actuarial estimates. There was also substantial variability both within and between doctors. The inaccuracy, imprecision and inconsistency amongst the doctors in assessing patient life-expectancy is an important finding and has significant implications for managing patients. Many patients may be denied treatment after a pessimistic assessment of life-expectancy and (less commonly) some may inappropriately be offered treatment after an optimistic assessment. The particular inaccuracy in junior doctors compared with their senior colleagues also highlights the need for training. The development of a tool to assist in both training and clinical practice has the potential to improve doctors' decision-making and patient care.

A revised economic analysis of restrictions on the use of cell phones while driving.

Evidence that cell phone use while driving increases the risk of being involved in a motor vehicle crash has led policymakers to consider prohibitions on this practice. However, while restrictions would reduce property loss, injuries, and fatalities, consumers would lose the convenience of using these devices while driving. Quantifying the risks and benefits associated with cell phone use while driving is complicated by substantial uncertainty in the estimates of several important inputs, including the extent to which cell phone use increases a driver's risk of being involved in a crash, the amount of time drivers spend using cell phones (and hence their aggregate contribution to crashes, injuries, and fatalities), and the incremental value to users of being able to make calls while driving. Two prominent studies that have investigated cell phone use while driving have concluded that the practice should not be banned. One finds that the benefits of calls made while driving substantially exceed their costs while the other finds that other interventions could reduce motor vehicle injuries and fatalities (measured in terms of quality adjusted life years) at a lower cost. Another issue is that cell phone use imposes increased (involuntary) risks on other roadway users. This article revises the assumptions used in the two previous analyses to make them consistent and updates them using recent data. The result is a best estimate of zero for the net benefit of cell phone use while driving, a finding that differs substantially from the previous study. Our revised cost-effectiveness estimate for cell phone use while driving moves in the other direction, finding that the cost per quality adjusted life year increases modestly compared to the previous estimate. Both estimates are very uncertain.