Innovations in Technology & Clinical Testing

Innovations in Technology & Clinical Testing

With our advancing understanding of the biology of fine lines and wrinkles comes the application of more sophisticated technologies and more rigorous research methods to measure the effects of topical treatments. Gone are the days of trial and error, when the efficacy of topical interventions was determined by treating symptoms without a clear sense of the underlying biological mechanisms. Now, researchers are utilizing a host of complex sciences and technologies to understand these mechanisms, and designing their studies to eliminate the uncertainties and subjectivity that colored earlier conclusions.  

Advances in Molecular Testing

At the molecular level, P&G Beauty researchers are bringing to bear several complex sciences to gain a more complete picture of skin aging. These sciences include:  

• Genomics: a branch of biotechnology which applies genetic and molecular biology techniques to the genetic mapping and DNA sequencing of sets of genes or the complete genomes of selected organisms.

• Proteomics: a branch of biotechnology which applies the techniques of molecular biology, bio chemistry and genetics to analyzing the structure, function and interactions of the proteins produced by the genes of a particular cell, tissue or organism.

• Metabolomics: the systematic study of the unique chemical finger prints that specific cellular processes leave behind; specifically, the study of their small-molecule metabolite profile.

• Bioinformatics: the use of techniques including applied mathematics, informatics, statistics, computer science, artificial intelligence, chemistry and biochemistry to solve biological problems, usually `on the molecular level.

Of these applied disciplines, one of the most exciting areas of P&G Beauty research is genomics, where the sequencing of the human genome has given scientists an exponentially larger toolbox from which to learn and innovate targeted interventions. Owing directly to the breakthroughs of modern genetics, researchers now have the ability to identify the specific human genes that are modulated in response to various stimuli.  

Gene Chip Technology

One new technology that has been developed as an outgrowth of the sequencing of the human genome is a gene-monitoring device known as the gene chip. The gene chip's versatile technology has led to it being used by researchers studying various diseases including autism, bipolar disease, cancer, diabetes and heart disease. In addition to these applications, the gene chip technology is enabling P&G Beauty researchers to understand the underlying biological basis of changes seen on the skin surface, including changes in fine lines and wrinkles.

Tiled onto an Affymetrix gene chip are oligonucleatide probes representing over 35,000 genes, This technology has revolutionized genomics research and is being used extensively by P&G Beauty scientists.

The chip itself has indicators that represent genes comprising the human genome. By placing fragments of fluorescently-tagged samples isolated from the skin onto the chip, scientists can see which genes are expressed within the sample and whether these genes are up-regulated or down-regulated, indicating specific molecular events contributing to a given biological process.

Advances in Preclinical & Clinical Testing

Along the long road from molecular to preclinical and finally clinical testing at P&G Beauty, ingredients and their subsequent product applications must pass clear safety and efficacy benchmarks before even being considered for market introduction. Beginning with testing on in vitro skin equivalents and advancing to in vivo efficacy testing, these measurements have elevated the legitimacy of skin care science and the rigor upon which skin care claims are made.  

In vitro Human Skin Equivalents

The imperative for skin product safety, combined with ethical, social and political pressures, has fostered improvements in alternatives for animal testing. One of the leading technologies that has been developed is human skin equivalent culture models. In recent years, advancements in techniques have led to cultures that mimic not only the epidermal layer but also the dermal layer, allowing these models to be used not only for safety assessments22 but also to test product efficacy.23, 24, 25

 
In vitro human skin equivalents reproduce many cellular and structural elements of natural skin, including the dermis, epidermis and melanocytes.

Human skin equivalent cultures receive nutrients from the bottom of the culture. This facilitates application of topical ingredients, both water soluble and non-water soluble, on the top of the culture. 

Today's human skin equivalents offer multiple advantages over traditional monolayer cultures:  

• Can be used to test undiluted materials (e.g., product formulations) which is important because not all materials are water-soluble

• Are able to show cell-to-cell interaction between dermis and epidermis

• Clinically relevant measures can be performed (e.g., barrier effects with TEWL, hydration)

Clinical Test Design 

In today's era of sophisticated skin science, clinicians and consumers alike are calling for data on cosmetic products that are based on the same level of scientific rigor that is required of drug trials. While such trials are voluntary and require significant investments in time and resources, P&G Beauty has long adhered to testing methodologies for cosmetic products that exceed those required by governmental regulatory bodies and that are relied upon by most beauty companies.

Consistent with this commitment, P&G Beauty regularly conducts randomized, double-blinded clinical trials. 26, 27, 28, 29, 30  Using these protocols, participants are randomly assigned to one of two or more treatment regimens, and neither the study participants nor the researchers know which participants are receiving the test therapy and which are receiving a placebo or control therapy. These measures, though exhaustive, ensure potential selection biases are eliminated and that findings are both objective and reproducible.  

