Determinants of Bone-Modifying Agent Prescribing for Metastatic Castration-Resistant Prostate Cancer in a National Health Care Delivery System.

PURPOSE: Despite guidelines recommending bone-modifying agents (BMAs) to decrease skeletal-related events (SREs) in men with metastatic castration-resistant prostate cancer (mCRPC), BMAs are underutilized. In this retrospective cohort study, we report the factors associated with BMA use in a national health care delivery system. METHODS: We used the Veterans Affairs Corporate Data Warehouse to identify men with mCRPC between 2010 and 2017. BMA prescribing frequency was evaluated, and the association between patient- and disease-specific factors with BMA use was assessed using multivariable logistic regression. RESULTS: Among 3,980 men identified with mCRPC (mean age 73.5 years, 29% Black), 47% received a BMA; median time to BMA from start of mCRPC treatment was 102 days. Factors associated with BMA use included previous BMA use (adjusted odds ratio [aOR], 7.81 [95% CI, 6.48 to 9.47]), diagnosis code for bone metastases (aOR, 1.26 [95% CI, 1.08 to 1.46]), and concomitant corticosteroid use (aOR, 1.53 [95% CI, 1.29 to 1.82]). Decreased BMA use was associated with advancing age (aOR, 0.85 per 10 years [95% CI, 0.78 to 0.92]), Charlson comorbidity index ≥2 (aOR, 0.76 [95% CI, 0.63 to 0.93]), Black race (aOR, 0.83 [95% CI, 0.70 to 0.98]), and decreased estimated glomerular filtration rate (eGFR; aOR, 0.19 [95% CI, 0.11 to 0.32] for eGFR 0-29 mL/minutes; aOR, 0.76 [95% CI, 0.64 to 0.91] for 30-59 mL/minutes). CONCLUSION: Patients who are older, Black, or have more comorbidities are less likely to receive guideline concordant care to prevent SREs. These observations highlight the unique challenges of caring for patients with mCRPC and the need for future studies to increase BMA use in these populations.

Characterization of ion release from a novel biomaterial, Molybdenum-47.5Rhenium, in physiologic environments.

BACKGROUND CONTEXT: Metals from spinal implants are released into surrounding tissues by various mechanisms. Metal ion release has been associated with clinical implant failure, osteolysis, and remote site accumulation with adverse events. Significant corrosion and associated metal ion release has been described with currently used spinal implant alloys. A novel metal alloy, Molybdenum-47.5Rhenium alloy (MoRe®), was approved for use in medical implants in 2019 by the FDA. PURPOSE: To evaluate the metal ion release profile of MoRe alloy after immersion in both a stable physiologic, as well as in an inflammatory environment. STUDY DESIGN: In vitro study. METHODS: The ion release profile of the MoRe alloy was comprehensively evaluated in-vitro after prolonged immersion in physiologic and inflammatory environments. Ion concentration analyses were then conducted using inductively coupled plasma-mass spectrometry (ICP-MS) methods. Comparative testing of titanium (Ti-6Al-4V) and cobalt chromium (Co-28Cr-6Mo) was also performed. RESULTS: Under baseline physiologic conditions, the MoRe alloy demonstrates very low molybdenum and rhenium ion release rates throughout the 30-day test period. During the first time interval (day 0-1), low levels of molybdenum and rhenium ions are detected (<0.3 µg/cm2 day) followed by a rapid reduction in the ion release rates to <0.05 µg/cm2 day during the second time interval (days 1-3) followed by a further reduction to very low steady-state rates <0.01 µg/cm2 day during the third time interval (days 3-7), which were maintained through 30 days. In the inflammatory condition (H2O2 solution), there was a transient increase in the release of molybdenum and rhenium ions, followed by a return to baseline ion release rates (days 2-4), with a further reduction to low steady-state rates of ∼0.01 µg/cm2 day (days 4-8). The measured molybdenum and rhenium ion release rates in both steady state (<0.01 µg/cm2 day), and inflammatory environments (0.01 µg/cm2 day) were far below the established FDA-permitted daily exposure (PDE) of 1,900 µg/cm2 day for molybdenum and 4,400 µg/cm2 day for rhenium. In contrast, titanium and cobalt chromium approached or exceeded their established PDE values in an inflammatory environment. CONCLUSIONS: The novel biomaterial MoRe demonstrated a lower metal ion release profile in both a physiologic and inflammatory environment and was well below the established PDE.  Comparative testing of the cobalt-chromium and titanium alloys found higher levels of ion release in the inflammatory environment that exceeded the PDE for cobalt and vanadium.

