Suzanne Shelley, Pharmaceutical Commerce contributing editor

What makes specialty pharmaceuticals ‘special’? Other than cost (the primary criterion), it is often the tangled combination of patients’ health and personal situations, comorbidities, and complex forms of drug delivery (often, infusion). This, in turn, calls for a greater number of pharmacy services; thus, the specialty pharmacy.

But what makes a specialty pharmacy ‘special’? Besides the reality of being able to deliver the personalized follow-on services, the acknowledged way of signifying those capabilities is for the pharmacy to obtain accreditation from one or more accrediting bodies. These organizations define both baseline expectations and aspirational goals, by establishing standards, processes and protocols, based on updated clinical evidence and industry best practices. Such third-party accreditation has become more important than ever, as both the number of specialty medications and the number of players in the specialty pharmacy channel continues to grow.

Today, the primary players in specialty pharmacy accreditation are:

* The Center for Pharmacy Practice Accreditation (CPPA; https://www.pharmacypracticeaccredit.org ); CPPA is a nonprofit organization established through partnership of the American Pharmacists Association (APhA), the National Association of Boards of Pharmacy (NABP) and the American Society of Health-System Pharmacists (ASHP)

* Accreditation Commission for Health Care (ACHC; www.achc.org)

* The Joint Commission (TJC; https://www.jointcommission.org)

“Manufacturers of these high-cost therapies have a vested interest in making sure their specialty drug is working for patients, and manufacturers know that the drug has a better chance of success if they can be assured their specialty pharmacy partner is providing the highest level and greatest consistency of care, including the many patient-support programs that are needed,” says Heather Bonome, PharmD, Director of Pharmacy for URAC.

Today’s accreditation standards are written “to provide a baseline of quality of performance and to challenge an organization to stretch to perform to the highest level of industry best practices,” says Karen Saunders, Director of Quality Management & Accreditations for Express Scripts.

Drug Channels Institute’s 2018 update on the accreditation of specialty pharmacies

, [1] the number of specialty pharmacies with accreditation expanded again from 2017 values. “We identified 729 unique pharmacy locations that by the end of 2017 had achieved accreditation from the three major independent accreditation organizations, ACHC, CPPA and URAC,” says Adam Fein, Ph.D., president of Pembroke Consulting, which also operates the Drug Channels Institute. “The 2017 figure is almost double what it was in 2015.” He adds that pharmacy locations owned by healthcare providers—hospitals, health systems, physician practices, and providers’ group purchasing organizations—were the fastest-growing category.

“The accreditation process involves a comprehensive review of all the many processes that support quality patient care and promote patient safety, with an emphasis on ongoing performance measurement and validation,” says Rob Osborne, Vice President, Pharma Trade Relations, for Express Scripts. “Achieving one or more accreditation awards is a key benchmark that reflects not only the specialty pharmacy’s capabilities, but its commitment to ongoing improvement of services, as well.”

For instance, because specialty medications are often biologics that require complex dosing regimens and self-injection, specialty pharmacies often provide a full slate of educational programs to help patients understand their disease and their medication, understand and avoid potential drug-drug interactions, manage the complex drug-administration requirements prior to initiation of therapy and more. By providing continuous monitoring and periodic outreach to patients (using pharmacists or nurses), and reporting agreed-upon metrics back to the drug maker, specialty pharmacists provide the critical connective tissue needed to ensure optimal drug utilization over time for each patient.

The program-specific data and analysis the specialty pharmacy can provide helps drug makers track drug utilization and patient outcomes over time, and use the detailed insight to make ongoing program enhancements over time.

Meanwhile, many of today’s specialty medications have potential toxicity issues that trigger complex handling and reporting requirements under the drug’s FDA-mandated Risk Evaluation and Mitigation Strategies (REMS) program. Specialty pharmacies are in a good position to institutionalize the type of rigorous operational framework to manage REMS and comparable regulatory requirements.

