Keeping ‘Skin In The Game’ for the Quality Payment Program

The future of CTP utilization in wound clinics could hinge on the development of CTP outcome measures and quality reporting practices of today’s clinicians.

As all wound care practitioners know, new cellular and/or tissue-based products (CTPs) seem to become available each month. Knowledgeable sales representatives from various manufacturers arrive to the wound clinic with information about clinical trials performed with their products and tout their superior efficacy over competitors. However, the fine print is that these trials demonstrate efficacy under ideal conditions, targeting relatively small and superficial ulcers among patients without any serious comorbid conditions. When the exclusion criteria of these trials are compared with comorbid conditions that affect real patients, more than half of the “real-world” patients living with chronic wounds would have been ineligible for participation in the majority of cellular product randomized controlled trials (RCTs).¹ Payers then craft coverage policies for CTPs based on the exclusion criteria of these trials, denying coverage for CTPs in the majority of real-world patients based on the argument that their effectiveness among such compromised individuals is unproven. In other words, if the clinical trial excluded patients living with arterial disease, the payer denies coverage of CTPs to a patient who has any arterial insufficiency. If the trial excluded patients with autoimmune disease (eg, lupus, rheumatoid arthritis), the payer doesn’t cover CTPs in those patients either. While it is true that we do not know the effectiveness of CTPs among the patients who need them most, there is, in fact, a much more serious problem than lack of information. When clinicians use CTPs on patients who may need them but for whom the applicable Medicare Administrative Contractor has issued a local coverage determination specifically excluding them, they (and the hospital) are at risk of monetary recoupment. Physicians have been audited for using CTPs outside of these coverage criteria and have paid back money to the Centers for Medicare & Medicaid Services (CMS) — with penalties. When this happens to the physician, payments may also be recouped from the hospital (and vice versa). The “nongeneralizable” design of CTP clinical trials affects more than simply our knowledge base about them: It affects payment, coverage, and the very future of this therapeutic category. 

Harnessing Real World Data on CTPs 

Prospective trials need to enroll more serious wounds and sicker patients with common comorbid diseases. Understandably, manufacturers are afraid to design trials like this because healing rates in those trials will be lower than previously observed, and no company wants to be the first to do such a trial. Manufacturers might not even be able to show that their product works at all, which could spell financial disaster for the company. Since these types of trials are not likely to happen anytime soon, we can learn a lot about the effectiveness of CTPs in real-world patients by retrospectively analyzing data from the clinical use of these products. It might even be possible to use clinical data to expand their indications for use. The U.S. Food & Drug Administration has drafted guidance on the use of real-world data in regulatory decision-making that might provide a path forward for expanding the indications for the use of CTPs to more serious wounds or more compromised patients.² Unlike a prospective trial, which is designed to control key variables, there are many uncontrolled variables in the real world related to patient severity, treatment interventions, usual care, and quality of documentation. Prior to the widespread adoption of electronic health records (EHRs) harnessing real-world data for any aspect of regulatory decision-making would have been unlikely. However, it is now possible to control the method of documentation, stratify sick patients using mathematical models, and standardize usual and customary care through “point of care” reminders in the EHR known as “clinical decision support” (CDS). The result is a repository of data on treatment effectiveness that can enhance and even help design future prospective trials.³ 

A recent article describes a network of wound clinics engaged in clinical research that is linked through a wound care-specific EHR that offers CDS tools and facilitates quality reporting.⁴ Clinical practice suggestions developed using the Wound Healing Society’s clinical practice guidelines⁵ drive success with quality measure performance based on a suite of wound care-relevant quality measures developed by the U.S. Wound Registry (USWR).⁶ Clinicians are reminded at the point of care to conduct diabetic foot ulcer (DFU) offloading, venous leg ulcer (VLU) compression, and arterial screening (as only a few examples). The details of CTP application are highly structured and all of the patient’s medications and comorbid diseases are recorded as structured data. Practitioners can obtain credit in the Physician Quality Reporting System and the Merit-Based Incentive Payment System (MIPS) for reporting wound care-relevant quality measures.⁷ Behind the scenes, the Wound Healing Index (WHI)⁸ is embedded into the EHR, calculating the mathematical likelihood of a given wound healing and enabling the creation of matched cohorts for either prospective or retrospective research with patients of varying levels of illness. This integration of real-world clinical care with quality improvement, linked to the CMS Quality Payment Program (QPP) reporting requirements, drives the capture of high-quality, structured data for comparative effectiveness research. Currently, 12 facilities in nine states have adopted the consortium’s network EHR. These facilities provide an opportunity to compare the differences between real-world patients receiving CTPs and the subjects enrolled in the prospective trials that brought some of these CTPs to market while providing a better understanding of why we have a problem.⁹

