Higher levels of the omega-3 fatty acid eicosapentaenoic acid (EPA) found in the blood appear to explain why icosapent ethyl drives down the risk of a cardiovascular (CV) event.

REDUCE-IT: Serum EPA Levels Key to Vascepa's CV Benefits

We interview experts on investigational treatments such as liso-cel, and ask how to bring them to community practice.

Spotlight on CAR T-Cell Therapy

The American Journal of Accountable Care® features research and commentary on new payment models.

New Members for AJAC Board

Vamshi Rao, MD, is an attending physician of Neurology at Ann and Robert H. Lurie Children’s Hospital of Chicago and assistant professor of Pediatrics (Neurology and Epilepsy) at Northwestern University Feinberg School of Medicine.

Now that there are 3 treatments options for patients with spinal muscular atrophy [SMA], do you foresee any clinical guidelines being developed and if so, what do you think would be their focus?

 I think we'd have been, over time, modifying our standard of care guidelines. The most recent modification was 2 to 3 years ago and that happened after a long time after the previous modification. This modification to the standard of care guidelines was pushed because nusinersen [Spinraza] was approved. Now, we have 2 drugs [approved] after that. So, I'm confident that we need more modification or change in our standard of care, especially because our natural history, in terms of what an individual with SMA looks like, is absolutely modified. It's different. And thank goodness, it's different. What do we do with these modified natural histories is going to be the subject of the new standard of care guidelines. The child that was not destined to sit up or walk is now sitting up and walking. What does that mean for bone health? What does that mean for their orthopedic manipulations in the future? How do we deal with scoliosis in children who were not supposed to get scoliosis? And vice versa? It's a very vast question and I don't think we'll be able to deal with every aspect of it today, but I think we will need to change and modify our standard of care guidelines. And those standard of care guidelines will also need to talk about or touch upon what we think about combination therapies.
My analogy to that I use comes from the world of oncology. When we started looking at cancers in children, we started using drugs and we found that those drugs were riddled with side effects, but they had some benefit of prolonging life. So, we kept using them. Then, we found out that we could make better drugs but we realized that we actually had to combine those drugs. Over time, we realized we not only had to combine them, but we also had to look at the genetics of the particular cancer to personalize those drugs. I think we're moving in that same direction with SMA. We started with a drug, and there were nowhere close to the side effects that we experienced with the cancer drugs, so that's definitely better. The cost of the drugs is sometimes limiting in terms of how the insurance companies allow us to combine drugs. We have to look at each child and say what stage they are, what developmental milestones they haven't hit. What is the gap that we still have in terms of these children attaining the next level? What standard of care guidelines should be put into place, as well as combination therapies and potentially new therapies in the future? So, it's a very it's a very hopeful world, but it's a world and a future filled with a ton of questions that we need to answer before we get there.

Videos

Vamshi Rao, MD, attending physician of Neurology at Ann and Robert H. Lurie Children’s Hospital of Chicago discusses how new treatments will influence future care guidelines for spinal muscular atrophy (SMA).

Dr Vamshi Rao Discusses Possible Future Guidelines for SMA Care

 (CLL) or CLL-like disease may accelerate the development of myeloid neoplasms, with the risk estimated to be 13 times higher in those with treatment than those without, according to a new study.

, may have implications for the treatment of CLL/CLL-like disease. CLL is the most common leukemia among adults in the Western world. Small lymphocytic lymphoma (SLL) is its nonleukemic variant, which can show up in the nodes, the spleen, or in tumors outside the bone marrow in the other tissues or organs. It usually has a slow course, with a median survival of more than 10 years. The introduction of more aggressive first-line drugs, including antimetabolites that mimic the structure of metabolic purines in combination with alkylating agents, has led to improved survival, particularly for myelodysplastic syndrome and acute myeloid leukemia.

The authors noted that it is well documented that the risk of secondary neoplasms in patients with other primary malignances is higher than in the general population. Some have theorized that the higher risk might be from the effects of chemotherapy or radiation, while those without prior treatment might simply be predisposed to developing the malignancies.

However, since myeloid neoplasms occur with some frequency in patients with CLL/CLL-like diseases who have not been treated, the authors said, that would have seemed to rule out the therapy causing the myeloid leukemia’s progression. The motivation for this study, therefore, was to better understand the development of myeloid neoplasms in this setting.

The authors compared the clinical and pathologic features of myeloid malignancies in 33 patients who had received treatment with 33 who had not. The cases with primary bone marrow involvement were selected from a 20-year period between 1999 and 2019. All patients with CLL/CLL-like disease diagnosed within 3 months preceding of identification of myeloid neoplasm were considered as cases “without treatment” regardless of whether treatment began in that timeframe or not.

The study showed that those who had been treated were younger (median age 65 vs 71); had a higher fraction of myelodysplastic syndrome (64% vs 36%; odds ratio [OR], 3.1; 

 <.05); a higher rate of adverse unbalanced changes to the structure and function of chromosomes, including complex changes,−5/5q- and/or −7/7q- (83% vs 28%; OR, 13.1; 

 <.001) and a shorter overall survival (median, 12 vs 44 months; 

The increase in risk may be based on the latency of myeloid progression of the leukemia and the cytogenetic profile, the authors said.