Factors influencing treatment of veterans with advanced prostate cancer.

BACKGROUND: Treatments for metastatic castration-resistant prostate cancer (CRPC) differ in toxicity, administration, and evidence. In this study, clinical and nonclinical factors associated with the first-line treatment for CRPC in a national delivery system were evaluated. METHODS: National electronic laboratory and clinical data from the Veterans Health Administration were used to identify patients with CRPC (ie, rising prostate-specific antigen [PSA] on androgen deprivation) who received abiraterone, enzalutamide, docetaxel, or ketoconazole from 2010 through 2017. It was determined whether clinical (eg, PSA) and nonclinical factors (eg, race, facility) were associated with the first-line treatment selection using multilevel, multinomial logistic regression. The average marginal effects (AMEs) were calculated of patient, disease, and facility characteristics on ketoconazole versus more appropriate CRPC therapy. RESULTS: There were 4998 patients identified with CRPC who received first-line ketoconazole, docetaxel, abiraterone, or enzalutamide. After adjustment, increasing age was associated with receipt of abiraterone (adjusted odds ratio [aOR], 1.07; 95% credible interval [CrI], 1.06-1.09) or enzalutamide (aOR, 1.10; 95% CrI, 1.08-1.11) versus docetaxel. Greater preexisting comorbidity was associated with enzalutamide versus abiraterone (aOR, 1.53; 95% CrI, 1.23-1.91). Patients with higher PSA values at the start of treatment were more likely to receive docetaxel than oral agents and less likely to receive ketoconazole than other oral agents. African American men were more likely to receive ketoconazole than abiraterone, enzalutamide, or docetaxel (AME, 2.8%; 95% CI, 0.7%-4.9%). This effect was attenuated when adjusting for facility characteristics (AME, 1.9%; 95% CI, -0.4% to 4.1%). CONCLUSIONS: Clinical factors had an expected effect on the first-line treatment selection. Race may be associated with the receipt of a guideline-discordant first-line treatment.

Pulmonary Artery Pressure-Guided Management of Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: Despite increased use of guideline-directed medical therapy (GDMT), some patients with heart failure and reduced ejection fraction (HFrEF) remain at high risk for hospitalization and mortality. Remote monitoring of pulmonary artery (PA) pressures provides clinicians with actionable information to help further optimize medications and improve outcomes. OBJECTIVES: CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients trial) analyzed PA pressure-guided heart failure (HF) management in patients with HFrEF based on their ability to tolerate GDMT. METHODS: CHAMPION enrolled 550 patients with chronic HF regardless of left ventricular ejection fraction. A pre-specified sub-group analysis compared HF hospitalization and mortality rates between treatment and control groups in HFrEF patients (left ventricular ejection fraction ≤40%). Post hoc analyses in patients who tolerated GDMT were also performed. Hospitalizations and mortality were assessed using Andersen-Gill and Cox proportional hazards models. RESULTS: In 456 patients with HFrEF, HF hospitalization rates were 28% lower in the treatment group than in the control group (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.59 to 0.88; p = 0.0013), with a strong trend for 32% lower mortality (HR: 0.68; 95% CI: 0.45 to 1.02; p = 0.06). A 445-patient subset received at least 1 GDMT (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, or beta-blocker) at baseline; these patients had 33% lower HF hospitalization rates (HR: 0.67; 95% CI: 0.54 to 0.82; p = 0.0002) and 47% lower mortality (HR: 0.63; 95% CI: 0.41 to 0.96, p = 0.0293) than controls. Compared with controls, patients receiving both components of optimal GDMT (n = 337) had 43% lower HF hospitalizations (HR: 0.57; 95% CI: 0.45 to 0.74; p < 0.0001) and 57% lower mortality (HR: 0.43; 95% CI: 0.24 to 0.76; p = 0.0026). CONCLUSIONS: PA pressure-guided HF management reduces morbidity and mortality in patients with HFrEF on GDMT, underscoring the important synergy of addressing hemodynamic and neurohormonal targets of HF therapy. (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients [CHAMPION]; NCT00531661).

