The AI Revolution in Pharma: Remaking Medical Affairs, One Insight at a Time

MedSurgPI, LLC is pleased to introduce the AI Revolution in Pharma: Remaking Medical Affairs, One Insight at a Time.  This document highlights the role of AI, not just as an automation tool but as a game-changer for medical affairs and stakeholder engagement.  Join us as we explore the evolving landscape of AI, promising a new era of innovation and strategic partnership.

By Michael Fath, PhD1,2; Gerald L. Klein, MD2; L. Allen Kindman, MD2; Larry Florin, MBA2; Victoria Manax, MD2; Shabnam Vaezzadeh, MD2

1Cavabio Consulting, LLC, 2MedSurgPI, LLC


Practical Pointers

Practical Pointers: Product Development and Medical Affairs

Written by: Gerald L. Klein, MD; Burak Pakkal, MD, Roger E. Morgan, MD; Renu Jain, PhD; Shabnam Vaezzadeh, MD; Pavle Vukojevic, MD; Larry Florin, MBA; Victoria Manax, MD

Product Development

  1. Data Monitoring Committees in Clinical Trials: The new FDA Guidance on “Use of Data Monitoring Committees in Clinical Trials” (DMC) just came out in February 2024. [1] The FDA strongly recommends using a DMC if there is a risk of a serious mortality or morbidity due to the participant’s medical condition or if the investigation may cause serious unexpected adverse events during the trial. The agency further states that the use of such a committee is practical.

    MedSurgPI suggests that when the study is short in duration, a Safety Review Committee, (SRC) may be a more practical approach to further ensure safety of the clinical trial. This consists of a medical monitor, the principal investigator, and another medical safety expert.

  2. Overview of Device Regulation: The FDA has just issued the “Quality Management System Regulation (QMSR) Final Rule”, which amends the good manufacturing practices requirements of the Quality System Regulation (21 CFR Part 820).[2]

    Medical device manufacturers of US medical devices must adhere to the following:

    US FDA Registration Guidance | US Medical Device Registration

    Device Registration and Listing

    Premarket Notification 510(k) unless exempt, or Premarket Approval (PMA)

    Investigational Device Exemption (IDE) for clinical studies

    Quality System (QS) regulation

    Labeling Requirements

    Medical Device Reporting (MDR)

  3. Still a Need to Improve More Diverse Populations in Clinical Trials: Clinical Trials need to involve more diverse populations such as racial and ethnic minorities, the elderly, rural populations, women, etc.[3] The FDA has published a new guidance document that explains how this data is to be collected during a clinical trial: “Collection of Race and Ethnicity Data in Clinical Trials, and Clinical Studies for FDA-Regulated Medical Products: Draft Guidance for Industry.”[4] One resource, with tools and other information to help improve this situation, may be found at the National Institute of Minority Health and Health Disparities website.

Medical Affairs

  1. Keeping Current: Presenting yourself as an expert goes beyond just understanding your product; it’s crucial to be deeply knowledgeable about the conditions it treats. This requires a commitment to continuously monitoring and analyzing relevant medical literature, including newsletters, attending conferences, and reviewing clinical trial data. Keeping abreast of advancements in the field ensures that you remain a comprehensive resource for both your product and its application. This ensures that your team can provide accurate and up-to-date information, establishing yourself as a reliable source.

  2. AI Chatbots for Medical Education: Some medical information tasks can be automated by the use of AI chatbots for providing such information to health professionals and patients about medication and device indications, adverse effects, dosages, and drug interactions.

  3. Medical Affairs Microgrants: Our experience suggests that a ‘microgrant’ program can be a useful tool in obtaining greater healthcare professional (HCP) engagement. This entails establishing a very modest grant program that allows HCPs who do not conduct formal clinical trials to defray the cost of such activities as creating an article (case history), small study (observational, history, etc.) of interest to your company.

[1] https://www.fda.gov/media/176107/download.

