Also endorses new anti-harassment protocol and will weigh partnership with TIME'S UP Healthcare.
This article was first published on Tuesday, June 11, 2019, in MedPage Today.
By Shannon Firth, Washington Correspondent, MedPage Today June 11, 2019
CHICAGO -- New policies aimed at curbing gender bias in medical research were approved during the American Medical Association House of Delegate meeting on Tuesday.
Before auditions were blinded, there was a vast gender imbalance among musicians in symphony orchestras, said Smitha Arekapudi, MD, an alternate delegate for the Illinois State Medical Association, during a committee discussion prior to the resolution's endorsement.
Once musicians began performing behind a screen and even removing their shoes -- presumably to prevent women's lighter footfalls or their high heels from suggesting their gender -- the percentage of women hired by symphonies shot up, Arekapudi said.
Harvard researchers published their findings of this type of intervention in the American Economic Review in 2000, noting that the introduction of "blind auditions" had "significantly reduced gender-based hiring." More specifically, the mechanism may have accounted for 25% of the increase in the proportion of women in symphony orchestras.
In order for women in medical research to level the playing field with men, with whom they compete for space in medical journals and for research dollars, the process needs to be similarly blinded, said Arekapudi.
Multiples studies have shown that among grant proposals in the peer-review process, those written by women are often scored lower than those by men. Other studies show that male job applicants in the basic sciences are seen as superior and deserving of higher pay, even when the only difference in the application materials submitted are names, Arekapudi continued.
"For these reasons, we ask the AMA to advocate for the establishment of best practices that remove gender bias" in the grant proposal process, and the process of submissions to peer-reviewed journals to include "removing names and gender identity from applications during review processes," she said.
David Rosman, MD, a delegate from the Massachusetts Medical Society, speaking on behalf of the New England delegation, said the change would decrease implicit bias, not only against women but other racial minorities as well.
However, Samuel Wong, MD, a delegate of the Young Physicians Section, expressed concern that removing a name entirely could minimize the importance of an individual's "established research background" and his or her publication history -- a critical determinant in funding decisions. He recommended minimizing, but not eliminating, gender information instead.
Arekapudi countered that even after blinding names, it would still be possible to evaluate a candidate's experience and achievements.
"There are ways to score previous publications, experience, and assess those things. This resolution really calls for figuring out what those best practices are," she said.
The resolution passed undisputed by any further debate on the House floor on Tuesday afternoon.
Agency seeks input on possible approaches to discourage high-dose prescribing.
This article was first published on Monday, June 10, 2019, in MedPage Today.
By Judy George, Senior Staff Writer, MedPage Today.
FDA advisors will meet Tuesday and Wednesday to address high doses of opioids in outpatient settings, suggesting that the agency believes dosing strengths of approved products represent a lever it can use to discourage overprescribing.
On Tuesday and Wednesday, members of the FDA's Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesia Drug Products Advisory Committee will meet to hear from experts and the public about the clinical utility and safety concerns associated with outpatients who use higher ranges of opioid doses, both higher dosage strength products and higher daily doses.
After more than a dozen presentations by clinicians, patients, and experts, the advisory committee will discuss:
The role of higher daily doses and higher dosage strength products in pain management
The risks of misuse, abuse, addiction, and overdose attributable to higher doses and higher dosage strength products versus lower doses and products
Potential effects if the FDA were to take regulatory action to reduce prescribing and use of higher dosage strength opioids
Whether there's value in the FDA taking new regulatory actions to reduce prescribing and use of higher dosage strength opioids
The FDA increasingly is moving toward a systems-based approach to assessing potential regulatory actions that may help address the opioid crisis, noted Judy Staffa, PhD, RPh, associate director for the Public Health Initiatives Office of Surveillance and Epidemiology at the FDA's Center for Drug Evaluation and Research (CDER), in anoverview published before the meeting.
"This means considering the decisions and behaviors of multiple stakeholders: healthcare providers, patients, communities, insurers and others," she wrote. "It also means fully evaluating the interrelated set of factors that can affect opioid analgesic use, and impact opioid misuse, abuse, addiction, overdose and death."
The agency frequently hears from patients and providers that higher-dose opioid analgesics are necessary to manage pain for some patients, but also is aware of increasing public concern about the risks these products pose to patients and others in the community, Staffa observed. "There is a strong need to bring together the community of stakeholders to consider the collective scientific understanding of the issues relating to higher daily doses and higher dosage strength opioid analgesic products and potential strategies to reduce risks to patient and public health," she noted.
Opioid products present unique risks and benefits, but risks associated with inadequate pain management also must be addressed, Ning Hu, MD, medical officer of CDER's Division of Anesthesia, Analgesia, and Addiction Products, pointed out in a memo included in the FDA briefing materials.
Nearly 12% of Veterans Health Administration patients whose clinicians discontinued long-term opioids for chronic pain had documented suicidal ideation and suicidal self-directed violence within a year, she observed. Rapid, forced opioid tapering can destabilize chronic pain patients, precipitating severe opioid withdrawal with worsening pain and profound loss of function, and some patients may seek relief from illicit drugs, she added.
"In support of the idea that there should be absolute limits on the total daily dose of opioid analgesics, many have inappropriately turned to the CDC Guideline for Prescribing Opioids for Chronic Pain -- United States, 2016," Hu wrote. "However, the guidelines were misinterpreted and misapplied, contributing to substantial harms to patients, particularly patients with chronic pain who were forced to taper their previously stable opioid doses to lower doses, or who were forced to discontinue their opioids through forced tapers or patient abandonment."
The FDA briefing materials also included a review from the agency's Division of Epidemiology, which concluded that while claims-based studies suggest an association between higher prescribed daily opioid doses and increased risks of abuse and addiction, it "remains unclear whether the higher dose plays a causal role in the development of opioid addiction." The reviewers also noted that epidemiologic evidence suggests a higher daily opioid dose likely contributes causally to increased overdose risk, but is only one of several factors.