Implementation and Clinical Utility of an Integrated Academic-Community Regional Molecular Tumor Board.

PURPOSE: Precision oncology develops and implements evidence-based personalized therapies that are based on specific genetic targets within each tumor. However, a major challenge that remains is the provision of a standardized, up-to-date, and evidenced-based precision medicine initiative across a geographic region. MATERIALS AND METHODS: We developed a statewide molecular tumor board that integrates academic and community oncology practices. The Precision Medicine Molecular Tumor Board (PMMTB) has three components: a biweekly Web-based teleconference tumor board meeting provided as a free clinical service, an observational research registry, and a monthly journal club to establish and revise evidence-based guidelines for off-label therapies. The PMMTB allows for flexible and rapid implementation of treatment, uniformity in practice, and the ability to track outcomes. RESULTS: We describe the implementation of the PMMTB and its first year of activity. Seventy-seven patient cases were presented, 48 were enrolled in a registry, and 38 had recommendations and clinical follow-up. The 38 subjects had diverse solid tumors (lung, 45%; GI, 21%; breast, 13%; other, 21%). Of these subjects, targeted therapy was recommended for 32 (84%). Clinical trials were identified for 24 subjects (63%), and nontrial targeted medicines for 16 (42%). Nine subjects (28%) received recommended therapy with a response rate of 17% (one of six) and a clinical benefit rate (partial response + stable disease) of 38% (three of eight). Although clinical trials often were identified, patients rarely enrolled. CONCLUSION: The PMMTB provides a model for a regional molecular tumor board with clinical utility. This work highlights the need for outcome registries and improved access to clinical trials to pragmatically implement precision oncology.

Pulmonary Artery Pressure-Guided Heart Failure Management Reduces 30-Day Readmissions.

BACKGROUND: This study examines the impact of pulmonary artery pressure-guided heart failure (HF) care on 30-day readmissions in Medicare-eligible patients. METHODS AND RESULTS: The CardioMicroelectromechanical system (CardioMEMS) Heart Sensor Allows Monitoring of Pressures to Improve Outcomes in New York Heart Association Class III Heart Failure Patients (CHAMPION) Trial included 550 patients implanted with a permanent MEMS-based pressure sensor in the pulmonary artery. Subjects were randomized to a treatment group (uploaded pressures were made available to investigators) or a control group (uploaded pressures were not made available to investigators). This analysis focuses on the 245 Medicare-eligible subjects for whom compliance with daily transmissions was 93% compared with 88% for the overall population. Medications were changed more often in the treatment group using pressure information compared with the control group using symptoms and daily weights alone. During the 515 days follow-up after implant, the overall rate of HF hospitalizations was 49% lower in the treatment group (60 HF hospitalizations, 0.34 events/patient-year) compared with control (117 HF hospitalizations, 0.67 events/patient-year; hazard ratio 0.51, 95% confidence interval 0.37-0.70; P<0.0001). Of the 177 HF hospitalizations, 155 qualified as an index HF hospitalization. All-cause 30-day readmissions were 58% lower in the treatment group (0.07 events/patient-year) compared with 0.18 events/patient-year in the control group (hazard ratio 0.42, 95% confidence interval 0.22-0.80; P=0.0080). CONCLUSIONS: Pulmonary artery pressure-guided HF management in Medicare-eligible patients led to a 49% reduction in total HF hospitalizations and a 58% reduction in all-cause 30-day readmissions. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00531661.

