Navigating the New World of Dermatology Trials

Dermatology clinical research is evolving rapidly in response to a regulatory landscape that favors clinical trials that are safer, more justifiable, and less burdensome to study participants. Putting the patient at the center of every phase of the research process—from discovery and preclinical testing to clinical trials and post-marketing studies—can help accelerate the path to successful commercialization.

In this article, we explore how a strategic patient-focused approach to planning and implementing dermatology clinical trials can help to bring new therapies to market.

Unmet needs in dermatology

Skin diseases are the fourth leading cause of health afflictions, affecting nearly 900 million people worldwide.¹ Despite advances in our understanding of the etiology, epidemiology, and pathophysiology of dermatologic conditions, much of the development progress has been in a small subset of diseases with multiple approved therapies, including skin infections, psoriasis, atopic dermatitis, acne, rosacea, melanoma, and actinic keratosis.

In recent years, there has been a dramatic increase in dermatology drug development activity for conditions such as atopic dermatitis, psoriasis, and melanoma, with hundreds of clinical trials currently underway or in the planning stages. For the majority of the more than 3,000 common and rare skin diseases, however, the need for safe and effective treatments remains largely unaddressed—but there is evidence that this trend could be changing.

For instance, the number of drugs approved for rare skin diseases has risen over the past ten years, particularly for skin-related cancers followed by genodermatoses (see Figure 1).² Research activity has also been bustling, with a variety of development programs involving innovative, targeted therapies.

Figure 1. Orphan drugs for skin conditions and skin-related cancers

Adapted from Karas L, et al. J Am Acad Dermatol. 2019;867-877.

Focusing on the patient perspective

With a patient-focused approach, a drug or device is designed to address specific patient characteristics and needs. Involving dermatology patients—and their families—in the research and development process optimizes both the likelihood of study success and the probability of market adoption. It is also necessary for meeting the expectations of regulators, providers, and payers.

In June 2020, the FDA announced the development of a series of guidance documents that address how stakeholders can collect and submit patient experience data and other relevant information from patients and caregivers as part of the product development and regulatory decision-making process.³ The series includes:

• Guidance 1: Collecting Comprehensive and Representative Input, published in June 2020, which discusses sampling methods that could be used when collecting patient input
• Guidance 2: Methods to Identify What is Important to Patients, available as a draft guidance, which explores methods for gathering information about issues that are important to patients and offers best practices for performing unbiased qualitative research
• Guidance 3: Selecting, Developing or Modifying Fit-for-Purpose Clinical Outcomes Assessment,forthcoming, which will address the development of potential study instruments
• Guidance 4: Incorporating Clinical Outcome Assessments into Endpoints for Regulatory Decision Making, forthcoming, which will discuss approaches, standards, and technologies for collecting and analyzing clinical outcome assessment data to drive regulatory decision making.

Additionally, the European Medicine Agency is working on ensuring that the patient voice is systematically incorporated throughout drug development⁴ and associated evidence generation.⁵

Providers value the patient perspective because they rely on not only published clinical trial data but also their empirical experience with individual patients to inform their thinking on therapeutic options. For payers, coverage decisions on dermatology treatments are increasingly driven by real-world evidence.

Integrating sponsor and patient priorities

Sponsors may be under the impression that there is an inherent tension between their clinical trial-related priorities and the priorities of patients. However, this is usually not the case.

For sponsors, the top priority is the generation of reliable, high-quality data to support regulatory approval. This data relies on identifying, recruiting, and retaining the right population of patients and promoting adherence to the clinical trial protocol.

Patients considering enrollment in a dermatology clinical trial are typically seeking a correct diagnosis, the opportunity to access a new treatment option, and improve their skin condition and quality of life. Patients may also be driven by the desire to contribute to the body of knowledge and provide benefit to others with the same condition in the future. Whatever their motivation, patients are more likely to remain in a study if participation does not significantly inconvenience their daily life.

By engaging in dialogue with prospective study participants and understanding what is important to them, sponsors can successfully integrate patient priorities into their study designs in even the most challenging rare and pediatric indications. This is also an opportunity for sponsors to differentiate their trials, especially in indications where there may be hundreds of trials competing for the same patient pool.

Incorporating patient feedback

Patient feedback can be invaluable for optimizing study design, recruitment and enrollment, and study implementation.

Study design. Recruiting, enrolling, and retaining the right population of patients begins with creating a patient-focused protocol. Inviting patients and their caregivers to review a draft protocol gives sponsors the chance to solicit honest feedback on whether the trial burden is acceptable and whether the proposed assessments and endpoints make sense. Patients may even point out missed opportunities or potential barriers to success that the sponsor has overlooked.

In rare dermatology conditions, where the natural history of the disease is poorly understood, and defined endpoints are lacking, patient input can be invaluable in shaping trial objectives and then creating endpoints to match those objectives.

Recruitment and enrollment. Involving prospective participants in the process of raising trial awareness and developing all patient-facing study-related documents helps sponsors ensure that their messaging is on-target, clear, and easy to understand. Patient feedback is also critical for identifying gaps in disease education that can be addressed in indication-specific or study-related websites or social media.