The FDA has established a docket for public comment on this meeting, which will be open until June 30. To date, about 1,000 comments have been registered.
The agency will not issue a final determination until input from the advisory committee process has been considered and all reviews have been finalized. That determination may be affected by issues not discussed at the advisory committee meeting.
White-coat hypertension left untreated is associated with death and cardiovascular events, but out-of-office blood pressure (BP) still should be monitored in such patients, authors of a meta-analysis argued.
Across 27 observational studies with at least 3 years of follow-up, untreated white-coat hypertension carried a 36% increased risk for cardiovascular (CV) events, a 33% increased risk of all-cause mortality, and a 2.09-fold cardiovascular mortality risk; all statistically significant.
The white-coat effect among antihypertensive-treated patients held no significant risk of those outcomes, Jordana Cohen, MD, of the University of Pennsylvania in Philadelphia, and colleagues reported in the Annals of Internal Medicine.
While the 2017 national blood pressureguidelines and other recommendations have advocated out-of-office BP monitoring, real-world practice has been slow to adopt it, Cohen's group noted.
"A major barrier is skepticism over the utility of screening for isolated office hypertension ... due to unclear evidence," they wrote.
The reason for the wildly discrepant findings in prior studies might be explained by design, as sensitivity analyses of the meta-analysis showed, Cohen's group suggested.
White-coat hypertension only carried CV disease (CVD) risk in studies with an older mean age (at least 55) and higher risk features (chronic kidney disease, diabetes, or history of CVD). The association was also stronger in studies with longer follow-up (≥5 years).
"Therefore, the increased CVD risk associated with WCH [white coat hypertension] may be present only among older persons who have high CVD risk," noted an accompanying editorial by Daichi Shimbo, MD of Columbia University Medical Center in New York City, and Paul Muntner, PhD, of the University of Alabama at Birmingham.
They argued that the analysis supports U.S. and European guidelines recommending out-of-office BP monitoring to screen for white-coat effects.
For adults taking antihypertensive medication, "out-of-office monitoring seems warranted to prevent intensification of antihypertensive treatment," Shimbo and Muntner wrote. "For adults not taking antihypertensive medication ... out-of-office BP monitoring is useful for distinguishing between WCH and sustained hypertension among persons with high office BP."
About Those HTN Guidelines
A separately published comparison of blood pressure guidelines noted the agreement between the American College of Cardiology (ACC)/American Heart Association (AHA) and the European Society of Cardiology (ESC)/European Society of Hypertension (ESH) recommendations on use of home BP and ambulatory measurement.
"[T]he only real disagreement is that the ACC/AHA guidelines maintain that all people with blood pressure >130/80 mm Hg have hypertension, and blood pressure should be lowered to <130/80 mm Hg in all," George Bakris, MD, of the University of Chicago, and colleagues wrote in the Journal of the American College of Cardiology.
"In contrast, the ESC/ESH guidelines state that hypertension is defined as >140/90 mm Hg, with the goal being a level <140/90 mm Hg for all targeting to <130/80 mm Hg only in those at high cardiovascular risk, but always considering individual tolerability of the proposed goal."
The paper concluded that the difference represents no "fundamental problem" with either guideline, "rather the disconnect between a given culture's willingness to adopt a healthy lifestyle as well as governments' and insurance companies' willingness to support physicians and health care providers to implement these changes."
However, an accompanying viewpoint by Sanjay Kaul, MD, of Cedars-Sinai Medical Center in Los Angeles, wasn't so sanguine about either guideline.
The 2017 ACC/AHA blood pressure guideline "is in reasonable compliance" with the Institute of Medicine standards; however, there's plenty left to be desired with regard to the strength of evidence used and potential conflicts of interest, he found.
Of the total recommendations in the guideline, 35% were Class II "consistent with equivocal evidence" and 40% had level of evidence (LOE) C driven by expert opinion or limited data.
"Remarkably, 37% of ACC/AHA and 49% of ESC Class I recommendations are considered LOE: C, based principally on consensus opinion," Kaul wrote.
While relationships with industry were nonexistent, three members of the guideline development group were on the leadership team of SPRINT, "which had an inordinate influence on the guideline recommendations" but had its own limitations, he pointed out.
Among Kaul's list of changes that could improve the guideline process, he suggested that guideline-relevant clinical trial leaders should only serve as advisors during external peer review.
"Some may view this as an extreme position, but this is no different than what happens with external advisors at the Food and Drug Administration Advisory Committee meetings and at other federal agencies," he wrote. "Surely, the guideline committees can find a sufficient number of individuals with required content expertise to provide unbiased input on guideline subject matter."
Cohen disclosed support from the National Heart, Lung, and Blood Institute.
Shimbo disclosed relevant relationships with Abbott Vascular, Edward Lifesciences, Medtronic, and Tryton Medical unrelated to hypertension or blood pressure measurement.
Muntner disclosed support from Amgen.
Bakris disclosed relevant relationships with Merck, Vascular Dynamics, Bayer, and Novo Nordisk; being a member of the steering committees of CREDENCE (Janssen) and CALM-2 (Vascular Dynamics); and serving as principal investigator of the FIDELIO trial (Bayer).
Kaul disclosed no relevant relationships with industry.
CHICAGO -- The struggle between maintaining patient privacy and ensuring the best possible treatment of patients was evident Sunday asAmerican Medical Association(AMA) House of Delegates members debated whether patients' drug addiction treatment records should be made more easily available.
"Why would you make an exemption for this very important, critical piece of information for a physician making a decision regarding patient care?" said Robert Wailes, MD, of Rancho Santa Fe, California, a delegate from the American Academy of Pain Medicine. "As a pain physician, I desperately need to know if a patient is on a controlled substance like methadone or buprenorphine."