Interventions Linked to Decreased Heart Failure Hospitalizations During Ambulatory Pulmonary Artery Pressure Monitoring.

OBJECTIVES: This study sought to analyze medical therapy data from the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in Class III Heart Failure) trial to determine which interventions were linked to decreases in heart failure (HF) hospitalizations during ambulatory pulmonary artery (PA) pressure-guided management. BACKGROUND: Elevated cardiac filling pressures, which increase the risk of hospitalizations and mortality, can be detected using an ambulatory PA pressure monitoring system before onset of symptomatic congestion allowing earlier intervention to prevent HF hospitalizations. METHODS: The CHAMPION trial was a randomized, controlled, single-blind study of 550 patients with New York Heart Association functional class III HF with a HF hospitalization in the prior year. All patients undergoing implantation of the ambulatory PA pressure monitoring system were randomized to the active monitoring group (PA pressure-guided HF management plus standard of care) or to the blind therapy group (HF management by standard clinical assessment), and followed for a minimum of 6 months. Medical therapy data were compared between groups to understand what interventions produced the significant reduction in HF hospitalizations in the active monitoring group. RESULTS: Both groups had similar baseline medical therapy. After 6 months, the active monitoring group experienced a higher frequency of medications adjustments; significant increases in the doses of diuretics, vasodilators, and neurohormonal antagonists; targeted intensification of diuretics and vasodilators in patients with higher PA pressures; and preservation of renal function despite diuretic intensification. CONCLUSIONS: Incorporation of a PA pressure-guided treatment algorithm to decrease filling pressures led to targeted changes, particularly in diuretics and vasodilators, and was more effective in reducing HF hospitalizations than management of patient clinical signs or symptoms alone.

Sustained efficacy of pulmonary artery pressure to guide adjustment of chronic heart failure therapy: complete follow-up results from the CHAMPION randomised trial.

BACKGROUND: In the CHAMPION trial, significant reductions in admissions to hospital for heart failure were seen after 6 months of pulmonary artery pressure guided management compared with usual care. We examine the extended efficacy of this strategy over 18 months of randomised follow-up and the clinical effect of open access to pressure information for an additional 13 months in patients formerly in the control group. METHODS: The CHAMPION trial was a prospective, parallel, single-blinded, multicentre study that enrolled participants with New York Heart Association (NYHA) Class III heart failure symptoms and a previous admission to hospital. Patients were randomly assigned (1:1) by centre in block sizes of four by a secure validated computerised randomisation system to either the treatment group, in which daily uploaded pulmonary artery pressures were used to guide medical therapy, or to the control group, in which daily uploaded pressures were not made available to investigators. Patients in the control group received all standard medical, device, and disease management strategies available. Patients then remained masked in their randomised study group until the last patient enrolled completed at least 6 months of study follow-up (randomised access period) for an average of 18 months. During the randomised access period, patients in the treatment group were managed with pulmonary artery pressure and patients in the control group had usual care only. At the conclusion of randomised access, investigators had access to pulmonary artery pressure for all patients (open access period) averaging 13 months of follow-up. The primary outcome was the rate of hospital admissions between the treatment group and control group in both the randomised access and open access periods. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661. FINDINGS: Between Sept 6, 2007, and Oct 7, 2009, 550 patients were randomly assigned to either the treatment group (n=270) or to the control group (n=280). 347 patients (177 in the former treatment group and 170 in the former control group) completed the randomised access period in August, 2010, and transitioned to the open access period which ended April 30, 2012. Over the randomised access period, rates of admissions to hospital for heart failure were reduced in the treatment group by 33% (hazard ratio [HR] 0·67 [95% CI 0·55-0·80]; p<0·0001) compared with the control group. After pulmonary artery pressure information became available to guide therapy during open access (mean 13 months), rates of admissions to hospital for heart failure in the former control group were reduced by 48% (HR 0·52 [95% CI 0·40-0·69]; p<0·0001) compared with rates of admissions in the control group during randomised access. Eight (1%) device-related or system related complications and seven (1%) procedure-related adverse events were reported. INTERPRETATION: Management of NYHA Class III heart failure based on home transmission of pulmonary artery pressure with an implanted pressure sensor has significant long-term benefit in lowering hospital admission rates for heart failure. FUNDING: St Jude Medical Inc.

