This video features an interview with members of the ECRI Institute-Penn Medicine Evidence-Based Practice Center (ECRI) and the Agency for Healthcare Research and Quality (AHRQ) regarding a systematic review of skin substitutes conducted by the ECRI at request of the Centers for Medicare and Medicaid Services.
For additional videos and to read a brief summary of the review, check out the Advances page here.
Transcript
Dave Snyder: Hi, I'm Dave Snyder, Senior Research Analyst and PhD at ECRI. I am part of our Clinical Evidence Assessment group, and I've been here for 23 years.
David Niebuhr: Good morning. My name is David Niebuhr. I'm a Medical Officer at the Agency for Healthcare Research and Quality, AHRQ, and specifically in the Evidence-Based Practice Center. Our mission is to transform healthcare by increasing the quality, availability, and use of evidence, via scientifically rigorous and unbiased analysis of the evidence. I'm trained in family medicine and public health preventive medicine. And I've been with AHRQ in the Evidence-Based Practice Center for a little over seven years now.
Jonathan Treadwell: Hello, everyone. My name is Jonathan Treadwell. I am the Co-director of the Evidence-Based Practice Center at ECRI. I've been at ECRI about 22 years, writing systematic reviews and doing meta-analysis. As co-director of the EPC, I do a lot of overseeing of the work that we are contracted to do by AHRQ, whether it is a technical brief such as the one you're about to hear about, or a systematic review. Thank you.
David Niebuhr: Well, I would just like to explain for the people watching this interview, that the AHRQ Evidence-Based Practice Center follows an extremely scientifically rigorous and transparent process. So in this case, this topic was nominated and sponsored by CMS. But once we have the topic nominated, we award it to one of our Evidence-Based Practice Centers under a master contract. In this case, to ECRI.
The process really begins with identifying stakeholders that are interested in the final report, the evidence review. And so these stakeholders are a mixture of private and public entities, professionals, professional societies, federal agencies, research funders, all interested, as I said, in this topic. And so we did that. We notified these stakeholders that this topic was commencing. The ECRI Evidence-Based Practice Center developed a protocol, and that protocol was published and publicly available, and then they prepared a draft report.
For all of our evidence reviews, including this technical ... this evidence report goes through a rigorous peer-review process from subject matter experts that are disinterested in the authoring of the review and revision to those comments. Then all of our evidence reviews go out for public comment. And in this case, and in all of our reviews, we sent out notifications that the public comments are open for this review to all the stakeholders I mentioned before, as well as the hundreds of people that we have in our AHRQ Evidence-Based Practice Center Listserv.
So then ECRI responds to each of these peer and public comments individually, and revises the report accordingly. Then that report is reviewed by AHRQ, and in this case CMS, and eventually is approved and posted publicly. So just to, in closing, just emphasize it's a very rigorous and transparent process. And we hope that that makes it of greatest value to the community of interest. Thank you.
This technical brief describes the various products commercially available in the United States that may be considered as skin substitutes. It examines the systems used to classify skin substitutes, and it identifies and assesses the clinical literature evaluating skin substitutes published since the 2012 AHRQ Report, Skin Substitutes for Treating Chronic Wounds.
AHRQ produces technology assessments for the Centers for Medicare and Medicaid services, or CMS, which uses them to inform its national coverage decisions for the Medicare program, as well as to provide information to Medicare carriers. Technology Assessments, or TAs, can influence Medicare eligible coverage, or actually no coverage, depending on decisions after reviewing the evidence. And in this case specifically, affect which skin substitutes are covered.
This particular Technology Assessment had the potential of having a large ripple effect in the coverage pond by influencing state and private health plans, as well as Medicare. In this case, CMS decided not to issue a national coverage determination for skin substitutes based on this technical brief, and instead allowed for local coverage decisions for skin substitutes by Medicare administrative contractors.
This technical brief prepared a map of the landscape of skin substitute products, potential ways to categorize skin substitute products, and important study design elements that will lead to the availability of future high-quality evidence for payers, physicians, and patients in their decision making.
Dave Snyder: Hi. As Dave just outlined, our clinical evidence review had four primary goals. To describe skin substitute products commercially available in the United States used to treat chronic wounds. To examine systems used to classify skin substitutes. To identify and assess randomized control trials. And to suggest best practices for future studies.