“When we perform an onsite visit, we’ll look at individual patient records and profiles to see if the specialty pharmacy is meeting its requirements with regard to REMS,” says Lynnae Mahaney, B.S., Pharm., M.B.A., FASHP, ASHP Director of Pharmacy Accreditation, providing comment on behalf of CPPA, a joint initiative with APhA (American Pharmacists Association) and NABP (National Association of Boards of Pharmacy) and ASHP (American Society of Health-Systems Pharmacists). CPPA accreditation programs are administered by ASHP and NABP.

Oral oncology medications fall under the purview of specialty pharmacy because they often have a unique set of dosing and administration requirements to encourage optimal clinical outcomes, and a toxicity profile that must be closely managed. Unlike traditional infused oncology medications, which are administered in a clinical care setting and billed through the physician practice’s buy-and-bill program, oral oncology medications are typically dispensed by the specialty pharmacy directly to the patient to self-administer at home.

When it comes to oral oncoloytics, small deviations from ideal dispensing and dosing can have enormous consequences. For instance, “in chronic myeloid leukemia, as little as one week off of the prescribed oral oncology medication can cause the disease to relapse, so patients must take a pill without fail, every day, for the rest of their lives,” explains Ann Steagall, BSN, RN, OCN, Director, Clinical Policy for Biologics, Inc., McKesson’s specialty pharmacy. ‘That’s a lot to ask of patients—especially when you consider the potential financial implications or side effects they may be facing—but there’s so much at stake if they fall off therapy. High-touch support programs that involve regular outreach from a nurse help to not only encourage patient compliance, but provide a mechanism to quickly recognize the emergence of contributing factors such as pill fatigue, financial impediments and other lifestyle or health issues that may arise, so that rapid intervention from a nurse or pharmacist can be provided.”

“Meanwhile, as the cancer-treatment paradigm moves from infused therapies toward oral medications, oncology practices often lose money with that prescribing choice (as the oral oncolytics are not administered onsite nor billed through the practice’s buy-and-bill model). As a result, many oncology practices do not invest a lot in the extra programs or personnel to carry out high-touch patient support — rather, that tends to be relegated to the drugmaker-sponsored specialty pharmacy,” continues Steagall.

When the specialty pharmacy accreditation movement really began to gain traction several years ago, first movers were able to tout their hard-won accreditation status as a differentiator to set them apart from others competing for the same lucrative contracts with specialty drug manufacturers. However, as specialty drug makers, payers and pharmacy-benefit managers (PBMs) are increasingly urging — if not outright requiring — third-party accreditation from one or more of the leading accreditation bodies, this once-voluntary undertaking now feels more like a de facto requirement than ever for specialty pharmacy.

“Of course, specialty pharmacies should recognize that gaining accreditation benefits their practice and their patients,” says Bonome of URAC. “But we also see that many pharmacies come to us because a given drug maker or payer has made accreditation a requirement to do business within their limited-distribution network.”

Payers, in particular, have a lot of skin in the game whenever it comes reimbursing for high-cost specialty medications, which can easily cost $100,000/year or more. “When these therapies are administered and used properly, they can provide critical relief of symptoms, or even a cure, for patients, and that justifies the cost,” says Bonome. “Payers are also aware the improper use of these medications can lead to a worsening of the condition, which could lead to hospitalization and other high-cost interventions.”

“Importantly, the accreditation award reduces the burden of oversight by payers themselves, because it establishes specific, rigorous performance standards and then provides a consistent level of assurance (by the third-party accreditation organization) that the quality of services provided specialty pharmacy meets them,” says Osborne of Express Scripts, who adds that increasingly, accreditation is also required to meet regulatory requirements for government payers such as Medicare and Medicaid.

Meanwhile, in this era of value-based care, payers are also working with specialty pharmacies to create payment models that reward those specialty pharmacies that are able to demonstrate consistent patient outcomes and other performance metrics. While simply having accreditation no longer provides the degree of competitive differentiation it once did, the ability to deliver world-class programs and to develop the metrics needed to prove it can continue to give accredited specialty pharmacies a competitive advantage.