Twenty-three (70%) patients died of disease progression or complications among the 33 who were treated; 18 of 30 patients who had information available for analysis (60%) died in the group that was not treated (

The authors said they believe their study of myeloid malignancies in the setting of CLL/CLL-like disease is the first to compare patients with prior treatment for neoplasms to those without. The study shows that the 2 categories of patients with myeloid neoplasms have distinct features in clinical presentation, spectrum of myeloid neoplasm, morphology, cytogenetic profile, and clinical outcome.

More sophisticated epidemiological studies are needed to understand why these differences exist, the authors said. Previous work has suggested that the combination of several agents including fludarabine and other agents, including cyclophosphamide, rituximab and/or other therapeutic agents could have a synergistic effect. In the current study, 80% of the patients had been treated with fludarabine and alkylating agents.

They suggested that fludarabine may enhance chromosomal aberrations and mutational events by promoting the activity of the alkylating agents. Another explanation would be that it facilitates myeloid leukemogenesis by preferential selection of a myeloid clone with a mutator phenotype.

The introduction of new drugs, such as Bruton’s tyrosine kinase inhibitors, PI3 kinase inhibitors, BCL2 inhibitors (venetoclax), immunomodulators, and chimeric antigen receptor T-cell therapy may affect the epidemiology of myeloid malignancies, the authors said.

et al. Myeloid neoplasms in the setting of chronic lymphocytic leukaemia/chronic lymphocytic leukaemia-like disease: A clinicopathological study of 66 cases comparing cases with prior history of treatment to those without. 

 Published online: February 4, 2021. doi:10.1136/jclinpath-2020-207334

Articles

A recent study tries to discern if treatment for chronic lymphocytic leukemia (CLL) or CLL-like disease accelerates the risk of myeloid neoplasms.




Does Treatment for CLL Accelerate Myeloid Neoplasms? 

A recent report describes how researchers used a more precise bone marrow test in an effort to improve the outcome of a 72-year-old man with 

 (MM) by pinpointing the sensitivity of his myeloma cells to the most effective options. 

Such tests could help oncologists determine more precise therapies for older, frail patients.

The authors note that while advances in drug development have improved outcomes for younger patients, older, frail patients have not seen similar benefit. Clinical trials in hematology and oncology tend to focus on younger subjects, leaving the applicability to older patients somewhat unknown.

 researchers from the University of Colorado Anschutz Medical Campus described a test they developed called Myeloma Drug Sensitivity (My-DST) that correlates well with clinical outcomes. My-DST is a rapid drug sensitivity test of plasma cells that can deliver results within a week.

The authors surmised that frail patients have not benefited from MM advances because younger patients can tolerate 3-drug combinations, while frail patients can often tolerate only 2 at a time.

Thus, they said, it is critical to do more to ensure that the 2 selected drugs have the best chance of success. Using personalized treatment could help move the needle in treating frail patients by avoiding undertreatment, limiting attrition of subsequent lines of therapy, reducing exposure to ineffective drugs, and streamlining the management of relapses. Older patients on average attempt subsequent lines of therapy less frequently, contributing to worsened survival outcomes.

Other cancers have seen progress with personalized medicine, the authors said. For example, inhibitors of epidermal growth factor receptor mutations have been shown to be tolerated even in patients 80 or older with non

However, no precision instruments have been available for MM, which comprises 10% of all malignant cancers, with a median age of onset of 70 years. MM is a more difficult disease for which to provide a rational targeted therapy design due to the genetic heterogeneity of the disease, the study said, with multiple causes and a lack of targetable abnormal gene products.

My-DST is a phenotype-targeted approach profiling primary tumor samples. Unlike other published platforms, the functional assay avoids CD138+ cell selection of bone marrow, optimizing the viability of plasma cells and maintaining their microenvironment, the study said. As a result, indirect drug effects that occur via other immune cell populations can be measured, such as monoclonal antibody responses via antibody-dependent cellular cytotoxins.

My-DST involves bone marrow aspirants that undergo mononuclear cell selection, followed by incubation for 48 hours with a panel of antimyeloma drugs and untreated controls. Each treatment condition is then assayed for plasma cell survival after treatment using multiparameter flow cytometry.

The panel of therapies includes proteasome inhibitors, immunomodulatory drugs, steroids, alkylator chemotherapies, and monoclonal antibodies. The percentage of cell death is measured with high-throughput multiparameter flow cytometry. Drugs that kill more than 20% of cells are predicted to be active agents, the authors said.

The man in the case was diagnosed with IgA‐lambda multiple myeloma after presenting with pain in his sacrum and had a Karnofsky Performance Score (KPS) of 60; an MRI showed multilevel metastatic disease and a bone marrow biopsy showed 10%–15% monoclonal plasma cells. Cytogenetic abnormalities included an atypical IGH rearrangement, monosomy 13, and loss of 1copy of 14q32. He was staged as low-risk as per the Revised International Staging System criteria.