Therefore, our report asked these key questions. What products are commercially available in the United States that may be considered skin substitutes? What classification systems have been developed to categorize skin substitutes? What were the design characteristics and treatment outcomes in available RCTs examining skin substitutes to treat chronic wounds? And what best practices in study design could be used to produce high-quality evidence on skin substitutes?
Addressing the four main parts of the report, we found the following. We identified 76 commercially available skin substitutes to treat chronic wounds. The majority of these do not contain cells, and are derived from human placental membrane, animal tissue, or donated human dermis. Skin substitute classification systems categorize products according to cellularity. Whether they're acellular, without cells, versus those with cells. By source material, human animal or synthetic. And by which skin layers are to be replaced.
Included studies in our report were 22 RCTs and three systematic reviews, and ongoing clinical trials found during our search. We examined approximately 25 skin substitutes that actually had published reports. That's about 33% of the available skin substitute products. Available published studies rarely reported whether wounds recurred after initial healing. Studies rarely reported outcomes important to patients, such as return of function and pain relief. The large majority of studies examine diabetic foot ulcers. Future studies may be improved by using a four week run-in period before study enrollment, and at least a 12 week study period. They should also report whether wounds recur during six months follow up.
Diabetic foot ulcers were examined in all three systematic reviews and 15 RCTs, while venous leg ulcers were examined in only six RCTs, and pressure ulcers were examined and only one RCT, meaning we found only one RCT that used what we would consider a skin substitute to treat a pressure ulcer. Most RCTs compared skin substitutes to standard of care, which varied from study to study, and not other skin substitutes. They typically enrolled fewer than 60 patients per arm and measured outcomes up to 16 weeks.
Studies also had large variation between study arms for baseline need wound size and baseline wound duration. Using a 10 point risk of bias tool, 10 studies were rated moderate risk of bias, 12 studies were rated low risk of bias, and no studies were rated as a high risk of bias. This gives us good confidence in study results, but as noted above, studies could be improved. There are so few studies compared to the number of products on the market, and study results cannot be generalized across products.
Studies examining acellular dermal substitutes, this includes decellularized donated human dermis, human placental membranes, and some animal tissues, versus standard of care reported more effective, complete wound healing and shorter time to healing with acellular skin substitutes for diabetic foot ulcers and venous leg ulcers. Standard of care varied across these studies, which may have contributed to differences in outcomes.
Additional evidence from studies examining other skin substitute classifications versus standard of care and head-to-head comparisons of skin substitutes are necessary to establish whether any one skim substitute product is superior to another.
As mentioned above, the acellular products where the most studied and had favorable outcomes. However, studies rarely reported clinical outcomes such as wound recurrence, hospitalization due to infection, and amputations. Patient-related outcomes, such as functional capacity, pain, exudate and odor control were also under reported.
We were not looking to directly change clinical practice based on our report. Our purpose was to summarize the best available evidence, and identify any gaps in the evidence that could be filled by future research. The users of the report could help change clinical practice. For example, by prioritizing some treatments over others based on the evidence we summarized.
We found major gaps in the evidence space for venous leg ulcers, and in particular, pressure injuries. These are areas that could use further study.
The wide variation in study design, even among RCTs, limits the ability to compare outcomes across studies. Comparisons across studies may be enhanced by standardizing approaches for inclusion criteria, such as wound size, wound duration before study inclusion, and wound severity, by using a two to four week run-in period before study enrollment and a 12 week study period. Also, by reporting recurrence up to six months, as well as wounds healed during the study, and by blinded wound assessment. I want to emphasize that blinded wound assessment.
Patient inclusion criteria could be expanded to include patients more representative of clinical practice and of poor health in typical patients included in RCTs. This would allow sub-analysis of gender, race, ethnicity, age, and comorbidities that may help direct specific product use for different wound conditions.
I'd just like to say that ECRI, through its Evidence-Based Practice Center and its Clinical Evidence Assessment Group continues to review and assess skin substitute products used for treating chronic wounds. And through this assessment, I know that new studies are out there, RCTs and so forth. So there is lots of new information coming about skin substitutes and their use in chronic wounds.