What “Real” Patients Look Like

Among the recent RCTs performed by the research network, a total of 196 subjects with VLUs were enrolled in two trials. In contrast, there were 856 patients living with VLUs seen in those clinics (a total of 1,943 ulcers). VLU patients had an average of more than 2.2 wounds per person, although the VLU trials only enrolled one wound per patient. The real-world patients were a decade older than the subjects enrolled in the VLU trials, with 65% of real-world patients being 65 years or older compared to only 39.3% in the RCT. In reality, 14.1% of patients lived with peripheral arterial disease and 15.5% lived with congestive heart failure, conditions that were excluded in the RCTs. Astoundingly, the mean size of the real-world VLUs was more than five times the size of the VLUs enrolled in the RCTs. The exclusion criteria of the RCTs were used to estimate the predicted likelihood of healing (average WHI) among the VLUs enrolled in the RCTs and found it to be 75.9. In other words, the majority of VLUs enrolled in the CTP prospective trials could have been predicted to heal even without the CTP. In contrast, the average WHI of real-world VLUs was only 69.3. The contrast between real-world DFUs and the DFUs enrolled in cellular trials was even more dramatic. A total of 271 subjects with DFUs were enrolled in four RCTs (total of 244 subjects). Within those clinics were 1,047 patients living with diabetes (2,634 DFUs), 12.2% of whom also lived with renal failure, which was an exclusion in the trial. More importantly, 43.6% of real-world patients had ulcers that were Wagner Grade III or above, and their initial wound surface area was three times larger than the DFUs enrolled in the RCTs. The CTP trials enrolled only relatively small Wagner Grade I or Grade II ulcers, and their estimated likelihood of healing was 88.1, meaning, the DFUs in the CTP trial were highly likely to heal even without the CTP. By comparison, the average WHI of real-world DFUs was only 68.6. 

These numbers clearly show that real-world patients are older, sicker, and have serious comorbidities that are excluded from the CTP trials, not to mention that their wounds are bigger and more severe. Collectively, this is proof that the field of wound care is caught in a vicious cycle. RCTs exclude real-world patients and the result is that the evidence derived from these studies does not apply to real-world patients. Real-world data may offer a way out, however. The WHI could be the key to success because now that CMS has begun publicly reporting outcome data, the wound care industry can no longer continue to tout healing rates that are > 90% (which is only possible by not reporting all the patients who do poorly). Reporting such numbers makes it impossible to identify which patients really need advanced therapeutics. However, if a tool like the WHI predicts that the likelihood of healing a patient is, for example, < 60% on the day he/she is first evaluated, but he/she subsequently heals with a CTP, it is compelling evidence that the cellular product changed the outcome. The USWR hosts the Cellular and Tissue Based Therapy Registry listed on www.clinicaltrials.gov. A cursory review of the patients receiving CTPs in the real world suggests that the patients and their wounds are far more serious than those enrolled in the prospective trials that brought RCTs to market. The problem is that this means CTPs are being used outside of their coverage criteria.

The Future of CTPs & The Quality Payment Program

The USWR has tried to get CMS to support “process” measures like DFU offloading and venous ulcer compression, but Medicare dislikes process measures and is rejecting many of them. Although there is much talk about how, under the QPP, physicians will be paid on the basis of outcomes, this sentiment is not actually true unless there are wound care outcome measures available for wound care clinicians to report. Without the creation of outcome measures relevant to wound care practitioners, wound care practitioners can report only the quality measures CMS makes available, and those have nothing to do with wound care or cellular therapy. However, CMS will still evaluate practitioners on the basis of the “resource use” (one of the four categories on which their MIPS score is determined¹⁰) on their patients. In other words, the cost associated with these patients will be assessed, but not in relation to their outcome since there are no measures of their outcome. That is why the USWR has developed a risk-stratification system for wounds. If we do not create our own risk-stratified outcome measures through a qualified clinical data registry, then we cannot be paid on the basis of outcomes. Surprisingly, the manufacturers of cellular products have thus far not supported the development of the outcome measures that will be essential to ensuring the future use of CTPs. They will need to commit to the measure-development process soon, and clinicians will need to commit to quality measure reporting, which so far they have not done.