“Fortunately, any additional expenses and effort associated to gain and maintain accreditation can be justified by the potential to win or lose contracted work based on being able to demonstrate the accreditation status,” says Quintin Jessee, RPh, DPh, an executive at D2 Consulting, adding: “Today, if your organization is not accredited with any of the major players, you could instantly lose out on future business-growth opportunities.”

“Of course if you don’t have your house in order, you won’t be able to deliver the highest-quality care for patients with these complex illnesses, and you won’t be able to compete against those specialty pharmacies that do,” adds Mahaney on behalf of CPPA, who also served as the Executive Director of CPPA until late 2016. “Accreditation helps ensure both.”

Balancing customization and standardization

Accreditation criteria involve standardized protocols, processes, data-gathering, documentation and reporting requirements for patient care related to:

* Securing insurance approval for the patient

* Improving time to first fill of the prescription

* Investigating options that may be available to reduce the cost of the medication

* Managing patient data (from initial assessments through ongoing follow-up assessments)

* Coordinating care and documenting the care plan

* Reconciling medications (to avoid potential drug-drug interactions)

* Reporting clinical outcomes, side effects and adverse events

* Ensuring proper handling of hazardous waste

* Carrying out staff credentialing and training (with proper documentation)

* Monitoring the performance of incoming and outgoing telephone-based interactions with patients (looking, at for instance, speed to answer calls, longest wait times, how many calls are abandoned and so on)

* Providing seamless access to nurses, disease specialists and behavioral coaches who can increase patient understanding and support the optimal use of the medication.

Jessee of D2 Consulting notes that emerging specialty pharmacies can benefit from the accreditation process by using these standards to both level the playing field with existing players in the space, but to also build a solid infrastructure, with rigorous, durable processes, right from the outset, which will establish a pathway for successful growth over time.

Toward that end, specialty pharmacies should look at the data gathering and reporting requirements not as a burden but as a tool for continuous improvement, adds Bonome. “If you are required to track and report multiple metrics, you should use these to identify negative trends that arise and respond quickly with a corrective-action plan,” she says.

It is important for specialty pharmacies “to have a commitment to ongoing innovation and improvement,” says Mahaney of ASHP. “If you’re going to just check the box, you’re missing the greater point here.”

“As our CPPA surveyors are working with specialty pharmacies to gain or maintain accreditation, they will not only make specific recommendations in writing how the pharmacy can become compliant, but they will also document the specialty pharmacy’s own best practice or points of excellence,” says Mahaney. “CPPA-accredited specialty pharmacies can then publicize these findings to differentiate themselves from their competitors as they work to gain access to the specialty manufacturer distribution channels.”

In that same vein, when a specialty pharmacy is able to develop a strong, data-driven story to demonstrate strong patient outcomes related to the optimal use of the therapy, it can also leverage that accomplishment to demonstrate the high quality of its service offering, says Bonome.

By way of example, Jessee of D2 Consulting, says: “Several pharmacies have carried out case studies that demonstrate that their management of therapies and patient outcomes are saving the overall healthcare system money, through proper formulary management for PBMs, prevention of side effects, reduction of hospital readmissions and more.”

Maintaining some freedom to customize the offerings

The various accreditation organizations are quick to point out that while they establish rigorous performance standards based on clinical evidence and industry best practices, the opportunity for a certain amount of flexibility and customization is always baked into the different frameworks. Consider, for example, the inherent variability among complex illnesses — from hepatitis C and HIV to hemophilia and cancer — and the landscape of specialty therapy options that are available to treat them. To develop and administer the most meaningful wraparound programs, accredited specialty pharmacies want some degree of latitude, to work closely with the drug manufacturer to decide which types of data and metrics are most relevant.

“URAC’s accreditation programs allow for innovation and encourage customization by empowering organizations to develop drug- or disease-specific workflows that align with their business model and patient needs, while still meeting accreditation standards,” notes Bonome.

Despite the benefits, and the overwhelming peer and professional pressure to seek accreditation, some pharmacies do still choose to forego accreditation. “I see this all the time,” says Jessee of D2 Consulting. “The fees are often the biggest obstacle for smaller pharmacies, and the financial and administrative burden can be hard to justify if the return on investment is not obvious.”

