Applicability of Healing Trajectory in Clinical Practice

Applicability of Healing Trajectory in Clinical Practice

Outcome measures or clinical endpoints are necessary, both to evaluate efficacy of potential new treatments undergoing investigation, as well as to determine effectiveness of currently used therapies. Presently, the only outcome acceptable for new treatments for venous stasis ulcers is total ulcer healing (100% closure – FDA Wound Healing Clinical Focus Group, 2001) and not surrogate endpoints.

Wound-healing trajectories provide more information about the entire continuum of the wound-healing process (Robson et al, 2000). Statistical analyses including a t-test performed on single point data (e.g., 100% closure) may not provide accurate guidance about the total effectiveness of new wound care agents over the entire wound healing process (Hokanson et al, 1991). Polansky and van Rijswijk (1994) stated that healing time curves (wound-healing trajectories) are a ‘moving picture’ of healing that provide more detail than the ‘snapshot approach’ indicate wound healing (100% closed) at the end of the study (Robson et al, 2000; Polansky and van Rijswijk, 1994).

Hill et al. (2004) compared these three methods in a single group of venous stasis ulcer patients and concluded that although initial healing rates have some general prognostic usefulness, but their poor predictive performance precludes their use as clinical trial surrogate endpoints.

The FDA Wound Healing Clinical Focus Group has stated that partial healing is not considered an acceptable wound healing claim, because the clinical benefit of statistically significant differences in wound size has not been established (FDA Wound Healing Clinical Focus Group, 2001). One surrogate endpoint could be 50% wound closure as a measure of partial healing. The predictive value of this surrogate endpoint (diabetic foot ulcers and pressure injuries) could result in shorter clinical trials, relying on specific shifts of the wound-healing trajectories from impaired healing towards an ideal endpoint (Robson et al, 2000; Hill et al, 1999; Robson et al, 2001).

The ability to predict healing time based on initial response to treatment has important benefits:

• The patient can see evidence of improvement, promoting adherence and future care
• A stalled ulcer can be identified earlier and the cause investigated with testing (e.g., biopsy or culture) and managed to maximize healing
• Preventing acute wounds evolving to chronic wounds
• Preventing wound deterioration by initiating timely interventions (e.g., compression treatment of venous ulcers)

Quantitating intermediate degrees of healing helps to decide if treatment is effective at each visit. Enabling the patient to have realistic expectations of healing time also would lead to higher patient satisfaction, adherence and planning for vacation or returning to work.

Wound healing trajectories (percent healing versus time) provide a dynamic picture of the decrease in wound burden over the entire continuum of the healing process. Improvement in healing can be determined by shifting the curve from “impaired” healing toward “ideal” healing (Figure 1). Compared to fixed endpoints (100% closure), these trajectories provide a more complete description of treatment efficacy.

Wound repair processes depend on the interaction of many time-dependent components (Robson et al, 2001). A wound healing trajectory allows one to evaluate the outcome of healing versus time. Knowing time for healing is vital, decreased healing corelates with greater rates of infection and scarring. The wound healing trajectory integrates the many time-dependent wound healing processes are affected by systemic and local deterrents to healing.