The Iron Woundologist

  At a recent speaking engagement, I reminisced over the thousands of photos of dripping, ulcerated, puss-filled wounds I have shown at dinner meetings, demonstrating the less aesthetic side of my craft. In my experience, the wound care clinician is unperturbed by decomposing necrotic flesh even while cutting into the most underprepared meal. I have jokingly suggested that the Food Network® host a show featuring recipes in wound care: The Iron Woundologist.

  But I don’t want to distract you by humor born out of frustration. We may truly need a cookbook for wound care. At a recent national meeting, David Margolis presented his analysis of Medicare’s data on diabetic foot ulcerations and amputations and I was amazed to learn that one of the major independent risk factors for amputation is where in the country you reside. Physicians across the United States are clearly not following a consistent evidence-based standard of care, even though evidenced-based recommendations, such as the Wound Healing Society guidelines, are readily available. Undoubtedly, there is a need for clinician education on chronic wound care and limb preservation. Another important component is that there is a dearth of compelling evidence in our field, in particular, evidence on the comparative effectiveness of various interventions and treatments.

  Most of the evidence in wound care is derived from randomized controlled l trials (RCT) conducted by industry for product approval. These studies are designed by the sponsor in order to demonstrate whether a particular product or intervention is efficacious under very controlled conditions. We have learned a great deal from these trials and we owe our industry partners a debt for this data. I am persuaded that these commercial enterprises must continue to take an interest in the wound care marketplace; however, many trials and tribulations are inherent in carrying out these studies. I have experienced all the “trials and tribulations” possible in such studies, and I have summarized them in Table 1.

Table 1. Trials and Tribulations

  1. The minute you agree to participate in a clinical trial all of your potential patients will go away.

  2. If the sponsor promises that the trial will begin no later than two months it will begin in six months or longer. In the interim, the sponsor and Contract Research Organization (CRO) will harass you for every document from first grade on, then upon receiving them disappear.

  3. If the sponsor is too cheap to pay for an investigators meeting they will not pay you enough for the trial.

  4. The monitor will attempt to schedule a qualification visit at the most inopportune time (they won’t make a qualifying visit if you are not going to qualify).

  5. If you like your Clinical Research Associate (CRA) (monitor) you will never see him/her again.

  6. The budget, no matter how large, will never cover all of the hidden costs.

  7. If there are more than 30 exclusion criteria, you will not be able to enroll a single patient.

  8. Enrollment is inversely proportional to the number of exclusion criteria.

  9. The day your IRB approves the protocol Investigator’s Brochure and Informed Consent the sponsor will mail out the first amendment.

  10. If there are more than 7 amendments, the trial will fail.

  11. On the busiest day in your clinic the camera will fail and after changing the batteries three times the camera company will tell you it is broken. The lab tech will then put all of the “do not freeze” items on dry ice and the patient you enrolled yesterday will have a major SAE.

  12. All computerized records crash.

  13. There are no compliant patients.

  14. The lab company will send the wrong tubes, supplies and syringes at least once.

  15. During the course of the trial: You will put the right specimen in the wrong container and you will put the wrong specimen in the right container.

  16. The shipping company will make the last pick up an hour before you draw the specimen.

  17. If the protocol requires the wound not to heal by more than 30% in the first two weeks of screening, it will close 50% after making no progress for 5 years.

  18. The source documents will omit an essential data collection point. You will discover it after your quota of patients has been enrolled.

  19. The monitor will make a change to the CRF against your better judgment, which will generate thousands of Data Clarification Forms (DCFs).

  20. The sponsor will complain about enrollment throughout the length of the trial. They will schedule numerous teleconferences which will do nothing to assist enrollment but will prevent your study coordinators from seeing potential patients.

  21. The happiest days in your research life will be the day you enroll the first patient in your trial and the day you enroll your last.

  In addition to the above frustrations, there are a number of serious limitations in the methodology used for wound healing RCTs. These limitations have been addressed by the Alliance of Wound Care Stakeholder’s Panel on Wound Care Evidence-Based Research (POWER™). Using a Delphi process 115, thought leaders in wound care reached consensus on 19 principles for conducting clinical research in wound healing. It was presented at the Symposium on Advanced Wound Care (Table 2).