"Opioid use disorder is a significant concern among women," said Marilyn Heine, MD, of Langhorne, Pennsylvania, on behalf of the AMA women physicians section."When HIPAA [the Health Insurance Portability and Accountability Act] violations are escalating and penalties [for violation] are being cut, it's even more urgent that we ensure vulnerable patients' privacy will be protected. At a time when substance use disorder patients face stigma, rampant discrimination, and potential loss of custody, housing, and employment that threatens their recovery if confidentiality is breached, we must champion their rights."
The comments came during a House of Delegates reference committee meeting; the committee was discussing several resolutions and a board report addressing whether opioid use disorder treatment records should be made accessible to both healthcare providers and law enforcement officers via databases such as a state Prescription Drug Monitoring Program (PDMP).
One resolution, introduced by a host of delegations including the American Psychiatric Association, the American Society of Addiction Medicine, and delegations from Colorado, Vermont, Washington, and Wisconsin, would require the AMA to support aligning federal regulations with HIPAA for the purposes of treatment, payment, and healthcare operations, but opposing use of substance disorder records in criminal proceedings; it would also have the AMA "support the sharing of substance use disorder patient records as required by the HIPAA Privacy Rule."
Another resolution would have the AMA "study whether the confidentiality protections of 42 CFR Part 2 outweigh the potential benefits of coordinating care with HIPAA privacy protections in the treatment of substance related disorders." The 42 CFR Part 2 regulation prohibits unauthorized disclosure of patient records except in certain circumstances.
The Board of Trustees also weighed in on the issue with a report on a resolution from the 2018 AMA meeting that would have had the AMA seek changes to require that opioid treatment programs to report to PDMPs.
"The AMA has significant privacy concerns about law enforcement and other non-healthcare entities using a PDMP because of the personal health information (PHI) contained within a PDMP," the report said. "PHI may include a patient's controlled substance prescription history, which can potentially cause someone to learn a patient is being treated for gender dysphoria, a substance use disorder, mental illness, HIV/AIDS, or other medical condition that has historically been subject to stigmatization."
"The AMA believes that an appropriate balance between law enforcement access and a patient's right to privacy occurs when law enforcement obtains a court-issued warrant or other judicially authorized access. That occurs, however, in fewer than 20 states." The report recommended that the resolution not be adopted.
Some delegates took a more moderate approach."I speak with great trepidation to voice opposition to the board report," said Lee Snook, MD, of Sacramento, California, a delegate from the American Society of Interventional Pain Physicians, who was speaking for himself.
"This horse has left the barn ... We are required to use [the PDMP] or some type of electronic prescription monitoring ... and compelled to do biological fluid analysis on our patients for whom we're prescribing controlled substances ... It's important that this should be referred back to the board for consideration in view of the inherent conflict it's creating, because as practitioners we'll have to explain why the substance is present and not in your [PDMP]."
Peter Kaufman, MD, of Bethesda, Maryland, a delegate from the American Gastroenterological Association who was speaking for himself, called the subject "a very thorny issue ... You'd definitely want to know what drugs the patient is on at any time, but on the other hand, you don't want people with a substance abuse problem to have any inhibition ... to get substance abuse treatment ... I challenge you to come up with a good solution for that," he said to the reference committee.
Another reference committee got a visit from Surgeon General Jerome Adams, MD, who came to speak in favor of giving Medicare beneficiaries better access to dental care. The surgeon general was speaking in response to a report from the AMA's Council on Medical Service, which recommended that the association "support continued opportunities to work with the ADA [American Dental Association] and other interested national organizations to improve access to dental care for Medicare beneficiaries."
The report also urged that the AMA "support initiatives to expand health services research on the effectiveness of expanded dental coverage in improving health and preventing disease in the Medicare population" as well as supporting research on the optimal dental benefit plan design. Adams noted that one of his predecessors, former Surgeon General David Satcher, MD, put out a report 20 years ago highlighting the importance of insurance coverage for oral health services.
"I'll be putting out a Surgeon General's report -- a 20-year update -- next year highlighting these issues ... I'm not in a position to advocate one way or the other [on the report] but I want to applaud the council and the House [of Delegates] for taking on this important issue because the science tells us when people are covered for critical oral health services, they're healthier, communities are healthier ... and our country is safer. One of the number one reasons people are sent home from deployment in the military is because of oral health issues."
"The Office of the Surgeon General supports oral health and supports measures to increase coverage for oral health," he added.
Physical health markers in mentally ill patients improved under 'reverse co-location' model.
This article was first published on Thursday, June 6, 2019 in MedPage Today.
By Shannon Firth, Washington Correspondent, MedPage Today.
WASHINGTON -- Adults with serious mental and physical illness who received primary care at behavioral health clinics in South Texas saw greater reductions in systolic blood pressure and HbA1c (glycated hemoglobin) levels compared with usual care in a randomized trial, according to researchers.
This treatment model for individuals with serious mental illness, called "reverse co-location" of primary care and psycho-behavioral treatment, essentially makes the community mental health clinic the patients' "medical home" for their healthcare needs.
Karen Sautter Errichetti, DrPH, MPH, of Health Resources in Action, a Boston-based nonprofit public health institute, shared the results of the study at the AcademyHealth Annual Research Meetinghere on Monday.
"This is the epicenter of heath equity work," said Errichetti, underscoring the social determinants of health -- from mental to socioeconomic and sociopolitical challenges -- faced by residents of the South Texas border region where the study was implemented.
"What was amazing was that we got a positive result," she said, in a follow-up phone interview, noting that in these types of studies it's rare to see a difference between the intervention and control groups.
"To be able to move blood pressure within 1 year in a population with severe mental health challenges is striking and notable," Errichetti told MedPage Today -- highlighting the finding that the intervention group saw a slight improvement in systolic blood pressure that was statistically significant.
"That kind of finding is not common in the literature," she added.
This is the first study, "to my knowledge," that systolic blood pressure has moved in the setting of a local mental health authority in a population that is predominantly Hispanic, she said.