The My‐DST showed sensitivity to proteasome inhibitors and dexamethasone, but relative resistance to the immunomodulatory drugs.

However, the treating physician was unaware of the testing results, and the patient began induction treatment with immunomodulatory drug‐based therapy lenalidomide and dexamethasone weekly. After finishing 2 cycles of therapy, he achieved only a minor response (< 25%) in reduction in monoclonal protein.

He was then switched to bortezomib and dexamethasone as the next line of therapy. As predicted by his My‐DST result, he rapidly achieved a very good partial response as determined by an M‐spike detectable only by immunofixation and a significant decline in the lambda free light chains to normal levels and his KPS improved to 100. He did well for the next 2 years, and died a year later of natural causes, prompting the authors to call the treatment a success.

Hematologic malignancies are more promising targets for personalized medicine because patients’ bone marrow samples are readily available and are amenable to culture for measuring drug effects, the researchers said.

The authors said even though advancing age is the greatest risk factor of cancer, clinicians can’t rely on chronological age as a way to predict drug tolerance or treatment outcomes in older patients.

“Thus, going forward, it is of utmost importance to include a universally accepted frailty scoring system in cancer clinical trial enrollment to quantify the bias toward younger patients and allow better subanalyses of broader findings in frail persons,” the authors wrote.

Reiman, LT, Walker, ZJ, Babcock, LR, et al. A case for improving frail patient outcomes in multiple myeloma with phenotype‐driven personalized medicine. 

. Published online February 16, 2021. doi:10.1002/aac2.12022

Researchers describe the case of an older patient who underwent myeloma drug sensitivity testing as part of an effort to identify the therapies most likely to produce a response in this difficult-to-treat population.



Report Describes Case of Improved Outcome in MM With Personalized Medicine 

 to clinical trials based on their next-generation sequencing (NGS) testing results carries poor predictive value, claim researchers, who say efforts are needed to alleviate this burden put on the provider.

According to the researchers, 88% of trials initially matched to patients were eventually classified as false positives when manually screened by a provider 

Typically, when a patient gets their NGS report with clinical trial recommendations based on their diagnosis and identified biomarkers, physicians review the report to eliminate any false-positive trials to best determine appropriate trials for their patients. Data has indicated that research nurses can spend between 4 to 9 hours determining a patient’s eligibility for a clinical trial.

“As the cost of sequencing decreases and the clinical focus moves from limited gene-panel testing to whole-exon sequencing, RNA sequencing, and ultimately to whole-genome sequencing, the pool of potentially matching trials—that requires manual review—will expand,” reflected the researchers. “Informatics tools that assist in refining the trials that need to be manually reviewed or suggest potential matches based on the patient’s clinical and biomarker profile may reduce the manual burden of this process and reduce the barrier to trial enrollment.”

Across the 82 patients included in the study, the algorithms curated 808 trials, which were then filtered to 755. Of these, just 87 were considered matched trials following the manual prescreening.

The high rate of false positives identified by the researchers in the study stem from several factors, most often due to administrative details of the trials. For example, patients were often matched to a clinical trial that was either closed to enrollment, did not have openings, was never opened at the study site, or was halted while other arms of the trial continued.

On a global level, data is sometimes not readily be available to the local institution in real time, particularly for phase 1 trials.

“it is important to uncover the factors that result in a high rate of false positives while generating clinical trial recommendations,” explain the researchers. “Such studies can help to drive efficiency and improve the design for future trial matching efforts. Furthermore, such studies should be designed such that trial recommendations are sent to physicians in real time to maximize patient impact and generate enough learnings to inform design of a larger pragmatic study.”

Other factors influencing the false-positive rate included the presence of multiple malignancies.

Jain N, Culley A, Micheel C, Osterman T, Levy M. Learnings from precision clinical trial matching for oncology patients who received NGS testing. 

 Published online February 24, 2021. doi:10.1200/CCI.20.00142

According to new research, 88% of trials initially matched to patients were eventually classified as false positives when manually screened by a provider.



Automated Clinical Trial Matching Based on NGS Yields High Rates of False Positives

Patients with a lower socioeconomic status or more severe or treatment-refractory 

 were more likely to stop biologic use than other patients with severe asthma, according to a poster presented at the American Academy of Allergy, Asthma & Immunology 2021 Annual Meeting.

These patients were also more frequently living in urban areas and receiving care from pulmonologists instead of allergists or immunologists.

Severe asthma is estimated to impact between 5% and 10% of individuals with asthma. Patients with severe asthma often need care from a subspecialist and intensive therapy.

Although biologic therapies have been shown to reduce exacerbation risks associated with severe uncontrolled asthma and are increasingly being used, real-world data characterizing their use in subspecialist-treated patients with severe asthma is not well known.