Limitations of right heart catheterization in the diagnosis and risk stratification of patients with pulmonary hypertension related to left heart disease: insights from a wireless pulmonary artery pressure monitoring system.

BACKGROUND: Although right heart catheterization (RHC) remains the gold standard for assessment of hemodynamics in patients with known or suspected pulmonary hypertension (PH), there are significant limitations to this type of assessment. The current study evaluates the limitations of RHC in the diagnosis of left heart-related PH (World Health Organization group II) among patients enrolled in the CHAMPION trial and discusses insights into patient risk from home implantable hemodynamic monitor (IHM) data that were not identified at the time of the RHC procedure. METHODS: The CHAMPION trial enrolled 550 New York Heart Association functional class III patients who had been hospitalized for heart failure (HF) in the previous year, regardless of left ventricular ejection fraction or etiology. Hemodynamic data obtained during baseline RHC were compared with IHM data obtained during the first week of home readings. HF hospitalization rates and mortality were analyzed to assess patient risk. RESULTS: The study population for this retrospective analysis comprised 537 patients with available IHM data. For 320 patients in the PHRHC group, home IHM data confirmed the RHC findings with similar mean pulmonary artery pressures obtained from both methods (36 mm Hg vs 36 mm Hg, p = 0.5066). However, of the 217 patients in the No PHRHC group, 106 patients (48.8%) exhibited PH based on the home IHM data (PHIHM group). The remaining 111 patients (51.2%) in the No PHRHC group had no evidence of PH on the IHM data (No PHIHM group). Patients in the No PHRHC/PHIHM group had significantly higher mean PA pressures on IHM than patients in the No PHRHC/No PHIHM group (31 mm Hg vs 18 mm Hg, p < 0.0001). Patients in the No PHRHC/No PHIHM group had significantly lower HF hospitalization rates than patients in the No PHRHC/PHIHM group (0.25 vs 0.49, incidence rate ratio = 0.51, 95% confidence interval = 0.33-0.77, p = 0.0007). CONCLUSIONS: Using only RHC, World Health Organization group II PH may be significantly under-diagnosed. In patients with left-sided HF and resting mean PA pressure ≤25 mm Hg during RHC, more frequent PA pressure monitoring using an IHM device can provide additional data for improved diagnosis and patient risk stratification compared with a single RHC alone.

Heart failure and respiratory hospitalizations are reduced in patients with heart failure and chronic obstructive pulmonary disease with the use of an implantable pulmonary artery pressure monitoring device.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with heart failure (HF). Elevated pulmonary arterial (PA) pressure can be seen in both conditions and has been shown to predict morbidity and mortality. METHODS AND RESULTS: A total of 550 subjects with New York Heart Association functional class III HF were randomly assigned to the treatment (n = 270) and control (n = 280) groups in the CHAMPION Trial. Physicians had access to the PA pressure measurements in the treatment group only, in which HF therapy was used to lower the elevated pressures. HF and respiratory hospitalizations were compared in both groups. A total of 187 subjects met criteria for classification into the COPD subgroup. In the entire cohort, the treatment group had a 37% reduction in HF hospitalization rates (P < .0001) and a 49% reduction in respiratory hospitalization rates (P = .0061). In the COPD subgroup, the treatment group had a 41% reduction in HF hospitalization rates (P = .0009) and a 62% reduction in respiratory hospitalization rates (P = .0023). The rate of respiratory hospitalizations in subjects without COPD was not statistically different (P = .76). CONCLUSIONS: HF management incorporating hemodynamic information from an implantable PA pressure monitor significantly reduces HF and respiratory hospitalizations in HF subjects with comorbid COPD compared with standard care.