When controlling baseline measures and covariates, researchers found that participants in the treatment group had greater reductions in the confirmatory outcome (reduced systolic blood pressure, β=-3.86, P=0.04) and an additional finding of reduced HbA1c (β=-0.36, P=0.001) at 12 months in comparison with control participants, according to a May 2018 final evaluation report from Tropical Texas Behavioral Health (TTBH), a local mental health authority serving 1.2 million residents of Hidalgo, Cameron, and Willacy counties in Texas.
As for the overall clinical impact, one would need to assess whether the reductions in systolic blood pressure or HbA1c moved an individual from hypertensive to pre-hypertensive or from diabetes to controlled diabetes, Errichetti said, "and we did not do those kinds of analyses."
Asked what precisely was included in the care plans that contributed to the improvements in health, Errichetti said she couldn't say. Some patients might have seen a primary care physician and been prescribed a blood pressure medication as part of a care plan, which accounted for the reduction in blood pressure, while another patient might have been prescribed a walking program during a visit with the chronic care nurse, Errichetti speculated.
"We can't disentangle what may have made the difference for that individual patient. All we can say is that co-locating primary care in a local mental health authority setting improves systolic blood pressure and A1c," Errichetti said.
The report also clarified that researchers saw "no negative intervention effects" on the confirmatory or exploratory outcomes of the study.
Errichetti worked alongside two other co-lead authors, M. Marlen Ramirez of TTBH, and Michelle Brodesky of Methodist Healthcare Ministries, to complete the study.
The randomized controlled trial was part of the Sí Texas (Social Innovation for a Healthy South Texas Evaluation) initiative, a multi-site evaluation of integrated behavioral health programs enacted by eight organizations, which was funded through a 2014 grant from the Social Innovation Fund, part of the Corporation for National and Community Service.
The study involved four behavioral health clinics, two of which tested integrated care strategies.
The core research question explored by Errichetti and her colleagues was whether adult patients with serious mental illness -- e.g., depression, schizophrenia, bipolar disorder -- who received coordinated and co-located behavioral health and primary care services would see improvements in their health and quality of life after 12 months when compared with a similarly matched group of adults who received only behavioral health services.
Study Details
Participants in the study were adults older than age 18, with a diagnosed serious and persistent mental illness who had one or more chronic conditions -- hypertension, poorly controlled diabetes, obesity, or hypercholesterolemia. Participants also needed to be residents of either Hidalgo or Cameron Counties.
The researchers excluded adults who were actively suicidal at the time of enrollment or pregnant.
Data for relevant measures was collected at baseline and at 6 and 12 months.
A total of 416 participants enrolled in the study; 249 were randomized to the treatment group, and 167 were randomized to the control group. The mean age of study participants was 41. Approximately 55% were female, and 93% were Hispanic; 31% of the participants had bipolar disorder, 46% had major depression, and 20% had schizophrenia.
The protocol for the treatment arm stipulated a minimum of two visits with a primary care clinician per patient and one visit with a dietitian or chronic care nurse. However, Errichetti explained, the study followed an intent-to-treat approach, meaning that there wasn't a required threshold of visits that participants needed to meet in order to be included in the analysis, as long as they came in to have assessments and measures taken.
The "vast majority" of participants, however, did complete the required minimum visits, she noted.
In addition to systolic blood pressure and HbA1c levels, the researchers also measured diastolic blood pressure, body mass index, cholesterol, and PHQ-9 scores.
Depression scores did not improve in the treatment arm, and there weren't any statistically significant differences between groups. The researchers also looked at "adult functioning" -- a quality-of-life indicator -- but found no statistically significant differences. (The measurement tool has not yet been validated, and so those results weren't presented at the meeting, she said.)
The primary limitation of the study is its generalizability, said Errichetti. Because the study was conducted in a population of people with serious mental illness and in a border community, generalizability is limited to populations meeting those contexts. In addition, she said, while it may be relevant to studies of other communities of color, "it really has the most-broad applicability to communities that are similar to it."
"When we're working in a setting where many social determinants are at play, we want to make sure that the interventions we design are going to work in those settings," Errichetti stated. "This [study] is going to be tremendously helpful in thinking about how to work on issues like health equity -- which is something that I think people at the border think about a lot -- and it has the potential to reduce healthcare disparities, simply by locating primary care in a trusted setting for individuals who are among the most vulnerable in the United States," she said referring to people with serious mental illness.
CHICAGO -- Minimally invasive hysterectomy conferred a significantly higher risk of cervical cancer recurrence compared with abdominal procedures, data from eight high-volume centers showed.
An unadjusted analysis showed the hazard for 5-year recurrence-free survival (RFS) more than doubled with minimally invasive surgery (MIS). Two different adjusted analyses showed even larger disparities, yielding hazard ratios (HRs) of 4.16 and 3.71, according to Shitanshu Uppal, MD, of the University of Michigan in Ann Arbor.
A propensity-matched analysis showed almost a three-fold increased risk of recurrence with MIS, he reported at the American Society of Clinical Oncology (ASCO) annual meeting.
The report continued a run of bad news for MIS hysterectomy that began in 2018 at the Society of Gynecologic Oncology (SGO) meeting, when one study showed an increased risk of recurrence with MIS, and another showed an increased mortality risk. Just last month, an analysis by the British public health service showed a fourfold spike in the survival hazard for patients who underwent MIS hysterectomy from 2013 to 2016.
"Is this a fight worth fighting?" Uppal asked. "Whether minimally invasive hysterectomy should continue or not is up for debate. If we do so, there will be some big questions on cervical cancer volume. Are we ready for centralization of care?"
"Another issue is that patients who have open surgery, and then enhanced recovery protocols, have minimal morbidity. The benefit derived from minimally invasive techniques might not be worth the risk involved," he stated.
'Belief Bias?'
