April 2025: Practical Pointers for Product Development and Medical Affairs

Authors: Gerald L. Klein, MD; Roger E. Morgan, MD; Shabnam Vaezzadeh, MD; Michael Fath, PhD; Niti Goel, MD; Freddy Byrth; Emilia Jones Amaowei, MD

Clinical Development and Operations

●    Logistics is of increased importance when conducting complicated cell and gene therapy, immunotherapies, or oncology clinical trials. The therapies mentioned above often require complex cold-chain management, strict vein-to-vein time windows (the total time when cells are collected from the patient’s vein to when the engineered cells are infused back into the patient’s vein, typically within 2-4 weeks), real-time biomarker monitoring, and specialized personnel or equipment. Logistical inefficiencies can compromise the viability of autologous cell products or delay dose administration, negatively affecting both safety and efficacy outcomes.[1] Poor logistics may lead to missed dosing or testing, resulting in frustration not only among participants but also at clinical sites. Over time, these challenges can contribute to reduced study retention, strained site relationships, and compromised data quality.

●    Participant concierge transportation may foster enrollment and retention, especially in rare diseases. In both rare disease trials and studies of longer duration and greater complexity, patient  populations are often geographically dispersed and may have limited mobility due to complex health needs. Providing travel support–such as concierge services, lodging assistance, and reimbursement–can significantly improve both recruitment and adherence[2] to study protocols. This is especially critical in decentralized trial models, where on-site visits are minimized but not entirely eliminated. In such cases, the integration of remote patient monitoring systems can help address logistical challenges and maintain study engagement. It may also be useful for protocol planners and writers to adopt a multifaceted approach, rather than thinking in terms of “this and that” (e.g., either travel support or remote monitoring). Instead, a “this and that” strategy–combining travel support with decentralized solutions–may better support participants’ needs and improve trial outcomes. Importantly, these strategies are not limited to rare disease trials; they can also enhance the success of studies with longer durations or complex treatment regimens by reducing participant burden and supporting higher retention rates.

●    Vast differences may exist between effectiveness of a treatment vs its efficacy. While efficacy studies have their own merit, primarily serving regulatory approval processes, effectiveness studies play an important role. Efficacy is measured under ideal, controlled conditions (e.g., randomized controlled trials), whereas effectiveness evaluates real-world performance. The general patient population is often excluded from efficacy studies due to strict inclusion and exclusion criteria, making it challenging to extrapolate their results[3] to everyday clinical practice. As a result, vast differences may exist between a treatment’s efficacy and its real-world effectiveness. Many interventions demonstrate high efficacy but fall short in effectiveness due to factors such as patient heterogeneity, variability in adherence, and system barriers within actual healthcare settings. Real-world studies that demonstrate therapeutic effectiveness can strengthen clinical decision-making, support reimbursement efforts, and lead to more efficient and patient-centered product development.   

● Expensive protein manufacturing can be improved with the use of AI. AI models are increasingly used to optimize codon selection, expression vectors, and fermentation parameters, substantially improving yield and purity in protein biologics. Various startups use generative biology platforms to engineer custom proteins as well as closed-loop optimization.

Medical Affairs

●    Marketing and commercial key points should be planned from Phase 1 clinical trials. Early involvement of commercial and medical affairs teams in developing the Clinical Development Plan (CDP) can help shape value propositions,[4]health economics outcomes, and Key Opinion Leader (KOL) engagement strategies. Defining market access, pricing sensitivities, and differentiation points during Phase 2 and then Phase 3 studies supports faster launch readiness and payer negotiation. Collaboration with regulatory affairs at this stage also helps to ensure alignment with clinical endpoints to anticipated label claims and global submission requirements. Establishing a medical communication plan early-particularly for congresses and other medical meetings-can be highly beneficial, as data or case histories from early studies may provide valuable content for effective medical communications, including white papers, slide decks, and journal articles. In addition, early planning for real-world evidence generation and post marketing commitments can further strengthen the product's long-term positioning and support its value story across diverse markets. 