Pulmonary hypertension related to left heart disease: insight from a wireless implantable hemodynamic monitor.

BACKGROUND: Pulmonary hypertension (PH) associated with left heart disease (World Health Organization [WHO] Group II) has previously been linked with significant morbidity and mortality. However, there are currently no approved therapies or hemodynamic monitoring systems to improve outcomes in WHO Group II PH. METHODS: We conducted a retrospective analysis of the CHAMPION trial of an implantable hemodynamic monitor (IHM) in 550 New York Heart Association (NYHA) Functional Class III HF patients, regardless of left ventricular ejection fraction (LVEF) or heart failure (HF) etiology. We evaluated clinical variables, changes in medical therapy, HF hospitalization rates and survival in patients with and without WHO Group II PH. RESULTS: Data were obtained for 314 patients (59%) who had WHO Group II PH. Patients without PH were at significantly lower risk for mortality than PH patients (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.19 to 0.52, p < 0.0001). PH patients had higher HF hospitalization rates than non-PH patients (0.77/year vs 0.37/year; HR 0.49, 95% CI 0.39 to 0.61, p < 0.001). In patients with and without PH, ongoing knowledge of hemodynamic data resulted in a reduction in HF hospitalization for PH patients (HR 0.64, 95% CI 0.51 to 0.81, p = 0.002) and for non-PH patients (HR 0.60, 95% CI 0.41 to 0.89, p = 0.01). Among PH patients, there was a reduction in the composite end-point of death and HF hospitalization with ongoing knowledge of hemodynamics (HR 0.74, 95% CI 0.55 to 0.99, p = 0.04), but no difference in survival (HR 0.78, 95% CI 0.50 to 1.22, p = 0.28). CONCLUSIONS: WHO Group II PH is prevalent and identifies HF patients at risk for adverse outcomes. Ongoing knowledge of hemodynamic variables may allow for more effective treatment strategies to reduce the morbidity of this disease.

Consequences of CO2 solubility for hydrate formation from carbon dioxide containing water and other impurities.

Deciding on the upper bound of water content permissible in a stream of dense carbon dioxide under pipeline transport conditions without facing the risks of hydrate formation is a complex issue. In this work, we outline and analyze ten primary routes of hydrate formation inside a rusty pipeline, with hydrogen sulfide, methane, argon, and nitrogen as additional impurities. A comprehensive treatment of equilibrium absolute thermodynamics as applied to multiple hydrate phase transitions is provided. We also discuss in detail the implications of the Gibbs phase rule that make it necessary to consider non-equilibrium thermodynamics. The analysis of hydrate formation risk has been revised for the dominant routes, including the one traditionally considered in industrial practice and hydrate calculators. The application of absolute thermodynamics with parameters derived from atomistic simulations leads to several important conclusions regarding the impact of hydrogen sulfide. When present at studied concentrations below 5 mol%, the presence of hydrogen sulfide will only support the carbon-dioxide-dominated hydrate formation on the phase interface between liquid water and hydrate formers entering from the carbon dioxide phase. This is in contrast to a homogeneous hydrate nucleation and growth inside the aqueous solution bulk. Our case studies indicate that hydrogen sulfide at higher than 0.1 mol% concentration in carbon dioxide can lead to growth of multiple hydrate phases immediately adjacent to the adsorbed water layers. We conclude that hydrate formation via water adsorption on rusty pipeline walls will be the dominant contributor to the hydrate formation risk, with initial concentration of hydrogen sulfide being the critical factor.