The sudden influx of negative reports might have triggered a"belief bias" reaction among supporters of MIS hysterectomy, suggested ASCO invited discussant Patricia Eifel, MD, of the MD Anderson Cancer Center in Houston. She noted that MIS for cervical cancer had rapid adoption and uptake as a worldwide standard, supported by a number of positive, albeit retrospective, reviews of data.
For example, an analysis of 23 studies involving 4,205 patients showed advantages for MIS related to operative time, blood loss, hospital stay, return of normal bowel activity, transfusions, and bladder catheterization. The benefits led the authors to conclude that laparoscopic radical hysterectomy outweighs abdominal radical hysterectomy "in most essential aspects."
"[The spate of negative studies] was a shock to many surgeons. Many, many editorials were published. Efforts to explain this away and to find ways to rationalize how it might not be a knock-out punch for minimally invasive surgery," said Eifel.
"I guess [Uppal's report] is just an additional bit of evidence for belief bias: The drive to accept believable conclusions in the face of inconclusive results is very strong," she added. "Even well-substantiated conclusions may be difficult to accept if they counter belief. I think we need to look very closely at data that follows our preconceived notions to determine whether we really are accepting it because of the validity and the quality of the data, or because we want it to be true."
As the invited discussant for the SGO presentations, Uppal expressed surprise at the negative data regarding MIS. He reported findings at ASCO from an analysis that attempted to address some of the perceived shortcomings of the negative studies. Though retrospective, the data came from eight, high-volume academic centers with reputations and recognition for quality care.
Key Findings
The analysis involved 731 patients who underwent radical hysterectomy for cervical cancer from Jan. 1, 2010 through Dec. 31, 2017. Patients with preoperatively identified metastatic disease were excluded. MIS was performed in 72.1% of the cases, and 91% of the MIS cases involved robotic assistance. Eight of the 204 open abdominal procedures were converted from MIS.
Baseline characteristics had several imbalances: Fewer black patients and more Hispanic patients had open surgery; missing data on preoperative tumor size for 15.6% of the MIS group versus none of the open-surgery group; missing data on tumor grade for 13.7% of the MIS group versus 4.9% of the open group; the open-surgery patients had larger tumors at final analysis (2 vs 1.3 cm); median follow-up of 45 months for the open-surgery group versus 30.5 months for the MIS group; and missing data on lymphovascular space invasion (LVSI) for 4.2% of MIS patients versus 0.5% of the open-surgery group.
The primary outcome of the study was a 5-year recurrence rate, which was 6.9% with open surgery and 9.3% with MIS. An unadjusted analysis of RFS yielded an HR of 2.06 for the MIS group (95% CI 1.06-4.00). Investigators performed two adjusted analyses. In both analyses they controlled for comorbidities, race, body mass index, pathology grade, histology, surgical approach, adjuvant therapy, and LVSI. One analysis controlled for preoperative tumor size and the other for final tumor size.
The two analyses yielded HRs of 4.16 with inclusion of preoperative tumor size and 3.71 when tumor size on final pathology was incorporated.
From the total study population, Uppal and colleagues formed propensity-matched cohorts involving 132 patients who had abdominal surgery and 125 who had MIS. The 5-year recurrence rate was more than two times higher in the MIS group (14.4% vs 6.1%, P=0.027), which translated into an HR of 2.93. Overall survival was not significantly different between groups.
One additional analysis suggested that use of a uterine manipulator might be a contributing factor to the higher recurrence rate seen in MIS cases, said Uppal. In 31 cases performed without a manipulator, none of the patients had disease recurrence. In contrast, recurrence rates of 8.2% and 11.7% were seen with the use of intrauterine and vaginal manipulators, respectively.
Uppal disclosed no relevant relationships with industry.
WASHINGTON -- Refusal to undergo cancer surgery continues to be a problem in certain sociodemographic groups, a researcher said here.
In particular, patients were more likely to refuse surgery for breast, colon, lung, or prostate cancer if they were older, African American, and unmarried, Joseph Rapp, MPH, of the CUNY School of Public Health and Health Policy, in New York City, said at the AcademyHealth Annual Research Meeting.
"Despite progress in the field, cancer patients who are non-white, lacking health insurance, and unmarried are less likely to receive surgical intervention in cancer," Rapp said. "Recent research has identified refusal of recommended surgery as a potential reason for some of these disparities persisting, but it's relatively understudied."
In particular, "no study specifically exists on early-stage cancers, and this is important, because surgical resection in early stages ... typically confers the best survival benefits and sometimes is curative," he said.
So Rapp and his colleagues decided to assess clinical and demographic predictors of surgery refusal in certain early-stage cancers, as well as survival among those who underwent the surgery versus those who refused it. They used data from the Surveillance, Epidemiology, and End Results (SEER) database, which collects cancer incidence data from population-based cancer registries covering approximately 34.6% of the U.S. population.
They looked at breast, lung, colon, and prostate cancer cases diagnosed from 2007 through 2014, and focused on stage 1 and 2 diagnoses. Exclusion criteria included no recommendation for surgery and cases in which it was not the patient's first cancer diagnosis. After further stratifying the analysis to include only certain types of each kind of cancer, the investigators ended up with a total of 485,000 cases, more than half of which were breast cancer patients.
Possible sociodemographic predictors of surgery refusal included:
Age at diagnosis
Sex
Race/ethnicity
Marital status
Insurance status
Proximity to a metropolitan area
Possible clinical predictors included stage at diagnosis and -- for breast cancer only -- the cancer histology (tubular vs ductal).
In terms of demographics, the average age for each type of cancer patient ranged from 60.2 for breast cancer patients to 68.2 for colon cancer patients. The vast majority of patients in all four groups -- 97% to 99% -- were insured. Most of the patients were married, with a range of 54% for colon cancer patients to 75% for prostate cancer patients.
The majority of patients in each group -- ranging from 70% of colon cancer patients to 79% of lung cancer patients -- were white. Non-Hispanic black was the next most common ethnicity (9% to 13% in each group), followed by Hispanic, Rapp said.