The CHRONICLE clinical trial is an ongoing observational study incorporating real-world data on the patterns of patients aged 18 years or older stopping, switching, and continuing use of biologics in the severe asthma population. Patients had to be receiving a monoclonal antibody therapy, a systemic corticosteroid, or other systemic immunosuppressants for 50% or more during the previous year.

Investigators compared clinical characteristics and outcomes associated with asthma for patients enrolled from February 2018 through February 2020 who switched from 1 biologic to another, stopped biologic therapy, or continued biologic use. Data was collected at the time of study enrollment and was updated every 6 months.

Of the 1884 patients enrolled, 1294 (69%) used at least 1 biologic during the study period. In total, there were 1494 biologics uses recorded for 5 biologics:

There were 134 switches, 101 stops, and 1222 continuations, with several of the 1294 patients qualifying for more than 1 category of biologic use. More than 90% of patients with severe asthma taking a biologic continued taking a biologic through the last data collection compared to 10% of patients who switched biologics and 8% of patients who stopped.

Patients who stopped biologics were more often diagnosed with severe asthma at a younger age, less likely to have full-time employment, more likely to have Medicaid insurance, and more likely to be living in urban areas than patients who continued using a biologic or switched to another biologic.

These patients were also more often treated by a pulmonologist, more likely to have disability related to their asthma, had more maintenance systemic corticosteroid use, and had a lower quality of life as characterized by lower scores for the St. George Respiratory Questionnaire.

Patients who switched from 1 biologic to another were found to have a higher prevalence of nasal or sinus polyps and sensitivity to nonsteroid medications with anti-inflammatory effects.

Investigators noted that the most common reasons reported for switching from or stopping biologic therapy were worsening asthma, reduced medication effectiveness, and medication ineffectiveness.

The investigators noted that patients who continued biologic use likely had better disease control at study enrollment, suggesting that patients with less asthma control at baseline may not see a benefit with biologic therapy. For these patients, more therapeutic options might need to be explored in the future.

Soong W, Ambrose CS, Carstens D, Trudo F, Moore WC, Panettieri RA. Which severe asthma patietns are switching, stopping, or continuing biologic treatments? Presented at the American Academy of Allergy, Asthma & Immunology 2021 Annual Meeting, February 26-March 1, 2021; Poster 178.

Although 90% of patients with severe asthma choose to continue using a biologic, patients with worse disease control at baseline or with lower socioeconomic status (SES) may be more likely to cease biologic use, according to a poster presented at the American Academy of Allergy, Asthma & Immunology 2021 Annual Meeting.

Patients With Lower SES or Uncontrolled Disease May Be More Likely to Stop Biologic Therapy

 is well known, little information has been available about the renal effect on pediatric patients hospitalized with the virus and multisystem inflammatory syndrome in children (MIS-C).

But a retrospective study out this week examining the effects of COVID-19 and the associated inflammatory syndrome on 

 (AKI) in these young patients found that the complication was not uncommon.

, was carried out in the New York City area in 4 hospitals owned by Northwell Health, looking at hospitalizations from March 9, 2020, through August 13, 2020.

The researchers used the CDC definition for MIS-C, which includes children who presented with fevers, significant evidence of inflammation, and evidence of dysfunction in 2 or more organs, and tested positive for current or recent SARS-CoV-2 infection.

Of the 166 children admitted for acute COVID-19 or MIS-C, 152 patients were included in the study, with 97 patients (63%) admitted for acute COVID-19 and 55 patients (36.2%) diagnosed with MIS-C.

Overall, AKI developed in 18 (11.8%) of all patients.

Of children diagnosed with COVID-19 alone, the median age was 8.2 years and more than half were male. Eight patients (8.2%) developed AKI; 4 presented with AKI on admission; 6 had stage 1 AKI, and 2 had stage 3 AKI. There were no significant differences in age, sex, race, and body mass index (BMI) among children with and without AKI. Other findings showed that 50% of patients with AKI had gastrointestinal symptoms, and AKI was linked with significantly lower serum calcium and albumin and significantly higher baseline white blood cell count.

Children hospitalized with MIS-C were a little younger (median age, 7.5 years) and again largely male. AKI was higher in these patients (10, or 18.2%) than in those with COVID-19; 80% had AKI on admission. Those with AKI had greater BMI and all had gastrointestinal symptoms. In addition, patients with AKI had lower median left ventricular ejection fraction as well as systolic dysfunction.

In addition, children identified as Black were 2.86 times more likely to have AKI (95% CI, 1.04-7.93; 

Patients with AKI had higher rates of vasopressor treatment and ionotropic support. Continuous kidney replacement therapy was needed in 2 children with COVID-19; 2 others needed extracorporeal membrane oxygenation. Two patients in the COVID-19 group died; no patients died in the MIS-C cohort.

The cases of AKI resolved by the time of discharge, the authors said, although these children had longer hospital stays.

Previous estimates of AKI in children have varied from 1.4% to 44%, and the authors said that likely reflects the heterogeneity of study populations or definitions of AKI. 