The added costs are both internal ones (to provide the required patient services and reporting adequately) and external (the fees for initial and renewal inspections and audits), notes Express Scripts’ Saunders. “For some specialty pharmacies, the cost of a particular required accreditation may simply outweigh the potential benefits of participating in a given network, based on the payer’s reimbursement schedule,” she says.

The proliferation of competing accreditation bodies in recent years begs two important questions — Is there enough differentiation among them to justify so many players in the space? And why must today’s specialty pharmacies endure the added cost, parallel effort and potentially redundant burden required to achieve accreditation with multiple organizations, and manage so many sets of rigorous process and protocols to maintain ongoing accreditation?

While there are certainly overlaps in the philosophy and requirements of each of the competing specialty pharmacy accreditation bodies, many stakeholders agree that there’s still room at the table for all of them. “Some of these groups focus on specific portions of the overall specialty pharmacy offering, by offering specific accreditation requirements for Home Infusion, Sterile and Non-Sterile Compounding, Wholesaling, Durable Medical Equipment, Prosthetics, Orthotics and Supplies (DMEPOS),” explains Jessee of D2 Consulting.

He adds: “ACHC and URAC don’t offer any accreditation for wholesaling operations, but NABP offers such an accreditation (called Verified-Accredited Wholesale Distributors; VAWD). In order to get a state wholesale license in Indiana, Wyoming and North Dakota you have to have a VAWD accreditation.” He adds: ACHC has something similar with Compounding and it is required by states, so you must gain that accreditation if you do any compounding operations, in order to obtain a state pharmacy license.” On the other hand, the State of Michigan recently mandated Joint Commission accreditation for compounding pharmacies in that state.

“There are differences in survey requirements, survey processes, customer focus and support, costs, reputation and industry standing, along with the rigor of their individual accreditation processes that would impact the choice between accrediting organizations and ultimately define the competitive landscape,” adds Saunders of Express Scripts.

“Many PBMs carry out periodic audits of specialty pharmacies to ensure compliance with contractual requirements. Fortunately, most of the common audit topics are already effectively addressed within the rigorous standards imposed by the third-party accreditation organizations,” says Jessee. He notes that if the specialty pharmacies are not staying compliant with their accreditation standards, they will likely not do well with these audits.

As for the reporting requirements set forth in the various accreditation standards, they are generally two-fold:

(1) Reporting to any to external stakeholders (such as the specialty drug manufacturer, various payers and PBMs), and

(2) Reporting to the accreditation agency, to both demonstrate ongoing compliance and help the accreditation body to develop performance-related metrics of its own.

For example, the various accreditation agencies require accredited specialty pharmacies to track and report, on an annual basis, specific metrics such as:

* Patient and healthcare provider satisfaction

* Quality-related events and medication errors

* Active patient volume being maintained according to patient-case-management protocols, by disease state

From the drug maker’s standpoint, one of the most important metrics relates to patient adherence to drug therapy, as this is the ultimate bellwether of how all of the various program elements are working. “The pharmacy is in a unique position to track key indicators, such as side effects, adverse events and adherence. Consistent, periodic monitoring can identify patients who are struggling with adherence to medication, and provide timely, targeted interventions that will help to keep the patient on the regimen as long as it is clinically appropriate,” says Bonome. “Evaluating how pharmacies are tracking and documenting individual patient adherence is something that we review regularly, by pulling individual patient files, whenever we conduct an accreditation review,” she adds.

