Biomedical Engineering Reference
In-Depth Information
every country usually now require objective clinical evidence obtained from a
multicenter clinical trial demonstrating the clinical effectiveness of the product
compared to the standard of care.
In the design of the protocol and clinical trial it is important to delineate the
objectives of the clinical trial, the primary and secondary outcomes of the clinical
trial, the population the product is intended to treat, inclusion, exclusion criteria,
surgical technique and outcome measurements. A robust statistical plan must also be
prepared. The statistical plan will determine the number of subjects needed to
provide statistical evidence to support the primary outcome of the study.
The study design must be established. Regulatory agencies usually request data
obtained from a randomized, controlled, blinded evaluation, multicenter clinical
trial. While this design is ideal, it may not always be feasible for trials evaluating
biomaterials for the treatment of skin loss, especially resulting from thermal
injuries. There is also a design that can be used, which is each person serves as their
own control. The advantage of this design is that usually, except in areas of minor
skin loss or single wound sites, the patient has more than one area to be treated.
This design eliminates any bias associated with randominization especially with
regard to age, gender, diagnosis or concomitant medical condition. The same
person has the investigational and control (standard of care) product used on
different sites of skin loss. The investigational product can be directly evaluated
compared to a control site in the same patient. The disadvantage is it may be
difficult to find patients with two sites suitable for treatment. If one site
(investigational or control) heals with significant better results, this may be an
issue medically and psychologically for the patient.
Blinding can be an issue in controlled clinical trials of biomaterials for skin loss,
as the products, while they are on the patient, can be noticeably different to the
clinician and patient. Blind evaluations of range of motion, healing, cosmetic and
functional attributes can be evaluated by a clinician who is blind to the treatment
when the products have been removed/incorporated into the patient's skin. Clini-
cal outcomes for evaluation of products for skin loss include time of healing, range
of motion, scarring and long term follow-up evaluations of healing, functions and
cosmetic evaluations.
Clinical trial design for chronic cutaneous ulcers and burn wounds
The FDA has published a guidance document
Chronic Cutaneous Ulcer and Burn
Wounds - Developing Products for Treatment.
34
The guidance addresses impor-
tant considerations in clinical study design regarding venous stasis ulcers, diabetic
foot ulcers, pressure ulcers and burn wounds.
In the initial phase of a clinical trial design, it is important to establish the
'indication for use' for the product. The product's labeled indication for use is
based on substantial evidence obtained in preclinical and clinical trials and safety
and efficacy data obtained from the results of the clinical trial.
