ASH Clinical News ACN_4.10_FULL ISSUE web | Page 10

Editor ’ s Corner

Caring About Standards of Care

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The content of the Editor ’ s Corner is the opinion of the author and does not represent the official position of the American Society of Hematology unless so stated .
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’ VE BEEN THINKING a lot about standards of care recently .
A “ medical standard of care ” is actually a legal term , typically defined as the level and type of care that a reasonably competent and skilled health-care professional , with a similar background and in the same medical community , would have provided under the circumstances that led to the alleged malpractice . Caught your attention with that last word , didn ’ t I ? In my world , discussions of standards of care arise outside of malpractice considerations ( fortunately , and I am knocking wood as I write this ), and with some regularity , in two specific instances : defining standard therapies for patients with hematologic conditions or cancer , as opposed to what should be considered research ; and identifying standard testing , office visits , and therapies for patients on clinical trials , distinguished from those that are considered “ research specific .”
The first instance comes up frequently when we discuss drugs that comprise our formulary at Cleveland Clinic . I chair the Medical Staff Pharmacy and Therapeutics Committee for the entire enterprise , which is the group that decides what makes it onto our formulary and thus what is stocked in our pharmacy . Our purpose is to promote the rational and appropriate use of drugs within our health system , with the goal of improving safety and patient care .
By implication , the drugs that we approve also are getting the nod from our staff physicians as standards for the medical care of our patients . That imprimatur has substantial consequences for pharmaceutical companies : Our organization is large , and we may be the top prescriber of a medication in the world .
Nine separate pharmacy and therapeutic subcommittees ( such as Hematology / Oncology , Neurosciences , Cardiovascular , etc .) report to our parent committee with recommendations for drugs to be added to the formulary within their specialties . Our discussions may be more far-ranging than those that the U . S . Food and Drug Administration ( FDA ) or its Oncologic Drugs Advisory Committee have when recommending regulatory approval of a drug . In contrast to the limitations placed on their considerations , we can discuss issues such as drug cost and we aren ’ t under the same pressures of political expediency . Thus , we may vote against a drug being added to formulary if we feel its relative balance of safety and efficacy is not favorable , despite its regulatory approval .
We also may place restrictions on drug use to encourage appropriate use , and limit overuse ( particularly with expensive drugs ) – even if these guidelines don ’ t align with the FDA label . This gets into standards of care .
What happens when someone at our institution uses a drug off-label ? Most of the therapeutic approaches we recommend in hematology and oncology are actually off-label , so restricting use only to populations included in registration studies would cripple our practice of medicine . So , we allow it in our guidelines . But how do we know if drug use is a bit too far off-label ? For example , the FDA approved enasidenib for the treatment of patients with relapsed or refractory acute myeloid leukemia who harbor an IDH2 molecular abnormality . Is it acceptable to use the drug in patients with myelodysplastic syndromes ( MDS ) who harbor the same mutation , as one clinical trial did include 17 patients with MDS ? This is where we borrow a bit from the lawyers .
Our policy is to allow off-label use if a physician can identify at least one well-designed phase I or phase II study with an acceptable balance of safety and efficacy in a similar patient population , and two colleagues from comparable institutions can confirm that this approach is considered a standard ( what we call our “ 1 + 2 ” policy ). For molecular-driven therapy , we also have an off valve for recommendations coming from one of our genomics tumor boards .
Thus , for the patient with MDS and an IDH2 mutation , we could consider enasidenib a standard based on the clinical-trial data , and if two colleagues at comparable institutions agreed it was a standard . If a physician can ’ t meet that bar , we consider use of the drug for the proposed indication to be research and recommend a single-patient investigational new drug application , or an alternative approach .
Mikkael A . Sekeres , MD , MS , is director of the Leukemia Program at the Cleveland Clinic in Cleveland , OH .
We also identify standards of care every time we conduct a clinical trial . In clinical research , it is our responsibility to go meticulously through a trial to determine which tests , visits , or treatments are considered a standard part of medical care , and which are not .
Why do we go through this onerous process ? Well , to be honest , to avoid Medicare fraud .
The law requires health insurance companies to pay for the “ usual care ” of medical conditions in those covered by the insurance . That makes sense , as it doesn ’ t seem fair that a patient with acute leukemia who sees her hematologist every two weeks would have those visits denied by insurance just because the biweekly visit occurs as part of a clinical trial . On the flipside , it wouldn ’ t be fair to force insurance to pay for EKGs that must be obtained within 10 minutes of each other in triplicate in an asymptomatic patient . We would identify the latter as being 1 ) purely for research purposes , and 2 ) a really dumb requirement . But I digress . Based on our determination , we bill insurance for some aspects of a patient ’ s care through a clinical trial and bill a study sponsor for the research aspects of that care .
The tricky part is how to decide what is “ standard .” It ’ s easy enough to say that a patient with higher-risk MDS would be treated initially with the drug azacitidine , whether she has enrolled in a clinical trial or is being treated off-study . It ’ s much harder to say that we would usually perform bone-marrow biopsies in that patient every … three months ? Six months ? Two months ?
If that patient were younger , we might agree that it should be de rigueur to perform a pregnancy test prior to her initiating chemotherapy . But is it standard to perform a pregnancy test prior to every cycle of therapy ? Many clinical trials require it .
To answer questions about treatment standards , we often rely on treatment guidelines , acknowledging that not all of those adhere to rigorous guideline-development guidelines . And no , it is not considered a syntactic standard to use the word “ guideline ” three times in one sentence .
But where do we turn for guidelines on testing frequency or standard tests ? I propose that guideline panels take this on – in addition to making recommendations about therapies – or that members of disease communities establish those standards . Otherwise , we may be leaving that decision to someone working at an insurance company who is having a particularly bad day .
And when we wrongly consider an aspect of a trial as a standard when it may not be , our patients may suffer the consequences by having to pay out of pocket at a time when they can least afford it .
Mikkael Sekeres , MD , MS Editor-in-Chief
8 ASH Clinical News August 2018