Part 2 in a series on clinical trials in wound care
For part 1, click here.
By Michel H.E. Hermans, MD
In the first part of this series on the challenges of conducting clinical trials in wound care, I discussed factors that include patient populations and lesion prevalence. Additional criteria and conditions of the clinical trial will be further examined in this blog.
Concomitant Conditions Complicate Inclusion Criteria For Clinical Trials
Typical trauma patients are often young and have relatively few co-morbidities, but the injury itself may have several systemic effects: the primary trauma can cause a number of pathologies such as shock or sepsis and these systemic effects often have a major impact on healing per se.
In contrast, patients with ulcers, given their typical age, often have a number of concomitant diseases (i.e. hypertension, COPD). Some of these conditions are treated with medication such as systemic steroids and this, again, has the potential of negatively influencing healing (often the primary outcome of a trial).
Therefore, exclusion criteria often comprise of a number of these conditions: for ulcers these may be treatment with steroids and for burns the total body surface area of the burn may have to be below a certain percentage. The criteria may lead to a relatively large number of patients with the right type of lesion still being excluded from the trial.
The Effects of Adjunct Therapy on Trial Outcomes
Particularly in chronic lesions, treating only the lesion is not enough. Offloading is crucial for diabetic foot ulcers and pressure ulcers, while the use of compression is essential in managing venous leg ulcers. Thus, in dressing trials, the results are not only the consequence of the dressing per se but also of the additional interventions taken. This has a direct effect on the outcomes: the dressing or intervention itself may work very well but if the adjunct therapy is not used properly, the outcomes may still be negative.
In the example of large burns: interventions directed at the burn disease (including a number of drugs) may have an influence on the wound and its healing trajectory, i.e., reepithelialization or graft take.
Determining What the "Outcome" of the Clinical Wound Trial Should Be
The preferred outcomes of the different types of wound care trials are different. In ulcers it is healing per se while recurrence depends more on continued offloading or compression. Reepithelialization is more important than the cosmetic aspects of the scar while the typical location of the lesion, as well as the patient’s age, do not often lead to serious scarring in the first place.
Particularly in non-life threatening, partial-thickness burns, long term results (i.e. prevention of the development of hypertrophy or keloid) is most important. The type of scar in (burn) patients depends to a certain extent on their genetic make-up. Keloid formation is very rare in Caucasians but Caucasians with very light skin have a higher chance for hypertrophy. Once a trauma wound has healed, recurrence does not occur, although Marjolin’s ulcers may occur in old scars. In chronic lesions, recurrence of the same, or a similar lesion is not uncommon.
Thus, the outcomes to be studied are, or should be different. Partial-thickness burns take a short time to heal but the development (or not) of a hypertrophic scar may be the long-term consequence and, ideally, should be part of the outcomes studied. In practice, though, it turns out to be very difficult to follow patients for a year or more. Along the same lines, healing per se of a venous leg ulcer is one thing but the study of recurrence also requires a long term follow up.
The Importance of the Institutional Review Board
Many companies, particularly small ones with little money, see an Institutional Review Board (IRB) as an expensive and major hurdle and try to initiate a trial without IRB approval. However, and rightly so, most investigators will not do a study without IRB approval. The IRB serves independent review purposes that are necessary. In addition, using an IRB approved protocol may help if litigation ever comes into play.
Also, many, if not all, journals will not publish results of a study that has not been IRB approved.
Clinical trials in wound care are difficult and significantly different from trials with pharmaceutical compounds. Diseases, patients, outcomes, and inclusion/exclusion criteria are all very specific and require highly specialized protocols.
Trials are expensive and time consuming but, in many cases necessary. Carefully planning all aspects of a wound care trial (including time and funding) is required but, unfortunately, does not always happen. This may lead to a waste of money and time and/or to trial results that are non usable for any purpose.
About the Author
Michel H.E. Hermans, MD, is an expert in wound care and related topics, trained in general surgery, trauma care and burn care in the Netherlands. He has more than 25 years of senior management experience in the wound care industry. He has conducted a large number of clinical trials relating to devices and drugs aimed at wound care and related indications and diseases. Dr. Hermans speaks internationally and has authored many published works relating to wound management.
The views and opinions expressed in this blog are solely those of the author, and do not represent the views of WoundSource, Kestrel Health Information, Inc., its affiliates, or subsidiary companies.