Development and Use of a Pathway for Chronic Lymphocytic Leukemia: The US Oncology Experience

In this journal section, we speak with cancer care practitioners about their clinical pathways and the pathways programs being used in their practice, how they are being applied in a particular disease state, and what challenges persist regarding
treatment decision-making and personalized medicine integration.

In this “Pathways in Practice” installment, we speak with John Burke, MD, medical hematologist and oncologist at Rocky Mountain Cancer Centers (CO), and Aimee Ginsburg, PharmD, BCPS, director, Pathways and Clinical Content, McKesson, about the specific challenges and considerations for the creation of a clinical pathways in chronic lymphocytic leukemia (CLL) that is utilized throughout The US Oncology Network.

Could you give us a general overview of how clinical pathways are defined, developed, and implemented at US Oncology Network?

Dr Ginsburg: Over the course of the last 15 years, we have developed pathways for the most common cancers seen in community practice where providers would benefit from pathways guidance and clinical decision support. We have also determined which diseases do not need a pathway based on incidence, the treatment setting, or a small number of available treatment options. For example, if the disease is primarily treated inpatient, we often choose not to design a pathway.

After we determine the disease, we review the National Comprehensive Cancer Network (NCCN) guidelines for concordance then review data with the Pathways Task Force, a committee composed of expert providers in The Network. This review includes oncology-trained clinical pharmacists who outline a proposed pathway structure with details about how a physician approaches treatment decisions for a patient, including both diagnosis and treatment determination. We also consider any biomarkers that should be collected as well as disease characteristics that could help streamline the pathway.

We then gather literature and evaluate it in a similar fashion. Are there agreed upon best practices everybody should be using or is there a dichotomy? We look at published trials, breaking them down into their endpoints and assess the data through our three pillars: efficacy, toxicity, and cost.

From here, we create a preliminary outline of the pathway. We circulate it through the Pathways Task Force. We also look at current treatment patterns in our network to see if the pathway is in line with the way our providers are treating patients. We ask this larger group if they agree with the preliminary outline.

Our Pathways Task Force is made up of generalist and specialist physicians—either by interest or by actual patient population treated—who help determine if this pathway is logical and if the options apply to 80% of the patient population.

Once we get approval of a preliminary pathway via that process, it is sent to a disease research committee of physicians heavily involved in research or extremely interested in this specific disease for vetting. From here, the pathway is circulated more broadly to our 2000 physicians and providers in The Network for further review and approval, as “Here is what we put together. It’s gone through two layers of approval. Please provide feedback before it is added into the clinical decision support in the electronic health record.”

Can you elaborate on the role that your relationship with NCCN plays in the pathways development/maintenance?

Dr Ginsburg: The collaboration we have with NCCN is one in which our pathways are 100% concordant to the NCCN Guidelines—not 100% identical. That is, our pathways deliver a more narrow subset of treatment options that focus on efficacy, toxicity, and then layer in cost. We are in constant communication with NCCN about pending changes to the guidelines, and their panel members have the opportunity to participate on the Pathways Task Force and weigh in on potential updates to the pathways.

Could you provide more detail about US Oncology’s pathway for CLL? What is the approach to stratifying patients for this treatment pathway?

Dr Burke: In the CLL pathway, like all of our pathways, the stratification approach is what is used by the NCCN Guidelines. It has the same tenants of age, frailty, comorbidities, and genetic mutations that might drive treatment decisions.

We have a first line of options for initial therapy and then options for relapsed disease that physicians might choose from. That is kind of the general design of the pathway.

Are there arms or different paths within the treatment pathway for specific treatment related adverse events or end-of-life care? How specific is the pathway regarding patient reaction to treatment?

Dr Burke: Our pathways do not address those issues. The pathways are generally drug choices that might be chosen in the first line and then second line and beyond. If somebody had side effect number one, then you switch to a different drug. We don’t get that specific on the pathway. That is really left up to the treating physician. In a scenario like, If the patient has atrial fibrillation on ibrutinib, what would you do next? We leave it up to the physician what they choose for a specific side effect. End-of-life care is also not addressed by our pathways. Pathways are used for treatment decisions.

Can you speak about some of the benefits of a few of the current therapy options you use for CLL that your pathway support? Also, how are you ensuring that new therapy options are rapidly incorporated into practice or incorporated into the pathways?

Dr Burke: Our pathway includes all of the available therapies for CLL–from chemoimmunotherapy regimens to BTK inhibitors and PIK3 inhibitors to BCL2 inhibitors. It is really just a matter of trying to help physicians pick the right treatment at the right time.

There are several ways that we keep up with new data coming out. One is that we have specialists who really focus on that field represented on our Pathways Task Force committee. This is what I do, for example: I see and treat a lot of CLL and go to all the meetings and hear about the latest data as soon as they come out. That is one way.

