In Australia, there are more than 450,000 people suffering from chronic wounds each year1. Chronic wounds can have a significant negative impact on the lives of patients and their families. In addition, wound management can be a significant expense for patients, carers, and health services. It is estimated that wound management costs the Australian economy more than $6 billion a year1. Evaluating new treatments through clinical trials is critical to improving wound care.
Types of wounds
Wounds can occur through injuries, such as skin tears, burns, pressure injuries, or occur post-surgically. They can also result from skin infections, or be related to underlying chronic diseases, for example diabetes or peripheral vascular disease.
An acute wound can become chronic. A chronic wound does not progress through the normal stages of wound healing, i.e., it does not heal through the body’s natural healing process. A wound is considered chronic when it takes a long time to heal, heals only partially, or recurs quickly after healing.
Wound Healing Trial Considerations and Guidelines
The FDA released its Guidance for Industry in 2006, with recommendations for the development of drugs, biological products, and devices to treat chronic cutaneous ulcer and burn wounds2. There are many challenges for conducting a wound trial; outlined below are some important points to consider for trial design.
Study population and trial setting
It is important to consider the patients and type of wounds for which the treatment is intended, as the environment can influence the efficacy of the treatment. The trial setting may be defined as general hospital, emergency room, specialised wound clinic, nursing home, or home care.
Comorbidities
The complexity of the wound environment due to a patient’s comorbidities should be considered. Diabetes, obesity, autoimmune diseases, malnutrition, cardiovascular disease, end-stage renal disease, and cancer with the need for chemotherapy or radiation are important comorbidities that impact wound healing.
Recruitment
Exclusion criteria should be carefully considered to reflect the diversity in patients' own life factors, as this can greatly impact the number of eligible patients and recruitment rate. Multiple centres for recruiting may be also considered to be able to include a sufficient number of patients within a reasonable time frame. In these instances, assessment of the wound should be standardised across trial sites.
Randomisation and Blinding
Randomisation between comparison groups allows for even distribution of known and unknown cofactors to reduce bias. It may also be possible to stratify patients by factors known to influence outcomes such as age, wound size, and comorbidities. The blinding of patients and caregivers to the allocated treatment is also recommended to reduce bias. When this is not possible, blinding of an independent outcome assessor can mitigate this somewhat.
Standard care for wound healing studies
Standard of care (SoC) may include approved dressings, treatments, and/or standard procedures such as debridement, off-loading, compression, or management of wound infection. These co-interventions should be prespecified and standardised across sites and patients, where possible. Minimising these types of confounders ensures that study outcomes and treatments can be compared appropriately.
Study Endpoints
The 2006 FDA Guidance2 highlights complete wound closure as the most objective and clinically meaningful primary endpoint for wound healing trials. This is defined as 100% skin re-epithelialisation without drainage or dressing requirements confirmed at two consecutive study visits two weeks apart. It is important to use a standard wound healing definition and assessment method in trials to enable comparisons between trials.
Wound care professionals recognise that complete healing is not always achievable when evaluating new treatments. The FDA is collaborating with the Association for the Advancement of Wound Care and the Wound Healing Society to identify clinically relevant and patient-centred outcomes to serve as alternative primary outcomes for wound healing clinical trials3.
To quantitatively assess wound healing, digital imaging can also be considered. This can allow for accurate and objective collection of wound data such as surface area, 3D volume, and maximum depth.
Clinical Trial Specialists in Australia
Datapharm Australia has experience running wound healing studies, including diabetic foot ulcers, non-healing wounds, and burns. Datapharm Australia continues to build its clinical trial network of wound care specialists in Australia. Contact us today for support in running your wound healing clinical trial or if you would like to become part of our network.
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