"Further research in larger cohorts is needed to characterize AKI risk factors in children with acute-COVID-19 and MIS-C," the authors concluded.

Basalely A, Gurusinghe S, Schneider J, et al. Acute kidney injury in pediatric patients hospitalized with acute COVID-19 and Multisystem Inflammatory Syndrome in Children associated with COVID-19. 

Published online March 3, 2021. doi:10.1016/j.kint.2021.02.026

A retrospective study looking at pediatric patients hospitalized in 4 New York hospitals in 2020 with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) found that acute kidney injury (AKI) occurred in 11.8% of patients. 

Study Describes AKI Incidence in Children With COVID-19, MIS-C 

Although federal guidelines recommend patients with 

 have regular physical activity, actual exercise rates lag. Survey results presented recently at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2021 Annual Meeting found that most specialists were not aware of these physical recommendations, however, suggesting a possible role for them to play.

The researchers sent a 15-item survey to 979 randomly selected AAAAI members to ask about their self-reported awareness of physical activity recommendations and their current clinical practices. Respondents were asked to rate their knowledge about a variety of topics related to asthma and physical activity on a scale of 1 to 5 (1 = no knowledge, 5 = very knowledgeable).

The overall survey response rate was small (9.3%); of those who did answer, the majority were allergists or immunologists with an average of 18.1 years in independent practice.

Of those who responded, 80% of participants were not aware of specific physical activity guidelines for patients with asthma, while 66% said they were aware that moderate exercise has shown improved outcomes for these patients.

The survey also revealed the 3 main barriers to more direct involvement for providers to counsel their patients with asthma about exercise: limited time to discuss, lack of knowledge about how and when to refer patients, and the need to prioritize other health behaviors.

The survey asked about existing knowledge gaps that needed to be filled in order to provide assistance to their patients. Most were unsure about how much they knew about how to refer patients to a supervised exercise program, which patients to refer, or how to counsel patients. Some respondents reported having no knowledge about any of those considerations.

97% agreed that patients with asthma should exercise, while 84% agreed when asked if patients with severe asthma should exercise

90% support the idea of incorporating exercise counseling into practice, while only 69% actually did so

62% indicated they were knowledgeable about when to counsel patients on exercise

53% said they knew how to encourage patients to participate in exercise

Most agreed that there are 5 ways to facilitate this kind of knowledge to their patients, including patient handouts, posters in the waiting room, exercise referral forms, practitioner education, or emailed information to providers.

Nyenhuis SM, Gregory KL, Kahwash BM, Sharp LK. Asthma care provider perspectives on exercise promotion in people with asthma: An examination of knowledge, practices, barriers, and facilitators. Presented at the American Academy of Allergy, Asthma & Immunology 2021 Annual Meeting, February 26-March 1, 2021; Poster 127.

Asthma and immunology specialists responding to a survey about physical activity for patients with asthma were mostly unaware of any guidelines but seemed willing to learn more about how to incorporate them into practice.

Encouraging Patients With Asthma to Exercise Easier Said Than Done, Survey Finds 

Karen Kobelski is the Vice President and General Manager of Clinical Surveillance, Compliance & Data Solutions at Wolters Kluwer. She brings more than 25 years of experience to her position, which expands her previous leadership role over the Safety & Surveillance group to also include the Health Language portfolio of data normalization solutions.

CMS has made clear its intent to provide patients access to their health information in a user-friendly format, when and where they need it. The 

Interoperability and Patient Access final rule

 applies to CMS-regulated health plans, and the agency fully expects health plans to be ready for enforcement starting on July 1, 2021. That means there are just a few months left to prepare.

CMS further communicated their intent to advance the cause of interoperability when they released the 

Reducing Provider and Patient Burden Proposed Rule

 in December of last year. This rule would require automation of pre-certification activities using fast health care interoperability resources 

The federal push to liberate patient data requires a lot of work on the part of payers and their technology partners. In addition to modernizing legacy IT infrastructures, payers will need to be ready to shoulder the increasing burden of member transparency, and some payers are further along than others.

Plans should make no mistake that enforcement is coming and be prepared to do much more than check a box. Disparate and siloed data across health plan organizations will need to be completely transformed to achieve compliance but also to ensure sensitive patient information is protected and patients can understand the information being shared with them. Balancing compliance with patient comprehension and privacy is no small feat, but best practices are emerging.

CMS has identified FHIR as the key to unlocking valuable data for consumer and developer use and made clear its commitment to FHIR-based APIs in supporting the needs of patients and fueling innovation.

By July 1, payers must have in place a FHIR-based API that “allows patients to easily access their claims and encounter information, including cost, as well as a defined sub-set of their clinical information through third-party applications of their choice.” Further, as part of the 

, the ONC adopted the US Core Data for Interoperability standard for electronic health information to be accessed and shared using certified API technology. This standardized set comprises 16 data classes and 52 data elements.