1 Drug Channels Institute, 2018 Economic Report on U.S. Pharmacies and Pharmacy Benefit Managers, available at:

https://drugchannelsinstitute.com/products/industry_report/pharmacy/

Articles

Accreditation status is both an entry ticket and a competitive measure for specialty pharmacies to attract manufacturer attention

Specialty pharmacy accreditation — burden and benefit

The emergence of literally hundreds of oncology therapies and combination therapies in recent years provides hope for patients with cancer, and expanded options for oncologists. Ongoing breakthroughs in both biomarker-indicated therapies and immuno-oncology therapies provide cause for celebration throughout the oncology community. “Only about 10% of malignancies are currently treated using biomarker-directed therapies, but that number is likely to rise exponentially in coming years, and this is adding complexity to patient-selection and decisionmaking for all stakeholders,” says Bruce Feinberg, DO, VP and Chief Medical Director for Cardinal Health Specialty Solutions. In particular, the development of clinical pathways, driven by medical researchers plumbing health outcomes data for best practices, combined with pharmacy benefit managers (PBMs) and insurers evaluating the economics of cancer care, is becoming more fraught.

Clinical pathways in oncology aim to create a useful, evidence-based framework to help oncologists make sense of the complex choices available, and to help enforce, where possible, a certain amount of standardization in cancer care. The goal is to focus prescribing efforts — in terms of optimal sequencing and timing of diagnostic testing and treatments, and optimal medication selection — favoring those choices that present the strongest clinical evidence as it relates to efficacy, safety and cost-saving opportunities. Clinical pathways committees typically review all of the available, up-to-date clinical evidence (such as clinical practice guidelines, peer-reviewed journals, scientific media, Medicare compendia, FDA labeling indications and so on) when devising their pathways protocols.

According to ASCO’s Task Force on Clinical Pathways, the four leading oncology pathways that dominate the scene in the US (in no particular order) are provided by:

* Anthem/AIM Cancer Care Quality Program (AIM)

* New Century Health, a specialty-care advisory firm

* Value Pathways by McKesson, USOncology Network and the National Comprehensive Cancer Network (NCCN)

* Via Oncology (which was acquired by Elsevier in January 2018)

“Pathways typically incorporate complex, regularly updated information related to disease staging, line of therapy, histology, driver mutations and protein expression and typically present it in a decision-tree logic to support the oncologist at the point of care,” explains Janet Serluco, MS, VP, Payer Access Solutions and Oncology Lead at Precision for Value, specialists in payer marketing.

“Clinical pathways take into consideration all the different treatment options available and narrow them down into a succinct list of choices that drive the most value, which is simply defined as the best possible outcome at the lowest cost,” “Oncology pathways are needed more than ever today with ongoing advances in precision medicine,” says Marcus Neubauer, M.D., Vice President and Medical Director, Payer and Clinical Services, McKesson Specialty Health. “Consider a busy oncologist trying to keep track of new cancer-causing mutations and the rapid entry of new cancer drugs to market. Pathways serve as guides through this much more vast and complex space.”

In recent years, a growing number of oncology practices and insurers have adopted (and even mandated) use of pathways. Oncologist use of clinical pathways (OCP) has reached 58%, according to a recent article in JAMA Oncol. [1] The American Society of Clinical Oncology (ASCO) reports a 42% increase in the number of oncology practices reporting compliance with a pathways program from 2014 to 2016. [2]

Meanwhile, an estimated 60 individual health insurance plans in the US have mandate the use of a particular oncology pathway — representing more than 170 million individuals, according to ASCO. To ensure and measure physician compliance, health plans typically use a carrot-and-stick approach, offering a mix of incentives such as increased reimbursement rates for medical procedures and medications, and reduced administrative requirements (such as burdensome prior authorization and step therapy protocols) when treatment is carried out within the proscribed pathways, notes Serluco.

To increase their utility, today’s competing oncology pathways typically offer various types of decision-support tools and software, and some are able to flow directly through the oncology practice’s chosen electronic health records (EHR) system, so the information is readily available within the physician’s workflow at the point of care. When the oncologist enters clinical data into a patient’s medical record, the EHR system flags a clinical pathway that is appropriate for the patient’s set of circumstances and provides relevant prompts for the physician. When a physician goes “off pathway” or chooses not to follow a clinical pathway for legitimate medical reasons, the EHR system will ask the oncologist to select and document the reason for doing so.