Our pharmacists, likewise, are really attuned to what is coming out in all these areas. As soon as an announcement about a new drug approval is made, then we are on that. We go to the big meetings like the American Society of Hematology (ASH) annual meeting and American Society of Clinical Oncology meetings or international meetings, and as soon as a major presentation occurs, we are tracking the data and our groups are assessing it. For instance, if I hear something at ASH, then I will let my colleagues on the committee know about that information and we will then bring it up at the next meeting to discuss.

Last but not least, there is communication between our committee and NCCN, so that if NCCN is making changes to their pathways we immediately hear about that. Even in draft form, before such changes are finalized, we are privy to that information.

Those are all the ways we stay up-to-date. Sometimes we will put drugs on pathways before the Food and Drug Administration (FDA) has approved those drugs if we think that that is the right thing to do for patients and we think FDA approval is imminent. We are ahead of the FDA often, in terms of our approvals for pathways yet still contained within the NCCN framework.

Are there any specific CLL trials that you know of, or that you may even be involved with, that you think may be potentially practice changing or have implications for your pathway in the coming years?

Dr Burke: Yes, there are potentially practice changing studies within US Oncology. The pathways do not identify specific trials. We encourage clinical trials as a first-choice pathways-appropriate options, but the pathways are really more for providers to choose standard of care available agents.

Yes, there are potentially practice changing studies within our Network, but those are run independently of the pathways committee and do not impact the pathways directly at the moment.

What are some of the challenges to optimizing therapeutic decision making that you continue to see in your practice? How do you anticipate challenges like these might be overcome?

Dr Burke: One challenge that we are having right now is when there are multiple treatments available with different levels of evidence to support their use—how do we choose those? There are various levels of disagreement about how broad and inclusive the pathways should be.

For example, if three drugs are reasonable but one of them should be preferred, does the committee choose the one preferred drug or let all three reasonable drugs be on the pathway? A lot of that is opinion and not black-and-white science. We debate how narrow and focused our pathways should be—it certainly is a challenge that we face frequently on our calls.

That generates some disagreement in that the pathways might choose one thing, but other providers in The Network might not be happy with how narrow or broad we have chosen to be. Those are some of the challenges our committee faces on a regular basis.

Dr Ginsburg: I completely agree with that. I think the biggest challenge is the art of creating the pathway. Do we have to list all options because the data is somewhat equivalent? Do we pick one agent and try and steer The Network, our group of providers, to use one option? That is a constant struggle that varies by disease, and as Dr Burke was saying, by the makeup of our committee.

Dr Burke: Take the example of bladder cancer, where there are five checkpoint inhibitors approved for metastatic bladder cancer. How do you choose between those? We want our pathways to be as narrow as possible, focusing on effectiveness of the treatment, toxicities, and cost. Sometimes it is difficult to really distinguish between those, and you have multiple drugs available with equivalent efficacy, toxicity, and cost. That is another example of a challenging situation.

Are the providers in The Network generally receptive to the pathways that they have been asked to use, or does it vary on a case to case or disease to disease basis?

Dr Ginsburg: The quick answers to these questions are yes and yes. I mentioned that part of the process is the downstream approvals. Before the pathway is finalized and loaded into our electronic health record and the decision support, there is the opportunity for comment. There is always an opportunity to comment throughout the process.

There is also the convention that the pathways are supposed to be applicable to 80% of what is seen in community practice. Meaning, for 20% of the patients that walk through the door, there is a completely logical, realistic, and acceptable reason to not follow pathways. Was it an outside treatment recommendation? Is it patient preference? Is it patient comorbidities? There is always a way for providers to use clinical judgement to select an off-pathway regimen.  Our pathways are not restrictive where you have to choose one of the options or you may not proceed.

Is there a review process for off-pathway choices?

Dr Ginsburg: These reviews happen at the local practice level. Each practice gets to determine if the off-pathway treatment is acceptable.

Dr Burke: Each practice is a little different in this. For example, in my practice, if I order something that is off pathway, it will be reviewed by a small review committee, and they will have a vote about whether it is reasonable.

If it is thought to be reasonable, then we just move forward. If it is not thought to be reasonable, I can still do that but it puts me at financial risk if that treatment is not covered by the insurance. That is the implication; I can still treat off pathway as much as I want. There is no requirement that I adhere to pathways.

Is there any incentive program or anything similar across The Network for providers to be on pathways?

Dr Burke: There are two incentives. The first is that if I choose to treat off pathways, then I might be financially at risk for failure of the insurance to pay for that off-pathways treatment. That is only an exceptional circumstance, because 99% of off-pathway treatments are reasonable, and they are approved by this committee.

There is more of a disincentive to stay off the pathway. Some practices have financial incentive built in for physicians to adhere to pathways, so that if somebody’s pathway adherence is very low and they are often treating off pathway, there might be a financial disincentive. That really depends on the practice.