Overall, surgery refusal was quite uncommon, but occurred most often among prostate cancer patients (3.3%), followed by lung cancer patients (2.5%), and then breast and colon cancer patients (0.35% in each group). Refusal predictors for each cancer type were similar but slightly different in their order -- for example, the biggest predictor for refusing breast cancer surgery was being uninsured (adjusted odds ratio 2.74), while for refusing colon cancer surgery, being older was the biggest predictor (adjusted OR 5.26).
In general, patients who refused surgery had worse survival outcomes than those who underwent surgery, Rapp said. Using a propensity-matched analysis, the researchers found that colon cancer patients who refused surgery had the worst outcomes -- they were nearly eight times more likely to die during the study period (adjusted hazard ratio 7.92) than their counterparts who underwent surgery. They were followed by breast cancer patients with an adjusted HR of 6.50, lung cancer patients (2.67), and prostate cancer patients (1.81).
As to why patients refuse surgical intervention, "some studies done about 10 years ago indicate there are possible misconceptions about surgical intervention, in particular within the African-American population," Rapp told MedPage Today. "That study doesn't parse out why that might be either. The only speculation I can make is that these are populations that aren't receiving adequate healthcare education."
The study's limitations included the fact that reasons for refusal were unknown, as were what type of insurance patients had and their comorbidities. Strengths included the large sample size, the focus on early-stage cancers, and the ability to use propensity score match analysis to control for selection bias.
"Future studies should probably look to investigate why patients are refusing their surgeries, and include insurance and confounder data, and possibly investigate procedures being refused," he said. "Other studies could possibly investigate whether patients are being recommended surgery at the same rate" across various groups.
Over $1 billion in sales for drug possibly without benefit.
The article was first published on Monday, June 3, 2019 inMedPage Today
By Ian Ingram, Deputy Managing Editor, MedPage Today
CHICAGO -- A year-long overall survival improvement with olaratumab (Lartruvo) in an early-phase soft-tissue sarcoma trial disappeared when the drug was tested in a larger phase III trial.
Among more than 500 doxorubicin-treated patients in ANNOUNCE, those randomized to olaratumab had a median OS of 20.4 months compared with 19.7 months for those on placebo (HR 1.05, 95% CI 0.84-1.30, P=0.69), reported William D. Tap, MD, of Memorial Sloan Kettering Cancer Center in New York City.
"The control arm had the highest overall survival rate for doxorubicin in any phase III soft-tissue sarcoma clinical trial," Tap noted during the plenary session presentation at the American Society of Clinical Oncology annual meeting.
Median OS in the large leiomyosarcoma subgroup was not significantly different either (21.6 vs 21.9 months, respectively).
Prior data from a phase Ib/II open-label trial had shown an "unprecedented" 11.8-month improvement with olaratumab over placebo for advanced soft-tissue sarcoma patients (HR 0.46, 95% CI 0.30-0.71, P=0.0003), and a 16.1-month improvement in the leiomyosarcoma group, Tap said.
"These data were highly debated and scrutinized," he noted, but said that extensive subset analyses did not reveal any bias or meaningful imbalances that could have explained the results.
Based on this data, olaratumab received accelerated approval from the FDA in 2016, which was contingent upon a confirmatory phase III trial (ANNOUNCE), and went on to receive accelerated, conditional, or full approval from regulatory agencies in more than 40 countries.
Olaratumab is a fully monoclonal antibody of immunoglobulin G class 1 that selectively binds to PDGFR-alpha. The drug demonstrated synergy with doxorubicin in sarcoma models, though its exact mechanism of action in the various types of soft-tissue sarcoma is unclear.
"Curiously, the survival in both studies seemed to be better in absence of the drug's target," noted ASCO invited discussant Jaap Verweij, MD, PhD, of Erasmus University in Rotterdam, the Netherlands. "If a drug seems to work in absence of its target, I would question the results and aim to find an explanation before embarking on a large trial."
In ANNOUNCE, exploratory analyses of PDGFR-alpha in the olaratumab group revealed an OS of 17.1 months in those with tumors expressing the target compared with 23.6 months for those whose tumors did not.
Verweij noted that toxicity in the combination arm was similar to single-agent doxorubicin, so patients exposed to olaratumab were not subjected to physical harm. Any grade adverse events in the trial were similar between the investigational and placebo groups for all-grade toxicity, grade 3/4 events, serious adverse events, treatment-emergent deaths, and treatment discontinuation.
[The] "flip side of the coin, however, for the accelerated approval is the financial burden to society," he said. "With sales on olaratumab in the third-quarter of 2018 reported to be $221 million, the total financial burden to society in the 2 years after conditional approval must have largely exceeded $1 billion, which at least in my humble opinion, seems to be a lot of expense for a drug without proven efficacy."
Being a "little bit provocative," Verweij suggested that perhaps researchers should shift their focus away from adding drugs onto doxorubicin.
"We sadly have to conclude that, after decades, doxorubicin remains the standard of care for the lump group of soft tissue sarcomas," he concluded.
Tap acknowledged that it's possible olaratumab has no activity in soft-tissue sarcomas, and that the phase Ib/II results were perhaps due to sample size, numerous histologies with disparate clinical behaviors, subsequent therapy, or even chance. It's also possible, he said, that the agent is active, and that outcomes were affected by the heterogeneity of the study population, trial design, and performance of the control arm.
From 2015 to 2016, the phase III, double-blind trial randomized 509 locally advanced or metastatic soft-tissue sarcoma patients to treatment with doxorubicin plus either olaratumab (n=258) or placebo (n=251).
The study was powered to evaluate OS in all patients as well as in the leiomyosarcoma subgroup (46.0%, with 18.5% uterine), and would be considered positive if either or both endpoints were met. Liposarcoma was the second-most common histology (17.9%), followed by pleomorphic sarcoma (12.6%). Patients with 26 other histologies comprised the remaining 23.6%.