In addition to improving clinical outcomes and containing costs, adherence to pathways benefits oncology practices in other ways, says Neubauer of McKesson:

Contract leverage with payers. By adhering to the required oncology pathway and aligning incentives with the payer, the oncology practice benefits from lower operating costs and less administration hassle for both the prescriber and office staff.

Reduction in drug-inventory costs and cash flow. Oncology practices typically rely on the buy-and-bill model, whereby they purchase and inventory oncology therapy options and are reimbursed after they administer the drugs to patients. “Rather than ordering and storing the full range of potential medications for patients, practices can order and store only the medications they use most, based on their clinical pathways, and when they do, reimbursement for very expensive drugs is rarely declined,” says Neubauer.

Increasing clinical trial enrollment. The ability of today’s oncology pathways to embed details about available clinical trials directly into the decision-support tools provides an important advantage for both oncologists and patients. “Currently only 3% of adult cancer patients participate in randomized controlled clinical trials and those who do are younger, healthier and less diverse than their real-world counterparts,” notes Cardinal Health’s Feinberg.

While many stakeholders agree that the concept of oncology pathways is sound and has already proven to be effective in recent years, opportunities for ongoing improvement exist. Today’s pathways publishers are all grappling with how to effectively incorporate treatment options that aim to provide increasingly personalized care, based increasingly on the specific genetic nature of each patient’s malignancy and other clinical and socioeconomic factors. Similarly, pathways are being modified with the addition of biomarker-directed therapeutic options.

“Many people still think wrongly that oncology pathways are these broad, simple statements that aim to put all patients into the same lane,” notes Kathy Lokay, General Manager of Via Oncology. “To the contrary, they are actually very precise tools, and are becoming even more so, as more biomarker-approved indications keep coming to market.”

“Today’s pathways are already asking about a number of actionable biomarkers that were not being asked about even just a year ago, so they are evolving rapidly and that’s good news,” adds Robin Zon, MD, FACP, FASCO, Senior Partner, Michiana Hematology Oncology, and Chair of the ASCO Pathways Task Force.

“If we don’t continue to keep up with these discoveries, our pathways will become irrelevant,” adds Neubauer of McKesson.

While oncology pathways aim to streamline and focus the clinical information for oncologists, they also provide added administrative burden and workflow interruption — especially because most oncologists must adhere to multiple, parallel pathways programs, because different insurers mandate the use of different progams, and the oncology practice may have adopted or developed its own oncology pathway as well. The oncologist needs to move seamlessly among several competing pathways programs from during the course of every day is antithetical to the idea of streamlined efficiency, and this begs the question: How many is too many and is consolidation among today’s oncology pathways inevitable?

“Many prescribers report feeling overwhelmed by the intellectual, ethical and administrative burden they face, as they are forced to embrace numerous similar-yet-different pathways programs— and move seamlessly among them at the point of care — depending on which private or government insurance plan is held by every single patient who walks through the door, hour by hour,” says oncologist Zon.

While all of the competing pathways are developed from the same general body of clinical evidence, they do not necessarily offer identical treatment protocols or cookie-cutter recommendations. “Each of today’s competing oncology pathways varies in how comprehensive and restrictive the options are, what compliance thresholds are used, what level of evidence that will be accepted, the role of real-world data, and more,” says Feinberg of Cardinal Health.

“Without head-to-head comparison trials for most drugs, it’s like comparing apples to oranges. It requires a lot of nuanced involvement from the experts on the pathways committees and this leads to inevitable differentiation among today’s competing oncology pathways,” adds Lokay of Via Oncology.

“Today’s oncology practices must routinely support multiple pathways depending on their practice choices, institutional protocols, and payer preferences related to their patient coverage mix in terms of working within the patient’s insurer-preferred pathway,” explains Serluco of Precision for Value.

In general, oncologists tend to favor those those pathways that preserve more latitude in prescribing. With more latitude, the oncologist is then able to factor in other considerations, such as the cost burden for the patient (based on available coverage or copay burdens), co-morbidities, or socio-economic factors (such as access to transportation) that may or may not enable them to show up for weekly chemotherapy treatments. The level of reimbursement from payers for drugs that an oncology practice has purchased can also be a factor.