Health plans will need to have robust data management and governance strategies in place. First, a single source of reverential data is required for the accurate exchange of information through FHIR APIs. Second, the ability to map non-standard data to the common health care terminologies that are identified in the FHIR implementation guides will become an essential component of their interoperability strategy. In short, a FHIR terminology service with advanced data mapping capabilities will prove to be a strategic advantage as health plans strive to capture maximum value from their data.

Certainly, the increased exchange of information will present new challenges to health data security and privacy. As health care organizations deploy the frameworks to support meaningful data sharing and greater care coordination across the continuum, one area that must not be overlooked is the compliant protection of sensitive health information. The mechanism for sharing data may be changing but the need to protect that data as it is exchanged remains the same.

Health plans may consider the use of sensitivity codes to help identify and filter sensitive diagnoses, procedures, labs and drugs across 6 key categories:

Sensitivity codes will require ongoing management and many payers are looking to experienced partners to fill that role.

Consumer-friendly descriptors for comprehension

Perhaps most important is acknowledging that for patients to act on their health data, they need to be able to understand it. The gap that exists between the language that clinicians and payers use and what patients understand is well known, but the Patient Access rule is forcing the issue to the fore.

The right strategy for effectively communicating with members and increasing transparency begins with terminology management that can generate consumer-friendly descriptions alongside industry codes within patient-facing documents. For instance, while a typical claim might designate a foodborne bacillus cereus intoxication, an accompanying consumer-friendly description would simply read food poisoning. These consumer-friendly descriptions may also be used in member portals, 

, and paper-based communications to truly engage patients.

By taking proactive steps to communicate with stakeholders—especially patients—payers can design and execute an implementation plan that not only satisfies the requirements of the Interoperability and Patient Access final rule but also moves the industry closer to the goal of putting patients truly at the center of health care.

In preparing for the upcoming implementation of the Interoperability and Patient Access final rule by CMS, best practices for health plans include prioritizing data mapping, sensitivity codes for privacy, and consumer-friendly language in accessible data for patients.

Contributor: How Balancing Compliance, Comprehension, and Privacy Can Optimize Access to Patient Data

The American system of insurance doesn’t work, because we give the best care at the lowest cost to the people who don't need it and the worst care at the highest cost to the people who do, noted Robert K. Massie, Jr, PhD, MA, of the Society for Progress. He was born with severe factor VIII hemophilia in August 1956 and contracted 

 in 1978, as well as hepatitis C, from contaminated blood products—and received care outside of the United States growing up, which he credits with saving his life.

Is insurance in the United States broken?

I mean, let me be really blunt about this. Most Americans do not realize how ridiculous we look to the rest of the world, which has solved the medical distribution problem going back to 1948.

I've traveled all over the world, and I just want to tell you: the absurdities, the bankruptcies, the failures, the poor medical outcomes that happen in the United States do not take place in most other countries. I've been treated in France, I've been treated in England, which people make fun of, and yet it's wonderful, wonderful care.

I, at one point in my career, toured and looked at the medical systems in Sweden and Denmark and Switzerland and Germany. Recently, I was in Italy. The Italian system is not perfect, but let me tell you something: no one in any of those countries ever, ever worries, are they going to get medical care. Just think about that. Whereas in the United States, medical costs are among the highest—in some cases, the highest—cause of medical bankruptcy and an untold number of horrible medical outcomes, and a huge amount of completely unnecessary stress in people's lives, as parents worry about their children or they’re seniors.

And the truth is, we've have more or less solved this if you happen to be 65. We have Medicare. I'm about to turn 65. But because of a really broken and perverse ideology in the United States, we are denying ourselves a system and a right that pretty much everybody else in the developed world has. And it's absolutely shocking.

I started working on this in the 70s. So here I am, I'm going on 45 years of looking at the question of national health insurance. And yet, as you might imagine, the system we have now, if you really think about it, the concept of insurance doesn't work here. Because insurance is based on the idea that we all get paid a little money but none of us knows who's gonna get their house burned down, for example. So we all pay a little fire insurance.

Modern medicine is about predicting accurately who's going to get which diseases. And as we become more and more genetically adept at figuring out who has a predisposition for a disease, then we can identify preexisting conditions before they exist. I mean, really preexisting, long before we actually even experienced them.

And so what do insurance companies do? They try and get rid of the people who need medical care, except for the fact that we now have Obamacare, which is still there, that prevents people from being kicked off.

To put as simply as possible: we give the best care at the lowest cost to the people who don't need it. And we give the worst care at the highest cost to the people who actually need medical care. And that's about as dumb as you can get, and yet that is an accurate description of the American system.

So yes, the outcomes would be dramatically better. We would be using preventive care rather than acute care, we would dramatically lower costs, and we would have much healthier people. But unfortunately, the American people do not realize what's happening in the rest of the country or have lost enough of their own sense of self-worth that they aren't willing to demand what virtually everybody else says because somehow we think it's impossible. That's sad. It's long overdue and needs to be changed.

The American system of insurance doesn’t work, noted Robert K. Massie, Jr, PhD, MA, of the Society for Progress.

