The success of any clinical study is dependent upon a sturdy protocol; the overall quality of the study depends on this very document. This is especially true for multicenter studies which involve many investigators and clinical staff. This article will explore the perspective of an investigator at Innovaderm Research, a Contract Research Organization (CRO) specialized in a range of dermatological indications, including acne vulgaris, atopic dermatitis (AD), and psoriasis.
1. Clarity
Eligibility. The clarity of a protocol, particularly its inclusion and exclusion criteria, is one of the most significant aspects of its design. These criteria within the protocol determine which patient is eligible and which one is not. The investigator’s role is to understand and apply these criteria. It has been observed that often, the inclusion and exclusion criteria can be too lengthy and contain too many “and/or” statements, which can complicate the efficient application of the criteria. Therefore, it is crucial that these sections of the protocol are clear and concise to ensure the investigator can accurately identify eligible patients.
Perspective is everything. The interpretation of the different professionals involved in the study (ex: coordinator, CRAs, Sponsors, etc.) who will be applying the protocol will undeniably differ. By keeping this aspect in mind, the language should be direct and stripped of any ambiguities. To facilitate the investigator’s application of the protocol, the following elements should be articulated with utmost clarity: the severity of the condition under study, the perspective on the disease, the medications that are prohibited during the study, and the specific type of patient required for the study.
Navigating co-medication. Co-medication is a crucial component of protocol design, especially in dermatology clinical trials. Patients often use high-efficacy topical products (which are not classified as drugs), and these can occasionally have adverse effects on skin diseases. Therefore, the potential impact of these products must be carefully considered in the design of the trial protocol. This is evident in acne studies, for instance, where patients are observed using a variety of products on their faces. Moisturizing creams can be extremely efficacious in the treatment of AD, this type of information should be clearly stated in the protocol as to what should be done with all the products the patients are potentially using on their skin for the duration of the study.
Avoid protocol add-ons. It is known that investigators unfortunately rarely read the entire study reference manuals, to that effect, it would be recommended to include indispensable elements of the study in the protocol itself.
2. Simple, Recruitable and Safety Focused
Less is more. A protocol should be simple and recruitable. It has been observed that when a protocol contains a higher number of evaluations, their quality tends to go down, it is recommended to have 2 or 3 physical evaluations as a touchstone. The reason behind this observation is that so often, physicians devote a certain amount of time to see a patient in the context of a research and if the number of evaluations requires 2, 3 or 4 times that amount of time, they then tend to work hastily which can affect the quality of the evaluations.
Delegation of non-medical tasks. An efficient protocol structure includes proper delegation of non-medical tasks. This step will save the investigator much needed time to perform their assigned medical duties, hence streamlining the overall process.
Safety evaluations aligned with the drug safety profile. Evidently, the #1 protocol characteristic to strive for is safety. The safety of the evaluations should be in direct line with the safety profile of the drug in the protocol. A clear example of this concept can be seen in one of Innovaderm’s recent early phase study involving a systemic medication where there was no physician examination conducted during the screening visit. Changing the method of action in this case would have been considered a deviation from protocol even though the medical professional’s practice was put into question.
3. Patient-Centricity
Reasonable number of patients reported outcomes. Despite the fact that patients do have the desire to contribute to research, they ultimately want to spend as little time as possible at the clinical research unit. To mitigate these two counterpoints, it is suggested to keep the protocol to a reasonable number of questionnaires and daily evaluations. It has been observed that protocols with 10 or 15 questionnaires might present quality issues since the patients tend to quicken the daily evaluations.
Avoid non-necessary visits. It is recommended to avoid unnecessary lengthy visits and to design the protocol in such a way that procedures are done promptly at the research center.
If possible, enable access to active treatment for all patients. This last aspect can potentially have a substantial effect for the patient recruitment process if the physician can offer all patients access to active medication.
Conclusion
Keeping your protocol clear, simple, safety-oriented, and patient-focused can have a great impact on the success of your study. These elements are significant in regard to the investigator’s perspective on the trial and can go a long way with the implicated patients.