Study implementation. When a study is meaningful to patients and their families and manageable from a participation perspective, it is more likely to succeed. Ensuring that study participant and their caregivers understand and are on board with the commitment required is the first step. To keep patients engaged, sponsors and contract research organizations (CROs) should anticipate and proactively address any challenges associated with study participation, such as travel and lodging requirements.

Establishing alliances with patient organizations and patient advocacy groups, creating patient advisory boards, and incorporating focus groups and surveys allow for ongoing and transparent exchanges that can help facilitate these conversations. This may be especially useful in rare dermatology clinical trials where challenges with recruitment, adherence, and retention are amplified due to small, geographically dispersed populations.

Designing patient-focused protocols

An intense focus on patient safety is a powerful framework for decision-making when it comes to study design. The first set of questions sponsors should be asking is how to safely recruit, enroll, and follow-up with patients and how to ensure patients feel safe about clinical trial participation. Over the past year, in response to pandemic-related restrictions, changes in study conduct have been sweeping through the industry. Increasingly, study visits and monitoring procedures are being adapted to make it both safer and more convenient for patients to participate in clinical trials.

A patient-focused approach to protocol design can help enhance safety and study engagement while minimizing the participation burden. Key factors to consider when designing studies include:

• Consent. Is it possible to implement eConsent or remote paper consent?
• Study visits. How long should on-site visits be? Can some visits be remote? Which visits are essential for preserving study objectives and data integrity?
• Enrollment and retention. Which strategies can be implemented at the study and site level to improve recruitment and engagement? Can these strategies be executed virtually?
• Study procedures and assessments. Can certain procedures be performed off-site by a home nurse? What assessments can be completed via mobile health technology? Are there wearables or apps that can be used to further decrease the burden of participation? What procedures are necessary, and what may be skipped or at least included as an optional procedure or assessment?
• Data quality. Can source document verification (SDV) be reduced or performed remotely? Would a combination of central and remote monitoring work for the study without sacrificing data quality?

By making the patient the focus of the protocol, sponsors may benefit from increased study visibility, shorter timelines, and more efficient utilization of site staff and resources.

Implementing a successful dermatology trial

Based on our extensive clinical trial experience, we have identified three aspects of study implementation that are the cornerstones of successful studies:

1. Finding ways to accelerate start-up. Working with a CRO that has an established network of investigators and sites with experience in the indication of interest can help to reduce paperwork and streamline start-up. In addition, getting a head start on rate-limiting activities—such as document translation and licensing of patient-reported outcomes questionnaires—can help keep studies on track.
2. Ensuring rater consistency. Intra- and inter-rater consistency is critical for dermatology studies and downstream regulatory submissions. Developing and rolling out rigorous rater training, testing, and data monitoring can help ensure accuracy and consistency. Of course, requiring that the same investigator assesses the patient at every visit is ideal, but many sponsors will choose to keep the language in the protocol more forgiving to avoid frequent protocol deviations. That is why inter-rater variability may become a significant threat to data quality if not addressed proactively through the training.
3. Reducing source data verification. Minimizing SDV can help reduce duplication of work and time on site. Partnering with a CRO that has a risk-based quality management system that can analyze and review all data entered into the electronic case report form in real-time can reduce SDV while still ensuring data quality.

Conclusion

In a competitive clinical trial environment, sponsors are under pressure to optimize their clinical development strategy and planning to achieve regulatory approval as soon as possible. Partnering with a CRO that has experience in both dermatology and innovative clinical trial approaches can help sponsors differentiate their studies and facilitate recruitment. Using patient-focused study designs that prioritize safety and reduce participation burden without compromising data quality helps pave the path to market, answering the unmet needs of people with sub-optimally treated skin conditions.

Jasmina Jankicevic, MD, MS, CCRP, is the Vice President, Medical Affairs, Dermatology and Medical Aesthetics, Premier Research

References

1. 1Hay RJ, Johns NE, Williams HC, Bolliger IW, Dellavalle RP, Margolis DJ, Marks R et al. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol. 2014;134:1527–34
2. Karas L, et al. The impact of the Orphan Drug Act on Food and Drug Administration-approved therapies for rare skin diseases and skin-related cancers. J Am Acad Dermatol. 2019;81(3):867-877
3. U.S. Food and Drug Administration. FDA Patient-Focused Drug Development Guidance Series for Enhancing the Incorporation of the Patient’s Voice in Medical Product Development and Regulatory Decision Making. https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-guidance-series-enhancing-incorporation-patients-voice-medical. Last updated June 18, 2020. Accessed March 12, 2021
4. European Medicines Agency. Patients and Consumers. https://www.ema.europa.eu/en/partners-networks/patients-consumers#framework-for-interaction-section. Last updated December 22, 2014. Accessed April 5, 2021
5. European Medicines Agency. Reinforce patient relevance in evidence generation. https://www.ema.europa.eu/en/documents/presentation/presentation-ema-regulatory-science-2025-reinforce-patient-relevance-evidence-generation_en.pdf. Accessed April 5, 2021