Dr Robert Massie: The Insurance System Needs Fixing in the United States

The FDA Friday approved axicabtagene ciloleucel (Yescarta) for the treatment of adult patients with relapsed or refractory follicular 

 following 2 or more lines of systemic therapy.

The decision was based on data from the phase 2 ZUMA-5 trial (NCT03105336), in which the chimeric antigen receptor (CAR) T-cell treatment elicited a response in 91% of patients with relapsed or refractory follicular lymphoma (n = 81); 74% of patients had a continued remission at 18 months.

Among all patients with follicular lymphoma, the median duration of response was not reached at a median follow-up of 14.5 months.

In the safety analysis conducted in 146 patients, grade 3 or higher cytokine release syndrome and neurologic adverse effects were reported in 8% and 21% of patients, respectively.

, Kite, a Gilead company, said the approval marks the first CAR T-cell therapy approved for patients with indolent follicular lymphoma, follows FDA Breakthrough Therapy Designation and a priority review, as well as the third approved indication for a Kite cell therapy.

For these patients in the third line of therapy, the 5-year survival rate is only 20%, said Caron A. Jacobson, MD, MMSc, Medical Director, Immune Effector Cell Therapy Program, Dana-Farber Cancer Institute and Assistant Professor of Medicine, Harvard Medical School.

The FDA approved axicabtagene ciloleucel (Yescarta) for the treatment of adult patients with relapsed or refractory follicular lymphoma following 2 or more lines of systemic therapy.

FDA Clears Axi-Cel for Relapsed/Refractory Indolent Follicular Lymphoma

Despite many patients receiving medical evaluations, specialty referrals, and prescription therapeutics, almost 40% of 

 cases remained unexplained, according to a poster presented at the 

American Academy of Allergy, Asthma & Immunology 2021 Annual Meeting

Chronic cough is defined as a cough lasting more than 8 weeks. Unexplained chronic cough (UCC) is a chronic cough subset where an apparent cause for symptoms cannot be found after thorough analysis. It is estimated that UCC affects between 5% and 10% of American adults.

Despite an identified etiology, health care professionals pursue medication trials and imaging tests until a diagnosis is determined, which can put a large burden on the health care system and patients.

Primary care providers are usually the first health care specialists to evaluate UCC. However, it’s not clear how common UCC occurs in the primary care population.

Investigators set out to characterize the prevalence of new onset chronic cough presented to primary care clinics and identify those patients who were classified as having UCC.

The observational, retrospective study incorporated real-world data from the Northwestern Medicine Enterprise Data Warehouse electronic health record repository on adult patients visiting an outpatient primary care clinic within a tertiary center between 2015 and 2018. Patient charts were examined for 3.5 years from initial primary care physician visit.

During the study period, 122 patients visited a primary care physician. Of those patients, 98 were identified to be the final chronic cough cohort. Patients in this cohort had a mean age of 61.1 (15.3) years, were mostly White (74.5%), and were mostly comprised of women (67%).

Sixty-four patients received a referral to a specialist, 28.1% (n= 18) of which were for patients with UCC. Forty-five (45.9%) patients within the chronic cough cohort were referred to 1 or more specialists. The most common specialties referred to were pulmonology (31.6%), allergy and immunology (13.2%), otolaryngology (12.2%), and gastroenterology (8.2%).

The most common medications prescribed to patients with UCC were intranasal steroid or azelastine nasal spray (89.2%), antibiotics (70.3%), oral steroid (62.2%), acid reflux medication (59.5%), and inhaled corticosteroid either alone or in combination with a long-acting beta agonist (59.5%).

After 3.5 years after the first primary care visit, 61 (62.2%) patients were determined to have a chronic cough and 37 (37.8%) had UCC with no clear etiology.

Twenty-seven percent (n = 10) of patients with UCC who saw a specialist still did not have an apparent reason for their cough, whereas 62.2% (n = 61) eventually received a diagnosis. Of the patients who received an official diagnosis, 39.3% (n = 24) had a multifactorial cough that had more than 1 etiology.

The most common diagnoses found were gastroesophageal reflux disease (41.0%), rhinitis (39.3%), asthma (23.0%), and 

“Further clinical characterization will inform future research and treatment directions for chronic cough,” wrote the investigators.

Patel AK, Vu T-HT, Guo A, Sinard RN, Peters AT. Characterizing new onset chronic cough in primary care clinics. Presented at the American Academy of Allergy, Asthma & Immunology 2021 Annual Meeting, February 26-March 1, 2021; Poster 190.

Despite receiving specialty referrals and multiple prescriptions medications, nearly 40% of patients with an unexplained chronic cough are not given a proper diagnosis.

Nearly 40% of Chronic Cough Cases Remain Unexplained After Extensive Testing, Therapy

examines the current state of the tools used to evaluate health-related quality of life (HRQOL) in oncological trials, highlighting the efficacy and drawbacks of those tools when applied to patients with solid-tumor cancers undergoing immunotherapy. Given the high cost and potential toxicities of immunotherapy in these patients, developing and validating targeted and effective tools to evaluate HRQOL over the course of therapy in those patients should remain a priority, the authors wrote.