Median patient age was 57, and roughly half had high-grade histology. The vast majority (82.9%) had metastatic disease and three-fourths had received no prior systemic therapy. Patients on olaratumab received fewer median doxorubicin infusions than the placebo group (6 vs 7), resulting in lower exposure to the cytotoxic agent (409 mg/m2 vs 483 mg/m2, respectively).
Progression-free survival was significantly worse with olaratumab in the total population. No significant differences were seen between overall response rates in either study group, but in the leiomyosarcoma subpopulation the rate of stable disease was significantly worse with olaratumab.
Tap disclosed multiple relevant relationships with industry, including Atropos Pharmaceuticals, BioAtla, Certis Oncology Solutions, Agios, Blueprint Medicines, Daiichi Sankyo, Eisai, EMD Serono, GlaxoSmithKline, Immune Design, Janssen, Lilly, Loxo, NanoCell, Novartis, and Plexxikon.
Verweij disclosed relevant relationships with OCTIMET, Basilea, Genmab, InteRNA, Novartis, Sanofi, XBiotech, Sotio, and XBiotech.
WASHINGTON -- Prior authorization requests made by physicians to Medicare Advantage plans would get a little simpler under legislation that a bipartisan group in Congress plans to introduce this week.
The "Improving Seniors' Timely Access to Care Act of 2019" sets standards for electronic requests for "prior authorization" -- pre-approval from an insurer for a particular medicine or procedure -- in the Medicare Advantage program. The bill, which is expected to be introduced Wednesday or Thursday, includes a surgical exception during the perioperative period, as well as a path for real-time decisions and protections for beneficiaries, according to congressional staff members. It also requires stakeholders to give Congress recommendations on ways to further streamline the prior authorization process.
Cosponsors of the bipartisan bill include Rep. Roger Marshall, MD (R-Kan.), Rep. Mike Kelly (R-Pa.), Rep. Ami Bera, MD (D-Calif.), and Rep. Suzan DelBene (D-Wash.). Kelly and DelBene are members of the House Ways & Means Committee, which would likely have jurisdiction over any prior authorization bill. Although the bill would apply only to Medicare Advantage plans, private insurers often follow suit once Medicare puts a particular policy in place.
The bill is not the only development happening on the prior authorization front. In May, the Committee on Operating Rules for Information Exchange (CORE), a division of the Council for Affordable Quality Healthcare (CAQH) issued operating rules to promote automation in prior authorization; today, 88% of prior authorizations are done partially or entirely manually, using phone and fax. The CORE group includes more than 130 stakeholders -- health plans, provider groups, government agencies, and standards organizations -- "and by creating those standards, it creates common expectations between plans and providers about what information needs to be exchanged, when, and how," April Todd, senior vice president of CAQH CORE, said in a phone interview.
With the standards, "we've put rules in place so that when a provider submits a request to a health plan, there are rules about information that needs to be submitted for the patient -- even standards around 'first name, last name, date of birth,' so that the health plan can find the patient in the system," Todd explained. "Often, prior authorizations are declined because the plan can't find the patient."
Another example of standardization involves the reasons a plan doesn't act on a prior authorization request. Often, "once a provider submits a request, what the plan sends back to the provider is that the request was 'pended,' or put on hold for more information," said Todd. "The provider receives the response back and does not know what to do next. We put standards around [situations in which] the plan is requesting more information -- what they need information on and what kind of documentation they need, so the provider will know 'I need to send a lab result back.'"
CORE's rules were approved by 90% of the group's participating organizations, and are available for adoption by the industry right now, Todd said. "We're also working on a certification test suite, and that will be available later this year," she added. "Certification signals to trading partners that they are compliant with the rules. For example, many health plan participants in CORE require vendors to receive certification before a contract could be put in place."
CORE expects that organizations will soon start implementing the standards, and CORE will be monitoring to see whether they are effective, according to Todd. However, "this is not the endgame in prior authorization," she said. "We're continuing to work on other components of the workflow; we're starting to do pilot projects to test ways to help providers even before they submit a prior authorization, to figure out whether one is needed."
CORE members also are awaiting word from the Department of Health and Human Services on standards forelectronic attachments -- test results, x-rays, or anything else that could be sent electronically as part of a prior authorization request. The push to standardize handling of attachments began with the Health Insurance Portability and Accountability Act (HIPAA) back in 1996, according to Robert Tennant, director of health information technology policy at the Medical Group Management Association.
HIPAA included a directive for the federal government to develop standards for electronic attachments, but that provision didn't seem to be getting any results, so when the Affordable Care Act (ACA) was passed in 2010, it too included a provision requiring the federal government to issue a final rule on standardizing electronic attachments. The ACA provision, which was included in Section 1104 of the law, even had a deadline: Jan. 1, 2014. But that day has long since passed without any action.
"We have not heard anything yet; we anticipate that standard will be coming out soon," said Todd. "That's a key component of the prior authorization process as well. Until that attachment standard can come out and CORE can put operating rules around how to use that standard, it will be a component of prior authorization that will continue to be manual."
WASHINGTON — Medicare's new "Primary Care First" program for paying primary care doctors who see Medicare patients maintains a fee for office visits while also paying a monthly per-beneficiary amount for care coordination and other "behind the scenes" work that doctors do. So what's not to like?
Plenty, according to Harold Miller, president and CEO of the Center for Healthcare Quality and Payment Reform, in Pittsburgh. "Part of challenge with primary care is that the benefit is going to be in the longer run, not the shorter run. This model is very focused on trying to do something to save money in the short run; it's focused almost exclusively on reducing hospitalizations."
The Primary Care First program, which was announced April 22 by the Centers for Medicare & Medicaid Services (CMS), has two models, both of which would let primary care clinicians move away from fee-for-service and allow them to stop worrying about up-and-down Medicare revenue, according to the CMS. The agency would pay monthly population-based payments along with a simple flat fee for primary care visits. The program is slated to begin in January.