[2] https:www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/overview-device-regulation#reg.

[3] Kim J and McDaniel D.  From Words to Action: Advancing Efforts to Reduce the Racial Gap in Clinical Research. Applied Clinical Trials. Feb 7, 2024.

[4] https://www.fda.gov/regulatory-information/search-fda-guidance-documents/collection-race-and-ethnicity-data-clinical-trials-and-clinical-studies-fda-regulated-medical.

Practical Pointers Special Edition - Investment Essentials

Written by: Gerald L. Klein, MD; Roger E. Morgan, MD; Shabnam Vaezzadeh, MD; Pavle Vukojevic, MD; Burak Pakkal, MD; Michael Fath, PhD; Renu Jain, PhD; Larry Florin, MBA; Victoria Manax, MD

In light of the recent conclusion of the JP Morgan Healthcare Conference in San Francisco, a pivotal event for global investment, there’s a noticeable shift in focus among companies and investment groups. As they reassess strategies for raising capital and evaluating a wide spectrum of sectors - including biotech, tech, digital, device, pharmaceuticals, and diagnostic technologies - we find it timely and pertinent to dedicate this month’s Practical Pointers to these emerging trends, which are currently at the forefront of investor and founder discussions.

Fundamental Topics Related to the Technology and Pathway

  1. What is the medical or technological need?

  2. What is the background science?

  3. Is there rational data proving the hypothesis?

  4. What is the patent portfolio?

  5. What is the regulatory pathway?

  6. What is the clinical trial strategy/pathway?

  7. What is the expected clinical benefit?

  8. What is the reimbursement strategy?

  9. Is there an experienced product development team running the organization?

  10. What are the competitive products?

  11. What is the exit strategy?

  12. What is the market size?

  13. What are the risks of the project?

What is the Medical Need? This is one of the most quintessential questions that helps determine the value of a scientific product. The more significant the medical need the more it may lead to quicker funding, quicker regulatory review, and more investigator engagement. For example, there is a huge need for better oncology treatments, so these products are highly valued, and a tremendous amount of venture capital is being poured into many of these companies. Meanwhile, cancer prevention is what has led to a recent reduction in cancer mortality in the U.S. Another example of a critical area is the need for vast improvement in cardiovascular disease.

What is the Science? Is the technology based on plausible and good scientific work? Can the results be replicated? What is the level of expertise of the scientists who have conducted the experiments? Is the scientific hypothesis convincing?

Is there Rational Data Proving the Hypothesis? Does the data support the hypothesis? Are there other plausible explanations for the observed effect? Does this stand up to critical scientific review?

What is the Patent Portfolio? What is the status of patent filings? Have provisional patents been filed? Are patents pending? Which countries are covered? How much longer do the patents last? Are the patents adequate to provide protection vis-a-vis current and future competition? Who owns the patents? If it is a university, what are the licensing terms? It is essential to answer the following questions: Are the patents on the composition of matter; formulation/process; methods of use; and is there confirmation of freedom to operate?

What is the Regulatory Strategy? Is the technology going to be regulated by the FDA? Will it require filing an Investigational New Drug (IND) application or an Investigational Device Exemption (IDE)? What regulatory division of FDA/EMA will review this? Is there potential for special designation; orphan drug, expedited review, breakthrough? Have you had preliminary discussions with FDA/EMA regarding regulatory and clinical pathways? Will Phase I be in a healthy normal population? At what stage will you attempt to obtain proof of concept?

What is the Clinical Strategy/Pathway? What kind of clinical data will be required? Do you have information from the FDA/EMA as to their requirements? How are you planning to generate the clinical data? Are there competitive products on the market or in development that will affect your development plan?

Will you utilize a contract research organization (CRO), fractional service providers, or your own team? Do you have the medical, clinical, and scientific expertise to create a clinical strategy to plan clinical development in the most direct, economic, and efficient manner? Will you work with academic institutions, a site management organization, and/or independent investigators? What will be the duration and expense of each clinical phase? What will be the geographic scope of the clinical program?