“Some practices report that they must be able to abide by four or five different pathways, and for any given patient, they must use the pathway that is promoted by that patient’s insurance plan,” says oncologist Zon. “As a community, we must find ways to reduce this burden for oncologists.”

“Given this added complexity, there is likely to be consolidation over time because it is a lot of work to develop and maintain them and markets tend to become more efficient when there is less duplication of effort in both the development and the use of oncology pathways,” adds Lokay.

“It is possible that NCCN, ASCO and others may eventually align with a consensus universal pathway, in which case vendors will be differentiated by their technology solution rather than their content,” adds Feinberg of Cardinal Health.

While the rise in oncology pathways use is providing demonstrable benefit to both payors and patients, it can also create barriers for pharmaceutical manufacturers, by limiting patient and provider access to therapies don’t make the cut. If an existing or newly approved oncology therapy option is not incorporated into one or more of the published pathways, the drug’s ability to gain traction in the market will be hampered, and may also engender less-than-favorable reimbursement terms from private and government insurers.

Today’s pathways-development committees all strive to maintain independence and autonomy, so the extent to which pharma manufacturers can influence the pathways-development process is limited and the pathway committees are very strict about the type of information drug companies can submit for consideration. For these committees, there is very little room for drug developers to plead their case, outside of the strict confines of evidence published in peer-reviewed journals and presented at peer-reviewed meetings, says Lokay of Via Oncology, adding: “To let anything else in opens the floodgates and it could be problematic.”

“We strive to keep free from bias and make our pathways decisions based on efficacy, toxicity and cost differences (the clinical facts). In order for our pathways to be respected by providers and payers we can’t show favoritism to one pharmaceutical company. If one company’s drug is in the same class as another’s, it usually comes down to price differences. However, most companies price their drug similarly to their competitors’ products, so we don’t even have much wiggle room there,” adds Neubauer of McKesson.

Nonetheless, industry observers agree there are still some strategies pharma companies can adopt to increase the likelihood that their drugs will be recognized within the leading clinical pathways. For instance, Lokay notes that in the absence of head-to-head clinical trials for most oncology medications, pathways committees are often left to “compare apples to oranges” when trying to interpret the findings and identify which treatment protocols will make the cut,” and this leaves room for improvement.

To further illuminate some perhaps-less-obvious benefits or distinguishing characteristics of their therapeutic options, drug manufacturers should strive to develop ongoing real-world evidence, and present or publish it in peer-reviewed journals and meetings. The ability to demonstrate, for instance, safety, tolerability or ease-of-administration advantages over competitor products in the same therapeutic space using real-world evidence may provide added insight for the pathways committees.

“The onus is really on pharma companies today to demonstrate that their product is not only safe and effective in the real world, but has favorable or justifiable cost implications in the populations payers are covering,” says John J. Doyle, SVP & General Manager, Real-World & Analytic Services, IQVIA, and faculty member, Department of Epidemiology, Mailman School of Public Health, Columbia University. “Without that, they are unlikely to be placed favorable in competing clinical pathways.”

Similarly, when drug makers are able to devise innovative contracting strategies that can bring down the cost of the care—for instance, data that confirm reduced hospital admissions related to the use of the therapy—such insight can also help to position the drug more favorably in the eyes of the pathways committees.

Going forward, Lokay also suggests that drug developers should also strive for improved clinical trial design — with closer collaboration with pathways developers. “This can help drug makers to develop the most appropriate evidence right from the outset — clinical evidence that showcases some specific competitive advantage for the investigational therapy against the therapies and treatment protocols that represent the existing standard of care.”

“Drug makers working to launch new therapies must be cognizant of the current state of the existing oncology pathways,” adds Doyle of IQVIA. “If you’re aiming to be incorporated into an existing pathway, you should be modeling what the implications would be of including your product in terms of overall costs and outcomes.”