●    AI can help speed up medical communication. AI is transforming medical communication by rapidly generating and summarizing scientific publications, MSL briefings, and standard medical responses with greater consistency and compliance.[5] Natural Language Processing (NLP)-powered tools enable real-time resolution of HCP and field queries through intelligent chatbots and enhanced search capabilities. Machine learning analyzes field insights and literature to identify educational gaps, monitor sentiment shifts, and inform medical strategy. AI also supports internal alignment by generating cross-functional updates and assisting with compliant medical writing. Finally, it personalizes communication through auto-generated slide decks and regionally adapted messaging tailored to stakeholder needs. 

●    Establishing common goals with patient advocacy groups. Collaborating with advocacy groups helps to ensure that clinical endpoints, communication, and access strategies reflect patient-centered priorities. Such partnerships can also aid communication, awareness, and recruitment efforts. They enhance trial design, build trust with key stakeholders,[6] and foster co-created education content-contributions that are particularly vital in complex therapeutic areas such as oncology, immunology, neurology, and rare diseases.

Footnotes:

[1] Abou-El-Enein M, Hey SP, Leferman L. "The critical role of logistics in the success of cell and gene therapies." Nature Biotechnology. 2021;39(9):1057–1059.

[2] Esmail LC et al. "Improving patient access and engagement in clinical trials through concierge services." Therapeutic Innovation & Regulatory Science. 2022;56(4):556-562.

[3] Gartlehner G et al. "What is the difference between efficacy and effectiveness?" Agency for Healthcare Research and Quality (AHRQ). 2006.

[4] Le Meur N, et al. "Bridging clinical development and commercial strategy: The evolving role of medical affairs." Pharmaceutical Medicine. 2021;35(5):287–296.

[5] Zhang Y et al. "Using NLP for automated generation of medical communications." Journal of Medical Systems. 2021;45:92.

[6] Wicks P et al. "Patient advocacy groups: Partners in health research and drug development." Health Affairs. 2018;37(3):475-480.

References:

1.       Abou-El-Enein M, Hey SP, Leferman L. "The critical role of logistics in the success of cell and gene therapies." Nature Biotechnology. 2021;39(9):1057–1059. 

2.       Anderson M et al. "Engaging patients in rare disease research through advocacy partnerships." Orphanet Journal of Rare Diseases. 2020;15:156. 

3.       Brolund A et al. "Chatbots and AI in medical affairs: potential and pitfalls." Frontiers in Pharmacology. 2023;14:1230874.

4.       Daly B, Brawley OW, Gospodarowicz MK, et al. Remote Monitoring and Data Collection for Decentralized Clinical Trials. JAMA Netw Open. 2024;7(4).

5.       Esmail LC et al. "Improving patient access and engagement in clinical trials through concierge services." Therapeutic Innovation & Regulatory Science. 2022;56(4):556-562.

6.       Getz KA. "Patient recruitment and retention in rare disease trials." Applied Clinical Trials. 2020. 

7.       Gartlehner G et al. "What is the difference between efficacy and effectiveness?" Agency for Healthcare Research and Quality (AHRQ). 2006. 

8.       Le Meur N, et al. "Bridging clinical development and commercial strategy: The evolving role of medical affairs." Pharmaceutical Medicine. 2021;35(5):287–296.

9.       Makady A et al. "What is real-world data? A review of definitions based on literature and stakeholder interviews." Value in Health. 2017;20(7):858-865.

10.    Marks P. "The future of cell and gene therapies: logistics and regulatory convergence." FDA CBER Keynote Address. 2023. 

11.    Wicks P et al. "Patient advocacy groups: Partners in health research and drug development." Health Affairs. 2018;37(3):475-480.

12.    Zhang Y et al. "Using NLP for automated generation of medical communications." Journal of Medical Systems. 2021;45:92.