What is the Expected Clinical Benefit? Will this product significantly modify a disease, prolong life, improve quality of life, or have fewer side effects than current therapy? Will it improve disease diagnosis? In addition, are there pharmacoeconomic benefits of the product?

What is Your Reimbursement Strategy? Is the technology a novel product or a “me too” (one that closely imitates an existing product)? Will it treat a rare disease? If there are competing products on the market, does it have significant medical or economic benefits? Will it extend life or improve quality of life? Are there reimbursement codes or do you need to lobby for them? Are you planning to generate data for Medicare reimbursement if applicable? Who will provide reimbursement pathway advice to your team?

Do You Have an Experienced Product Development Team? How many people are on your team? Do you have full-time dedicated staff? Has your team developed similar products before? Have they attained a New Drug Application (NDA), Biologics License Application (BLA), or clearance? Does your group work in other countries besides the U.S.? What types of companies and roles has your senior leadership team been involved with in terms of their experience?

What are the Competitive Products? What are the competitive products already on the market or in development? What is your competitive advantage over them? How will they affect your clinical development, commercialization, and market potential? What other products are in development and how might they affect your development and/or commercialization strategy?

What is Your Exit Strategy? Are you planning to sell the product (or company) when you have demonstrated proof of concept? Will you try and obtain product approval before an exit? Do you intend to manufacture, and commercialize the technology yourself, seek partnership, hand off, or some combination in different geographies?

What is the Market Size? Have you identified your Total Addressable Market (TAM)? What is the overall market size, and which is your addressable market? Which geographies and populations will you target? What is your order of entry strategy? Would there be opportunities for expanding the market?

What are the Risks of the Project? Have you characterized the project risks across the full range of functional areas? Have these been quantified in a risk register? Do you have mitigations for the relevant risks?

Practical Pointers for Drug Development and Medical Affairs

Written by: Gerald L. Klein, MD: Burak Pakkal, MD; Roger E. Morgan, MD; Renu Jain, PhD; Shabnam Vaezzadeh, MD; Pavle Vukojevic, MD; Larry Florin, MBA; Victoria Manax, MD

Drug Development

In 2023, the U.S. Food and Drug Administration (FDA) published numerous significant guidance documents. Below is a selection of these key publications.

  1. Numerous types of real-world data can be analyzed in non-clinical trials such as registries, electronic health records, medical claims, and data on products used in clinical practice as part of a package for FDA regulatory product approval.[1]

    • The FDA suggests the following:

      • Early engagement will allow for timely identification of challenges in the design and planning of a non-interventional study and for discussion of how such challenges might be addressed.

      • When submitting a meeting request, sponsors should include adequate information - as outlined in FDA guidance for formal meetings - for FDA to both assess the potential utility of a meeting and to identify relevant FDA subject matter experts who should address the proposed agenda items.

  2. Optimizing the dosage for oncology products now requires a strong rationale for choice of dosage which should be provided before initiating registration trial(s):

    • To support a subsequent indication and usage:

      • Especially for oncologic diseases not adequately represented in completed dose-finding trials or for new combination regimens.

      • If sufficient rationale for choice of dosage cannot be provided, additional dose-finding should be conducted.[2]

    • The FDA further states that different dosages may be needed in different disease settings or oncologic diseases based on potential differences in tumor biology patient population, treatment setting, and concurrent therapies (for combination regimens), among other factors.

      • Applicable nonclinical and clinical data should be considered to support the proposed.

    • Different dosages may be needed in different disease settings or oncologic diseases based on potential differences in tumor biology, patient population, treatment settings, and concurrent therapies (for combination regimens), among other factors.

      • Applicable nonclinical and clinical data should be considered to support the proposed.