Two-Sided Risk
One of the models focuses on a more general population, while the second model is for advanced primary care practices that typically provide hospice or palliative care services and want to take responsibility for high-need, seriously ill beneficiaries who currently lack a primary care practitioner and/or effective care coordination, according to a CMS fact sheet on the models.
The model involves a potential downside risk of 10%, and an upside risk or bonus of 50%, depending on patients' outcomes, and performance would be measured on "risk-adjusted hospitalizations" or "the ability to keep patients healthy at home," Adam Boehler, director of the Center for Medicare & Medicaid Innovation (CMMI), which developed the models, said at a press briefing. "For example, doctors that earn $200,000 today could earn up to $300,000 if their patients stay healthy." For 2020, the CMS has identified 26 regions where practices can participate.
The CMS says that the model's monthly per-patient payments will help doctors stop worrying about their monthly revenue cycle. However, as Miller noted in an article, "at the same time that Primary Care First eliminates the current E/M [evaluation and management] payments for face-to-face office visits for attributed patients, it creates a brand-new $50 fee for each face-to-face office visit, which is about half as much as the average amount primary care physicians currently receive from Medicare for office visits."
"Based on the current average frequency with which Medicare beneficiaries make primary care office visits, this means that more than 40% of a typical practice's payments would still be tied to face-to-face visits. As a result, if the practice is able to care for patients effectively with fewer office visits, it will lose revenue and it could be unable to cover its operating costs," he wrote.
Lack of Risk Adjustment
Another problem with the program is that a primary care practice would receive the exact same monthly payment for a patient regardless of how sick or healthy they are, Miller said. "Since an individual patient who has higher needs will require more time and resources from the practice than other patients, a practice that is caring for that patient will have to reduce the time and resources it devotes to other patients if the payment is the same."
And in addition to those issues, since Medicare payment programs are expected to be revenue-neutral compared with the current budget, "the payment is intended to be the same as what the practice is currently getting," although the practice will be expected to provide more services than before, including 24/7 patient access and integrated behavioral healthcare, Miller said.
Miller is a member of the Physician-Focused Payment Model Technical Advisory Committee (PTAC), which advises the CMS on Medicare alternative payment models. "In general, I think there's been a lot of concern for a long time about [the] need to provide better support for primary care, and most payers in the country have been trying to do some kind of medical home programs for quite a while," he said. "Medicare has been fairly slow to the game on that."
In particular, Miller is disappointed that the CMS hasn't shown much interest in pilot-testing the payment models that PTAC has recommended. "With PTAC, two proposals [were submitted] for primary care, and we reviewed them and recommended they be tested and implemented ... It's been a long time since the recommendations were made, and the surprising thing to me was that the [Primary Care First] model that was announced by [the CMS] really didn't look at all like the models recommended by PTAC."
Room for Improvement
There are ways that Primary Care First can be improved, Miller said. For starters, "rather than creating a whole new set of office visit payments, what primary care practices have asked for is to get all or most of their payments as a flexible monthly payment so it's not tied to office visits."
In addition, the monthly payments should be higher for patients who require more care. "If you have more diseases and more care challenges, you're going to require more attention from your primary care physician," said Miller. "The way that happens today is more office visits ... but we don't want to pay more only if they come to the office."
When asked during a press briefing about the Primary Care First model, CMS administrator Seema Verma said the agency was trying to give physicians a variety of options. "What we tried to do is recognize that providers are in different places in terms of their ability to take on risk," she told MedPage Today. "What we've tried to do in this model is provide different options ... Some providers may say 'I want to take full risk on,' so we've allowed for that option."
"What we want to do in primary care is have them focus less on revenue cycle ... and actually be able to focus on patients," she continued. "The requirements around 24/7 [availability] — the idea there is that it's based on some work we've already done in primary care and some of [it is] 'lessons learned'; we're looking at what we know works."
Some providers differ with that assessment. "I know it was well intentioned, but [the] CMS seems not to understand the day-to-day mechanisms of [how] primary care practices work," Jean Antonucci, MD, a family physician in rural Maine and the author of one of the alternative payment model proposals that was recommended by PTAC, said in an email. "It is really virtually impossible to figure out how much revenue a practice will receive."
"Supposing that my patients are well taken care of so I am placed in the lowest [payment] category of $24 a month; it's very difficult to [keep patients] out of the hospital for $24 a month, but I might be put in that category because I did a good job. So no good deed will go unpunished," she said.
In her own proposal, she considers the cost of an hour's worth of phone calls — 15 minutes, four times a month — from a practice to a particular patient. "A [medical assistant] is $15/hr. easy, but often the doctor must be involved, or an RN, and that is $40-$150 per hour, plus they need the driver's license form or the forms for oxygen ... We end up with whining by doctors about not being paid, while payers and pundits complain we want to nickel-and-dime them to death."
Other Possible Approaches
Primary Care First's early reviews "reveal that longstanding conflicts remain between, on the other hand, budgetary savings and administrative feasibility goals and, on the other hand, more ambitious desires in parts of the medical community redesign care to elevate the role of effective primary care (regardless of the short-term costs)," Tom Miller, JD, resident fellow at the American Enterprise Institute, a right-leaning think tank, said in an email. "Perhaps more medical outcomes per se could be improved by simply paying primary care doctors more, but that assumes away the political food fight it would require to get there."
A more straightforward approach to "subsidize patients more directly to find and receive the care that they could choose to receive would upset providers either benefiting from the current system or imagining that they could be winners in the next round of political reimbursement roulette, labeled 'value-based,'" he added.
Gail Wilensky, PhD, senior fellow at Project HOPE in Bethesda, Maryland, and a former CMS administrator, said in an email that the difficulty with the model "seems to be the amount paid is too small and too unreliable ... That is certainly consistent with the ongoing CMS attempts. It is certainly reason to be skeptical although the results will only become clear after it is tried, assuming [the] CMS goes forward with it ... It has been discouraging how difficult it has proven to be to affect change in this area."