The USWR is also trying to help the field move in the right direction with an “appropriate use” quality measure for CTPs. Prior to applying a CTP, clinicians must have completed vascular screening, wound bed preparation, offloading, or compression (for example). Appropriate use quality measures help practitioners raise the bar on the use of advanced therapeutics and get their processes in place so that when the measure is combined with a risk-stratified healing measure, it’s possible to demonstrate the incremental benefit achieved from treatment with CTPs in relation to the severity of a specific wound given standardized routine care. However, that is still not enough. CMS is developing “resource use” measures that add up all costs associated with a certain procedure or diagnosis, enabling Medicare to assess the “spend” in relation to the outcome. Specialty areas of medicine such as cardiology, orthopedics, and oncology are also diligently developing sophisticated resource use and episode-based measures while the wound care industry continues to fabricate “just so” stories about healing rates. At some point, it will be necessary to admit that if we report on all of our patients we only heal about 66% of them, perhaps less.¹¹ 

A Plea to Our Industry

We need to conduct more generalizable trials if we are going to understand the effectiveness of CTPs among very compromised (but typical) wound clinic patients, so that we can determine the “spend” in relation to the achieved real-world outcome. If we as an industry do not do this, there is a future scenario in which physicians with a high utilization rate of CTPs experience a claw back of their Medicare Part B revenue because their resource use will be too high in relation to their quality scores (since there are no outcome measures for them to report that are relevant to cellular products). In truth, we may not need to worry about that scenario, which is still some years away, because we may find it difficult to provide CTPs long before that. If the CTP manufacturers do not initiate real-world clinical trials, or at least analyze currently available real-world data to expand their indications for use, we will not be able to provide CTPs to the patients who really need them. Medicare and private payers are already beginning to enforce the restrictions on coverage policy for CTPs that have long been in place but have previously been ignored. If we want our patients to have access to CTPs in the future, a lot of things will need to change. Manufacturers will need to design future clinical trials differently in order to obtain more relevant data on CTP efficacy and clinicians will have to commit to quality reporting in order to obtain useable data on CTP effectiveness. That is how we will keep “skin in the game” for the QPP. 

Caroline E. Fife is chief medical officer at Intellicure Inc.; executive director of the U.S. Wound Registry; medical director of St. Luke’s Wound Clinic, The Woodlands, TX; and co-chair of the Alliance of Wound Care Stakeholders. 

References

1. Carter MJ, Fife CE, Walker D, Thomson B. Estimating the applicability of wound care randomized controlled trials to general wound-care populations by estimating the percentage of individuals excluded from a typical wound-care population in such trials. Adv Skin Wound Care. 2009;22(7):316–24.

2. Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices: Draft Guidance for Industry and Food and Drug Administration Staff. FDA. 2016. Accessed online: www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm513027.pdf 

3. Institute of Medicine (US) Roundtable on Evidence-Based Medicine. In: Olsen LA, Aisner DL, McGinnis JM. The Learning Healthcare System. Washington, DC: National Academies Press (US); 2007.

4. Serena TE, Fife CE, Eckert KA, Yaakov RA, Carter MJ. A new approach to clinical research: integrating clinical care, quality reporting, and research using a wound care network-based learning healthcare system. Wound Repair Regen. 2017. Epub ahead of print.

5. Clinical Practice Guidelines. Wound Healing Foundation. Accessed online: www.woundhealingsocietyfoundation.org/programs/guidelines.aspx

6. 2016 US Wound Registry Measures For Reporting. USWR. Accessed online: www.uswoundregistry.com

7. MACRA. Centers for Medicare & Medicaid Services. Accessed online: www.cms.gov/medicare/quality-initiatives-patient-assessment-instruments/value-based-programs/macra-mips-and-apms/macra-mips-and-apms.html

8. Horn SD, Fife CE, Smout RJ, Barrett RS, Thomson B. Development of a wound healing index for patients with chronic wounds. Wound Repair Regen. 2013;21(6):823–32.

9. Clinical Research. Serena Group. Accessed online: https://serenagroups.com/node/11 

10. The Merit-Based Incentive Payment System: MIPS Scoring Methodology Overview. Centers for Medicare & Medicaid Services. Accessed online: www.cms.gov/medicare/quality-initiatives-patient-assessment-instruments/value-based-programs/macra-mips-and-apms/mips-scoring-methodology-slide-deck.pdf

11. Fife CE, Carter MJ. Wound care outcomes and associated cost among patients treated in US outpatient wound centers: data from the US Wound Registry. Wounds. 2012;24(1):10–7.