“Sometimes even the ‘best therapy’ doesn’t work for all patients, so if your drug can meet the needs of a specific subset of patients and show improvement over the competitor’s drug (in terms of the route of administration, tolerability, side effects) then you’ll have a better chance of making it into the oncology pathways,” says Lokay.

Traditionally, tumor location has been the primary driver of treatment choice in oncology, and all of the current oncology pathways are organized according to the affected organ system, such as lung cancer, breast cancer, colorectal cancer and so on.

However, the May 2017 FDA approval of Merck’s Keytruda (pembrolizumab) as the first so-called “tissue-agnostic” oncology agent was a watershed event, demonstrating an important proof-of-concept and ushering in a new era in cancer care. Keytruda was granted accelerated approval as a tissue-agnostic oncology agent for the second-line treatment of adult and pediatric patients who had “microsatellite so-called instability-high” (MSI-H) or mismatch repair deficiency (dMMR) solid tumors — irrespective of tumor histology. “Keytruda’s MSI-H and dMMR approval blew open the doors, proving you could get a drug approved across multiple tumor types by using the ‘basket’ clinical trial approach, and that has now become a viable registrational strategy to pursue a tissue-agnostic drug approval,” says Jillian Godfrey Scaife of Trinity Partners, who co-authored a 2018 study and paper that surveyed the landscape in oncology basket trials currently under way. [3]

Trinity Partners’ study evaluated 37 ongoing basket trials in oncology involving 31 unique oncology therapies and 16 different biomarkers or genetic mutations. Two therapies are far enough along to be considered registrational (meaning they are clearly pursuing a tissue-agnostic regulatory filing): arotrectinib (LOXO-101, co-developed by Loxo Oncology and Bayer) and entrectinib (co-developed by Ingyta, Inc. and Roche). Nine others are potentially registrational, and the remaining 26 are exploratory, according to the study. “The process by which Keytruda gained approval provides a template for how these more exploratory trials could lead to tissue-agnostic approvals in the future,” says Scaife of Trinity Partners, and one of the report’s co-authors. “We expect the results of these trials, could lead to further registrational trials the years to come

Widespread genomic testing — the great enabler

There is no little irony in the fact that, as pathways become more personalized, the healthcare system is dealing with resistance to the genetic and biomarker testing that makes this personalization possible. Many physicians note that payer failure to cover the costs of comprehensive genomic testing, and the need for greater education to understand and interpret the output of such testing, stand out as a major barrier to broader adoption. Ongoing efforts to commercialize newer, less costly molecular diagnostic testing methodologies are also expected to help oncologists be able to more effectively match biomarker-directed and tissue-agnostic therapies to the right patient sub-populations over time.

“Integration of regular, comprehensive genomic testing will be essential to allow oncologists to quickly identify patients who may benefit from newer tissue-agnostic oncology agents and thus enable this new paradigm shift to take hold meaningfully,” says John Doyle, IQVIA. “Once next-gen tumor sequencing reaching the tipping point where a comprehensive panel is routinely run for most patients (and not just in an academic oncology setting to support clinical trials), then the full promise of this new approach will be realized in cancer care, in terms of being able to enroll more patients in tissue-agnostic clinical trials, and helping oncologists to quickly identify patients with actionable biomarkers once more tissue-agnostic therapy options are approved.”

“Maybe at the end of the day we have to rethink the way we describe oncology pathways. Perhaps ‘standardization’ is not the best word. It is more accurate to describe it as a precision medicine-management tool — delivering the right drug to the right patient at the right time,” says Zon.

1 JAMA Oncol. 2018;4(2):255-257. doi:10.1001/jamaoncol.2017.4473; https://jamanetwork.com/journals/jamaoncology/article-abstract/2666756?redirect=true).

2 ASCO’s State of Cancer Care in America 2017 report (LINK)

3 Trinity Partners, Oncology Basket Trials: An Emerging Paradigm Shift in Trial Design & Treatment Approach? http://www.trinitypartners.com/index.php/case-studies-examples/oncology-basket-trials-whitepaper

The flood of new oncology drugs is challenging the ability of healthcare providers to determine best treatment choices