    • For additional information, please see FDA’s Project Optimus:

  3. When developing drugs for rare indications, the FDA frequently allows the use of innovative trial designs. These should be discussed with the appropriate division very early on. This may include Bayesian methods, n-of-1 clinical studies, randomized delayed-start designs, crossover designs, and master protocol.[3] These studies require a detailed statistical analysis plan including key features of the clinical investigation design and preplanned analysis discussed with the review team before the study initiatives.

    Canadian Regulatory Pointers

    On December 4, 2023, Health Canada’s Regulatory Operations and Enforcement Branch revised the medical device establishment licence (MDEL) application form. The form is used to:

    • Apply for an MDEL

    • Apply for an MDEL after a cancellation

    • Submit changes to your existing MDEL

    • Cancel your MDEL

    • Apply for a reinstatement of your MDEL after a suspension

      For specific details, visit the following website: https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/establishment-licences/medical-devices-compliance-bulletin/updates-frm0292-instructions.html

      Medical Affairs

      Direct-to-Consumer Prescription Drug Advertisements in television and radio in new guidance document:[4]

    • First Standard: The major statement is presented in consumer-friendly language and terminology is readily understandable.

    • Second Standard: The major statement’s audio information, in terms of the volume, articulation, and pacing used, is at least as understandable as the audio information presented in the rest of the advertisement.

    • Third Standard: In advertisements in television format, the major statement is presented concurrently using both audio and text.

    • Fourth Standard: In advertisements in television format, for the text portion of the major statement, the size and style of font, the contrast with the background, and the placement on the screen allow the information to be read easily.

    • Fifth Standard: During the presentation of the major statement, the advertisement does not include audio or visual elements, alone or in combination, which are likely to interfere with comprehension of the major statement.


    1. Considerations for the use of real-world data and real-world evidence to support regulatory decision-making for drug and biological products. Guidance for Industry. August 2023.

    2. Optimizing the dosage of human prescription drugs and biological products for the treatment of oncologic diseases. Guidance for Industry January 2023.

    3. Rare Diseases: Considerations for the development of drugs and biological products. Guidance for industry. December 2023.

    4. Direct-to-consumer prescription drug advertisements: presentation of the major statement in a clear, conspicuous, and neutral manner in advertisements in television and radio format final rule Q&A. Guidance for Industry December 2023.

Practical Pointers for Drug Development and Medical Affairs / May 2023

Written by Gerald L. Klein, MD & Roger Morgan, MD

Drug Development

  • Informed consents have grown much larger, more complex, and oftentimes uses terminology that may be difficult to understand for persons with limited language skills. [1] It is imperative to make these forms shorter, simpler, and easier to understand. Studies have demonstrated poor patient comprehension of the essential elements of the informed consent process not just in the United States but globally. [2] [3] [4]

  • The definition of a laboratory adverse event is usually described in the protocol as a value that is clinically significant in the investigator’s judgment. One frequent protocol guidance for this is having a lab test reported as clinically significant if repeated. However, many results are repeated just to ensure that the results are insignificant or are due to a procedural error (hemolyzed blood). We recommend removing “repeat laboratory testing” as an indicator of a significant adverse event.

  • Removing all patient identification is important for sites to remember when they send patient hospital records or other medical records to the sponsor or CRO. In addition to name, it also includes items such as home address, telephone number and medical record number.

    Medical Affairs

  • Making the most out of poster presentations

    • Place on social media

    • Solicit comments and questions

      • Answer appropriate questions and communicate these to a wider audience

      • Broadcast current and future work in this area when applicable

    • Write up and disseminate pertinent questions and answers

    • Create a white paper and journal articles from the data

  • Commercial booths at scientific conferences

    • Verify that a promotional committee consisting of legal, medical, and regulatory (LMR) has reviewed your booth and all material in detail. This includes the following:

      • Booth location

      • All banners

      • All printed material, videos, handouts, etc.