Table 2. 19 Principles for Conducting Clinical Research in Wound Healing

  1. There is a need for a guidance document in the field of wound care research.

  2. Wound care researchers, product developers, manufacturers, policy makers, payers, clinicians, and consumers should be educated on wound care research guidelines.

  3. All human wound care research conducted in the United States should follow the principles of Good Clinical Practice (GCP) in accordance with FDA regulations.

  4. The study design of research conducted in wound care should be matched to its purpose.

  5. Wound care clinical research should include evaluation of simultaneous and/or sequential interventions when appropriate.

  6. Wound care research should incorporate a multidisciplinary approach whenever possible.

  7. Research design should include parameters that are appropriate for the type of the study.

  8. Primary endpoints in wound care research need to reflect both the goals of the intervention and clinical practice.

  9. Study design should be reviewed.

  10. Study design should be open to amendment.

  11. Quantitative wound care studies should include a run-in period as part of the initial assessment when it is appropriate.

  12.The rationale for inclusion and exclusion criteria in wound care research should match the goals of the study but the generalizability of the results to wound care populations should also be spelled out.

  13. Highly vulnerable populations are under-represented in clinical wound care research practice and should be included where feasible.

  14. The definitions for intervention(s) provided to the comparator groups in any clinical study, typically defined as “moist wound care” or “usual care,” need to be explicit.

  15. An appropriate but comprehensive data set should be included in the research design to describe the participants.

  16. An appropriate but comprehensive data set should be included in the research design for any study that involves wound evaluation.

  17. Clinical wound care research should include rates of recurrence where feasible.

  18. National or formal wound registries should be developed with real-world data collection.

  19. Cooperative groups, composed of multiple researchers working in concert, should be formed in order to facilitate and optimize wound care research.

So Who Will Perform Wound Care Research and How?

  Woundologists working in all care settings have an obligation to contribute to clinical trials. In fact, I am convinced that in order to be a “center of excellence,” research must be a part of a center’s offerings. There are several general approaches to starting a program in the wound clinic. One method is to partner with a management company or an established center that provides support for research as part of its services: training in good clinical practices (GCP) and investigational techniques, introduction to upcoming clinical trials, central regulatory support, and on-site assistance during the conduct of a trial. Alternatively, the center can launch a program independently. This approach is best suited to academic centers with established research infrastructure.

  However, RCTs are limited not only in terms which facilities may be best suited to perform them, but in the applicability of their results. Because of their strict exclusion criteria, it is estimated that more than 75% of patients seen in wound centers would have been excluded from all of the RCTs performed on wound care modalities in the past ten years.1 Thus, there is an overwhelming need for alternative types of investigation, such as registries and prospective observational studies. The recent success of the American College of Hyperbaric Medicine’s registry on the use of hyperbaric oxygen therapy in the treatment of radiation injured tissues is one example of the type of research that can be performed through cooperation between wound and hyperbaric centers. This registry has collected data from more than 2000 patients demonstrating the effectiveness of HBOT in soft tissue radionecrosis.

  The Federal Coordinating Council for Comparative Effectiveness Research has recommended that “longitudinal linked electronic health record (EHR) databases or patient registries’ are a major area of investment for CER research.” (www.hhs.gov/recovery/programs/cer/cerannualrpt.pdf) In other words, it is possible to use data collected in the course of regular clinical care and use it to perform comparative effectiveness research. The U.S. Wound Registry, sponsored by Intellicure, has done this and published several papers using this method.

  The POWER principles can provide some much needed guidance for the design of future wound care clinical trials. In the mean time, we encourage all wound care clinicians to approach patients with much the same attitude as an oncologist, as though they were each part of an established “treatment protocol,” (to improve basic care and interventions) and contributing data to some type of registry.

Dr. Thomas E. Serena, MD, FACS, MAPWCA, FACHM is the founder and CEO of the Serena Group™ family of companies operating wound and hyperbaric centers across the United States, providing point-of-care services for nursing facilities, managing inpatient wound care teams, and consulting for more than two dozen industry partners worldwide.

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. 22:316-324, 2009.