Ghosting Method: Increases Accuracy of Before & After Comparisons

The technical difficulties involved with capturing visual data and the absence of clear digital image capture standards have resulted in many dubious before and after comparisons throughout dermatological literature. Facial expression, head position and lighting are all critical factors in determining whether a wrinkle has become smaller, larger or remained the same size and depth. The challenge is compounded because the more subtle the change, the more critical changes in these factors become.  

Given these challenges, it has taken advances in technology and scrupulous scientists to bring rigor to the process of effective digital imaging of aging skin. One advance that has helped solidify digital imaging as a serious documentation and measurement tool is "ghosting" technology. By replicating the original lighting and facial positioning to the most precise degree, the ghosting method helps ensure the most accurate possible assessments of skin changes, whether those changes are being determined objectively by computer image analysis or subjectively by graders or consumers.

Ghost image from baseline visit 

Aligning the ghost and current live image.

How It Works: During the subject's initial visit, the operator captures the baseline image. At follow-up, the operator recalls the subject's baseline image, or repositioning image, in a semi-transparent "ghost image" format. When the camera system is activated, it brings up both the baseline ghost image and an overlaid live subject image. The operator aligns the baseline ghost image and overlaid live image, matching the subject's live head position and facial expression with the baseline ghost image. The goal of this technological process is to minimize possible confounding variables. Not only does this help advance science by providing more precise measures, it bolsters the validity of claims and is in the best interest of consumers.

Perfectly repositioned subject, even months later

FOITS Topography Maps

In the world of skin science, the value of obtaining skin surface topography in vivo cannot be understated, but the data obtained is only as valuable as it is precise. In their ongoing quest for more precise measurement instruments, P&G Beauty researchers acquired a new measurement technology known as FOITS (Fast Optical In Vivo Topometry of Human Skin) to augment their existing topographical measurement system.

Example of POITS before and after comparison images showing the benefits of a test topical anti-aging cream. The outer boxes contain images of wrinkles in the crow's feet area following treatment with a test topical anti-aging cream. The inner boxes represent topographical heat maps of this same area and clearly indicate reduced fine lines and wrinkles. 

How It Works: FOITS uses the principle of "fringe projection" to analyze the topographic features (height variations) of the skin surface. An appropriate analogy for "fringe protection" in image capture can be made by imagining light passing through window blinds and onto an object. While stripes of light are cast onto the object, they distort the geometry of the object. But the original geometry of the object can be captured by comparing the coordinates where the light stripes meet the parallel shadow stripes. FOITS applies this same principle to skin's topographical features. A parallel stripe pattern is first projected onto the skin surface. The instrument then calculates the x-y-z coordinates where the original stripe pattern and the parallel dark pattern meet, generating precise data on the true skin topography. Upon acquiring FOITS, P&G Beauty researchers used the technology to assess the performance of existing product lines. Their findings were extremely satisfying--the technology itself yielded better measurements and the tested products met or exceeded study endpoints. This is especially rewarding, given that the FOITS system is increasingly gaining recognition for its ability to validate product claims and that the technology has been adopted as the standard for anti-aging product claims in Germany.

The Fundamentals of Preventing & Reversing the Signs of Aging Skin

• Wrinkles and poor texture are among the earliest signs of aging. Over time, the skin becomes thinner, drier and less elastic. The timing and severity of the appearance of fine lines and wrinkles is due to:
• Your genetic predisposition to wrinkles and the natural aging process 
• Exposure to sunlight and other environmental irritants, including pollution
• Overexposure to the sun is the main culprit of premature age-related changes, including wrinkles, roughness, altered pigmentation, loss of skin tone and dilated blood vessels. To protect your skin, use a daily moisturizer with broad spectrum SPF 15 sunscreen included. If you plan to be outside, apply and reapply sunscreen and don't forget to wear a hat, protective clothing and sunglasses. Try to limit your exposure to the sun during the middle of the day when UV light is at its strongest.
• Supplement the protective effects of broad spectrum SPF 15 coverage with anti-aging treatments that can help strengthen the skin, including the skin barrier, and reverse the signs of aging. These include topical antioxidants, niacinamide, N-acetyl glucosamine (NAG) and peptides, among others.
• Quit smoking or don't start. Cigarette smoke causes marked decreases in the antioxidant capacity of skin and production of new collagen.
• Exercise regularly to help flush impurities out of your skin. Exercising also facilitates the production of sebum, which is the skin's natural moisturizer, and improves blood flow to the skin.
• Optimize your immune function and skin's natural self-repair mechanisms by drinking plenty of water, eating a well-balanced diet and getting plenty of rest.

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