Can hydrate form in carbon dioxide from dissolved water?

Transport of carbon dioxide in offshore pipelines involves high pressures and low temperatures, which may lead to formation of hydrate from the residual dissolved water and carbon dioxide. While thermodynamics is able to tell us whether the hydrate phase will be stable, the question of whether its formation will actually occur under given pipeline conditions does not have a straightforward answer. In this work, we have made use of water properties obtained from molecular simulations to examine the thermodynamics of hydrate formation from water dissolved in carbon dioxide. This paper proposes a method that allows estimation of absolute thermodynamic properties and thus makes it possible to compare free energy changes due to several possible phase transitions and determine the most probable transition. This information can be used directly to choose the optimum hydrate prevention strategy. We have found that hydrate formation from a carbon dioxide solution will be thermodynamically viable at water concentration exceeding a certain level; a conclusion also supported by several previous studies. We have also extended the quantitative analysis of the thermodynamics and the kinetics of formation through a modified version of phase field theory (PFT). The work presents the way to obtain parameters required for the practical implementation of the PFT in the case of hydrate formation, as well as outlines the estimation of thermodynamic properties for systems unable to reach true equilibrium.

The "déjà vu effect:" evaluation of United States medical device legislation, regulation, and the Food and Drug Administration's contentious 510(k) program.

With the Medical Device Amendments of 1976, Congress granted FDA authority to regulate medical devices by implementing a risk-based regulatory framework. Several years prior to this legislation, the Cooper Committee reviewed the medical device regulatory landscape and uncovered weaknesses that could be detrimental to public health. However, only after several high-profile incidents involving unsafe medical devices did Congress respond with strong legislation. Since 1976, additional medical device legislative revisions have been enacted to address deficiencies highlighted by various groups representing Congress, FDA, and industry. A repetitive conclusion from these groups has been that the 510(k) program is incapable of serving as a premarket evaluation of safety and effectiveness under the existing statutory framework. However, these legislative revisions did not change the statutory framework despite these repeated findings. In 2009, CDRH convened separate groups to again review the 510(k) program. While more comprehensive than previous initiatives, the observed deficiencies and the proposed recommendations are remarkably similar to those identified by their predecessors. This cyclical review of the medical device regulatory landscape whereby the same observations and recommendations are repeated yet the output of such review does not yield major legislative revision of the existing statutory framework can be described as the "déjà vu effect." This will continue unless Congress enacts legislation that implements a new statutory framework with a different standard other than substantial equivalence. In the past, Congress has implemented major legislation only after a public health crisis. Hopefully this will not be the driving force in the future.

CHAMPION trial rationale and design: the long-term safety and clinical efficacy of a wireless pulmonary artery pressure monitoring system.

BACKGROUND: Decompensated heart failure (HF) is associated with unacceptable morbidity and mortality risks. Recent implantable technology advancements allow frequent filling pressure monitoring and provide insight into HF pathophysiology and a new tool for HF management. METHODS: The CHAMPION trial is a prospective, multicenter, randomized, single-blind clinical trial testing the hypothesis that HF management guided by frequently assessed pulmonary artery pressures is superior to traditional methods. A total of 550 subjects with New York Heart Association (NYHA) functional class III HF were enrolled at 64 sites in the United States. All subjects received the CardioMEMS HF sensor as a permanent pulmonary artery implant and were randomized to the treatment or the control group before discharge. The treatment group received traditional HF management guided by hemodynamic information from the sensor. The control group received traditional HF disease management. Safety endpoints include freedom from device/system-related complications and freedom from HF sensor failure at 6 months. The efficacy endpoint is a reduction in the rate of HF-related hospitalizations in the treatment group versus the control group at 6 months. CONCLUSIONS: The CHAMPION trial will investigate the safety and clinical efficacy of the CardioMEMS hemodynamic monitoring system and may establish this management strategy as a new paradigm for the medical management of patients with symptomatic HF.