1. Niezgoda JA, Van Gils CC, Frykberg RG, Hodde JP. Randomized clinical trial comparing OASIS Wound Matrix to Regranex Gel for diabetic ulcers. Adv Skin Wound Care 2005;18:258-66. [Context Link]

2. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled double-blind study. Diabetes Care 1998;21:822-7. [Context Link]

In response:

We would like to thank Mr Magee and Dr Ovington for their interest in our article. We certainly agree that randomized clinical trials (RCTs) using scientifically sound study designs are invaluable to the wound care community. It was precisely for this reason that we conducted our study, a randomized comparison of treatments that permitted assessment of therapy effectiveness under comparable clinical conditions.

We provide the following comments in response to their critical analysis of our study, although most of these issues are addressed in the Discussion section of the article.

* Our study was designed as a noninferiority study and the results demonstrate that noninferiority was in fact achieved. We did not state that additional patients would respond in the same proportions as the patients evaluated; however, clinical intuition would generally support this likelihood. It is indeed the purpose of clinical studies to predict population responses. That is, the responses of a representative group of patients serve as the best predictor of responses in the broader patient population. Although we cannot conclude from this study that one treatment has a significantly higher healing rate than the other, we believe that increasing the statistical power of this study may have led to significant between-group differences, given the relatively large (19%) difference in healing rates observed with the two treatments.

* The study was designed to detect differences in product effectiveness while acknowledging typical variations in actual clinical practice patterns. Offloading techniques were allowed to reflect the practice standard of the individual site investigator. We are concerned by the inference that this distinction suggests that offloading was not performed or that practice standards at participating sites were substandard. Neither suggestion is true. Improved healing rates in the nonplantar wounds (40% to 47%) were noted in both treatment groups. These differences are not unexpected clinically when compared with healing in the more difficult plantar wounds; they do not typically reflect offloading techniques. The differences in efficacy rates with Regranex in the present trial (14% at 12 weeks) versus the Phase III trial (34%) cited by Mr Magee and Dr Ovington underscore the importance of comparing treatments within the same study.

* Once a product has been approved for clinical use, clinicians are not required to use it exactly as labeled in the prescribing information. Indeed, postapproval studies can provide valuable information about product effectiveness when used in a manner that is more accurately reflective of typical or usual clinical practice, and about alternate treatment regimens or indications. In the treatment of diabetic foot ulcers, rapid healing is advantageous from both patient quality-of-life and pharmacoeconomics perspectives. Twenty-week usage of any single modality is increasingly uncommon in current clinical practice settings. It is well known that if a treatment is going to be effective, it is more likely to be effective early after the initiation of therapy (as seen in the OASIS group). Based on these rationales, we selected a 12-week end point for our study. As a clinical study published in a peer-reviewed journal, ours was not obliged to state compliance with product labeling. Nevertheless, in the Discussion section, we do note healing rates at week 20 in the cited Phase III trial.

* Crossover and 6-month follow-up results are important variables in the treatment of chronic wound healing. We state clearly in the Results section that "no statistical analyses were performed with these data due to the limited number of patients evaluated." In the Discussion, we also state appropriate caveats: "The limited number of patients analyzed after 6 months necessitates further investigation into recurrence rates following treatment." We are confident that Mr Magee and Dr Ovington appreciate that significance canbe established and discussed only if statistical analysis is performed.

* As mentioned, "assessment of inclusion and exclusion criteria was based on available data at the time of enrollment." In 1 patient, the A1C level was later found to be elevated. According to best clinical practice and intent-to-treat analysis, this patient was not removed from the analysis because a full treatment regimen was given. Removing the 1 Regranex patient with the A1C level of 13.7 results in a healing rate of 28.6%.

We are pleased to provide further clarification regarding the published findings of our RCT. The results of our clinical trial are scientifically valid and clinically compelling. We are not surprised that our findings have caused certain corporate concern. We advocate and support the publication of unbiased clinical research.

Finally, we would like to state that none of the primary authors of our study needed to disclose that they were stockholders of the company sponsoring the study or manufacturing the product.

-Jeffrey A. Niezgoda, MD, FACHM, FAPWCA, FACEP

-Carl C. Van Gils, DPM, MS, CWS

-Robert G. Frykberg, DPM, MPH, FAPWCA

-Jason P. Hodde, MS

The Chair: Low-tech Device Helps Prevent Pressure Ulcers

Each day as I make my rounds in hospitals and nursing homes, I wonder why patients are in their beds so much of the time, especially in light of the prevalence of pressure ulcers among patients in all health care facilities. I think we are overlooking a simple device that can prevent more pressure ulcers than any high-tech specialized bed or mattress. It is called the chair.

Almost all pressure ulcers that develop in hospitals and nursing homes are on the sacrum, heels, or hips. It is very rare for a patient to develop an ischial pressure ulcer. Sitting in a chair will relieve pressure on the patient's most vulnerable areas.

I believe we must ask ourselves, "Are we really making the effort to get patients out of bed?" I have heard many health care professionals argue that if a patient has a sacral ulcer, he or she should not be sitting up in a chair or wheelchair because of pressure on the sacrum. However, sitting in a 90-degree upright position does not put pressure on the sacrum. If that were the case, most spinal cord-injured patients who are in their wheelchairs most of the day would develop sacral ulcers. In fact, that is rarely the case.

I am not saying that patients should be sitting up in chairs all day or without chair cushions-that could result in pressure ulcers over the ischial tuberosities. Instead, I am emphasizing that appropriate use of chairs is the most effective, low-risk, and inexpensive means of pressure ulcer prevention. It is important for us to remember that when helping our patients into a chair, we need to ensure that they are in a 90-degree upright position. Lying in a reclining chair or having a patient slide down in a chair puts pressure on the sacrum and can lead to pressure ulcers.

In a time when health care facilities increasingly have limited resources, it is hard to argue that we do not have enough chairs. In my opinion, the old adage of "keep it simple" certainly applies to pressure ulcer prevention.

Think chair!

Kenneth Olshansky, MD

Clinical Professor, Division of Plastic Surgery

Medical College of Virginia

Virginia Commonwealth University