While immuno-oncology (IO) therapies have become a cornerstone in some cancer types and have undoubtedly improved traditional study end points in terms of survival, immune-related adverse events (irAEs) are a common effect of IO agents that can significantly affect HRQOL during and after therapy. Therefore, the authors stress the importance of adequate risk-benefit assessments to ensure that “meaningful and valuable” IO therapies are approved for the treatment of cancer and noted that unlike AEs that typically occur during treatment with other agents like chemotherapy, irAEs do not necessarily have a dose-response or dose-toxicity relationship.

“An evaluation of the benefit of these IO agents must include a determination of their effects on HRQOL to ascertain the real value of the treatments beyond traditional statistically significant efficacy,” they wrote. “HRQOL is a complex, abstract, and multidimensional idea that describes an individual’s satisfaction with life in the domains considered most vital.” This encompasses measures like general health (defined in the review as physical, social, and psychosocial health), as well as cancer- and therapy-related effects like symptoms and side effects.

 (PROs), which have become increasingly common in cancer clinical trials, as a key element of successful HRQOL assessment in patients on IO with solid tumors. Examples of oncology-specific PRO tools are the Functional Assessment of Cancer Therapy-General (FACT-G) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Both have been extensively validated, are familiar to most researchers, and are available in multiple languages.

The PRO adaptation of the National Cancer Institute’s Common Terminology Criteria for Adverse Events (PRO-CTCAE) has helped with collecting data on symptomatic AEs, although it was initially developed for either surgery, radiation, and/or chemotherapy—not IO therapy, which has additional relevant AEs— according to the study authors.

Despite the existence of these tools for cancer in general, authors raise the question of whether they are sufficiently sensitive to effectively monitor the HRQOL of patients undergoing IO treatment for cancer. The inclusion of symptomatic irAEs in such tools is paramount if they are used to monitor this patient population. And despite the differences between IO therapy and more traditional treatments, many trials utilize conventional HRQOL tools and consider HRQOL a secondary or exploratory end point, according to the review. Those are both limitations in gauging quality of life over the course of treatment and for risk-benefit assessment of IO therapies.

“Currently, there is no widely adopted, validated instrument that has been tailored for this patient population, although a tool to measure HRQOL has been developed in patients receiving immune checkpoint modulators,” the authors wrote. There are 2 major issues in PROs for IO therapy clinical trials, they said:

All the possible symptomatic irAEs from IO therapy need to be identified and translated into PRO items

Patient input is required to confirm that specific symptomatic irAEs impact HRQOL and then develop and validate tools or modules specific to the various classes of immunotherapies

The PRO-CTCAE, for example, does include items that that cover some of the more common irAEs—fatigue, rash, and pruritus. But some other common irAE symptoms—like tremors, neck swelling, muscle weakness, weight gain, shivering, or bleeding in stool—are not in the PRO-CTCAE item library. Although some efforts are underway to mitigate this knowledge gap, there is more work to be done, the authors concluded. That includes developing PRO tools for the new

 that are now being studied and added to the treatment armamentarium. Integrating PRO tools into early-phase trials to inform the development of tools for later studies will be key, they said.

“With the rising number of IO agents available, it has become clear that a more thorough understanding of irAEs is needed to generate a more complete picture of the risks and benefits associated with these treatments,” they wrote. “For this to occur, more comprehensive capturing of irAEs is required, and the effects of irAEs have on HRQOL must be evaluated. Efforts to develop these tools are underway and will be an important step forward in the understanding and accurate reporting of irAEs.”

Importantly, the HRQOL data collected from these trails will inform regulatory applications and ensure that new IO therapy approvals have undergone thorough risk-benefit and value analyses, ultimately affecting health care policy overall.

Voon PJ, Cella D, Hansen AR. Health-related quality-of- life assessment of patients with solid tumors on immuno-oncology therapies. 

Published online March 4, 2021. doi:10.1002/cncr.33457

A review published in Cancer examines the efficacy and drawbacks of tools used to evaluate health-related quality of life in immuno-oncology clinical trials.

Targeted PRO Tools Needed to Evaluate QOL in Immuno-Oncology Trials

Preliminary study results point to a possible connection between increasing global temperatures and an increased risk of hospitalization during the course of 

 that will be presented at this year’s American Academy of Neurology (AAN) 73rd Annual Meeting in April.

This greater risk stems from possible worsening symptoms, the authors noted. They compared visits for each patient during anomalously warm and normal weather periods. Their primary outcome of this retrospective cohort study was annualized warm weather–related risk of out/inpatient and emergency department visits in the United States, and they defined anomalously warm weather as “any month in which local average temperatures were higher than the long-term average temperature for that month by at least 1.5°C, or almost 2°F.”

Preliminary study results point to a possible connection between increasing global temperatures and an increased risk of hospitalization during the course of multiple sclerosis (MS).