PART I
Most of the clinical testing conducted for cosmetics and personal care products, either for safety or for efficacy, are interventional studies and not observational in nature. Interventional studies are designed to determine whether experimental treatments are safe and/or effective under controlled regimen and environment. Observational studies aim at analyzing specific issues in relatively large populations in a natural setting. This means that in an interventional setting, a selected population is put under specific regimen of treatment for a certain period of time and is observed and measured at pre-determined time intervals. Who are the people testing your products? What do they do in life? What are their dreams, their desires, their problems, their motivation? Why do they enroll to the study for your product? What do they know about your product? What do they know about your path to develop it? What do they know about you? And, most importantly, how can you frame and control their selection so the study objective is best served? These people are the foundation of your study. Without them and their commitment, the study cannot be performed.


When you are sending your product to be tested by a clinical research organization (CRO) or have a study director appointed to conduct it in-house, you are connecting to a population of humans through a mediator. You are influencing their life for a purpose you believe is meaningful. How do you ensure that this selected panel is the most appropriate for your product? If you neglect or underestimate the selection of a precise panel, not only can your study results become meaningless and remote from your goal, but you in fact wasted your time resources as well as the panelists’. Understanding the required population characteristics, defining it and expressing it clearly in the protocol is one of the critical aspects in study design.


Unlike in the pharmaceutical industry, for example, where the FDA sets guidelines to testing criteria for skin diseases such as acne, there are no specific detailed cosmetic and personal care guidelines for forming such criteria and they are to be customized for the study objective. Sometime, when relevant, selected criteria may be adopted from pharmaceutical guidelines. Outlining these principles should be a collaborative effort between marketing and R&D. Marketing professionals should frame the market population to which this product is created. A precise, detailed description allows more specific and accurate recruitment. Knowing the prevalence of such population in the geographical area of recruitment can further ease the process. If the prevalence is low, the criteria should be adjusted or a different facility that can recruit this population should be selected. For example, if the product is aimed at specific ethnicity and the clinical facility is located in an area at which such ethnicity is rare demographically, the recruitment of the desired panel may not be possible and a more appropriate CRO for the population should be considered. Research and development professionals should further add and refine the criteria based on clinical and scientific attributes.


Exclusion/Inclusion


The selection of an appropriate study population is a key in the overall study success. Many times the study sponsor counts on the CRO available pool of panelists, however, this population may not be ideal for the desired study and since the CRO is not aware of specific attributes of the product developed it should be carefully directed at the relevant study population to recruit.


This criteria of defining the panelists to participate in the study is termed “exclusion/ inclusion” criteria and it is aimed at shaping the study to produce reliable results. The “exclusion criteria” are those that preclude a panelist to participate in the study. For example, if the product is targeted at demonstrating an effect on mild to moderately oily skin; the study director should consider excluding panelists with very oily skin and should set a baseline criteria for such by which “mild-moderate” can be differentiated from skin that is very oily.
Generally, the inclusion criteria are composed to serve the goal of the study and the exclusion criteria to protect the panelist and/or to ensure that inappropriate population is not selected. The inclusion criteria should be broad enough to allow the CRO relatively easy recruitment and precise enough so that the relevant panelists are enrolled. It should be stressed that the population selected for the study should not be such that exhibits better odds to respond under the study conditions but rather such that reflects the population to which the product will be marketed. For example, if the product is aimed at elderly population, such population may be slower and less responsive to the treatment when compared to a younger population. Still, the age range to which the product is marketed should be reflected in the study design.


Typical “exclusion/ inclusion” criteria refer to aspects such as: age range; ethnicity; gender; skin condition; exclusion of disease that is systemic or topical; lifestyle; drug or vitamin intake; pregnancy or maternity; ability to understand treatment regimen; study goals and product’s intended use; and consent, commitment, practical, physical and mental ability to follow the treatment protocol.


A very important criterion that is often missed in the protocol is assurance that the panelists recruited are not already using a product that exhibits a similar effect to the tested product or a product that may affect the study results. Such a product can be a cosmetic, drug, topical, oral or other systemic. In fact, since a normal skin cell turnover is approximately 30 days ideally, study protocol should include a clause that panelists should not be using any skin care or other product that may interfere with the study results at least four weeks before the study begins, preferably even six weeks.


Study Design


When selecting the population for the study of interest and after the objective is clearly defined the protocol designer should ensure study is shaped to produce valid results. The validity of the study should be internal and external in nature. The purpose of internal validity is to shape the study in a manner at which the treatment applied indeed works for the defined population. For this reason, the protocol should control important variables to ensure that only the intervention of interest and no other treatment impact the outcome. For example, in a study with an objective to measure skin barrier strength by transepidermal water loss (TEWL) at which the active of interest is incorporated into an emulsion base, it is imperative that the base itself is tested as a control since it is reasonable to anticipate some effect on TEWL; as such, the results of the treatment of active can be normalized to the base as the control.


The external validity addresses results generalization. Here, the protocol should be designed in a manner that will allow concluding from study population to the general population or marketed population of interest. A product that is aimed at women in their 50-60s should be tested on peri- or post-menopausal women of this age. If such a product is tested on a younger population its results cannot be generalized to the population of interest.


Since it is very possible for one or two exclusion criteria to exhibit a dramatic effect on the study population, a close collaboration should be established with the clinical research facility to ensure that these criteria do not significantly limit the recruitment capabilities. Moreover, both the product manufacturer and the laboratory should remain flexible to modify the criteria if, when recruitment begins, the criteria limits significantly the panel recruited. Such modification could be either dropping the problematic parameter altogether if not critical for the study or, if critical, limit the duration to which the exclusion applies, reducing or modifying the limiting factor or imposing additional conditions to be met.


Exclusion criteria to consider include pregnant or breast feeding; hormone therapy; inflammatory and/or allergic skin conditions chronic or relapsing such as atopic dermatitis, rosacea, psoriasis and alike including telangiectasias (“spider veins”); adult acne; history or current skin cancer; herpes infections; history of keloids; cardiac abnormalities; diabetes; facial irradiation and/or peel; extensive aesthetic procedures; unrealistic panelist expectations; significant systemic and/or inflammatory disease; HIV; significant immunosuppression; emotional instability or mental illness; and scleroderma or collagen vascular diseases.


The inclusion criteria should be detailed to allow recruitment of desired panel. Study design may include and reference known published scales that can fully adopted or modified as needed. Examples for known scales in a skin aging study that can be adopted and/or modified for inclusion criteria may be the classification by Glogau and Fitzpatrick (see charts below).


Glogau scale was developed by the dermatologist Richard Glogau.  It was developed to objectively measure the severity of photoaging and especially wrinkles. The Fitzpatrick scale is a numerical classification scheme for human skin color. It was developed in 1975 by Thomas B. Fitzpatrick as a way to estimate the response of different types of skin to ultraviolet (UV) light.


In summary, the panelists selected for the study provide the foundation baseline for its success. They should be selected carefully and highly respected. The CRO conducting the study should be instructed as to the selection criteria and its meaning. Since it was not involved in the product design, it must be guided by R&D. 

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Nava Dayan
Owner
Dr. Nava Dayan LLC

Nava Dayan Ph.D. is the owner of Dr. Nava Dayan L.L.C, a skin science and research consultancy and serving the pharmaceutical, cosmetic, and personal care industries. She has 25 years of experience in the skin care segment, and more than 150 publication credits.
Tel: 201-206-7341
E-mail: [email protected]