      • Labels, headers, designs, etc. on the booth wall

      • Location of medical science liaisons (MSLs) in relation to the commercial team

    • Detailed examination of all items is critical to maintain compliance with the regulations.

  • Product feedback is an important way to learn how health care providers are actually using your product

    • Having MSLs talk directly to clinicians is a way to gather this information. In addition, you can learn why and when they are actually using the product in this manner.

    • What difficulties or drawbacks are there to the product?

    • Can the patient experience be improved, such as administering a drug at bedtime?


      [1] Schumacher A, Sikov WM, Quesenberry MI, Safran H, Khurshid H, Mitchell KM, Olszewski AJ. Informed consent in oncology clinical trials: A Brown University Oncology Research Group prospective cross-sectional pilot study. PLoS One. 2017 Feb 24;12(2): e0172957. doi:10.1371/journal

      [2] Ibid

      [3] O'Sullivan L, Sukumar P, Crowley R, et al. Readability and understandability of clinical research patient information leaflets and consent forms in Ireland and the UK: a retrospective quantitative analysis. BMJ Open 2020;10: e037994. doi:10.1136/bmjopen-2020-037994

      [4] Wen G, Liu X, Huang L, Shu J, Xu N, Chen R, et al. (2016) Readability and Content Assessment of Informed Consent Forms for Phase II-IV Clinical Trials in China. PLoS ONE 11(10): e0164251. https://doi.org/10.1371/journal.pone.0164251

       

 

Practical Pointers for Drug Development and Medical Affairs

Written by Gerald L. Klein, MD & Roger Morgan, MD

Drug Development

  • Up to 50% of subjects have poor medication adherence in clinical trials. This can be a significant factor affecting the efficacy of the results. In order to prevent this, it may be worthwhile to do a placebo screening for 2-4 weeks to determine if the potential participant will demonstrate adequate medication adherence to be enrolled in the study.1

  • The constant change of regulations, introduction of new technology and the modifications of best clinical trial practices, makes the need for continuing staff education and training essential. This type of guidance will help maintain the highest clinical practice standard for your company and may also prevent staff turnover.

  • The signing of an Informed Consent Form is not totally adequate in obtaining a potential participants informed consent for a pharmaceutical clinical trial. The process should also involve a careful, meaningful explanation of potential risks and a commitment to attend all required patient visits and procedures. These procedures should be clearly defined so that the potential subject understands their actual commitment. This is not only a regulatory requirement but an ethical, moral, and medical obligation. If potential study participants better understand the risks and their obligations it should also aid with patient retention.3

    Medical Affairs

  • A practical method to demonstrate the application of a biopharmaceutical product may be to publish a case history or series about this topic. Through these articles, health care providers are able to identify the example with their own patients and how this product may fit in with their practice.4

  • The use of n-1 clinical studies is another cost-effective manner of conducting small pilot clinical studies.5 They are especially useful in patient-centric research and to re-evaluate chronic therapies.6

  • Medical Affairs teams frequently want to work with established experts, Key Opinion Leaders (KOLs), in specific therapeutic areas.7 These teams should have an ethical synergistic plan that provides benefits for both the clinical scientist’s research and/or patient care (as well as addressing their own needs) allowing for a prudent exchange of ideas. Rather than compensating a physician only for their time, a more useful activity will help establish a better relationship. An example is a medical liaison (working for a company that sells allergy products), contacting a prominent allergist to determine what pollens seem to cause nocturnal allergy symptoms in July in San Diego.

  1. Klein GL. The case for digital pill use in clinical trials. Clin Trial Pract Open J. 2021; 1(1): 89-94

  2. Butryn, Tracy, et al. “Keys to success in clinical trials: A practical review.” International Journal of Academic Medicine 2.2 (2016): 203.

  3. Yarborough, M. Rescuing Informed Consent: How the new “Key Information” and “Reasonable Person” Provisions in the Revised U.S. Common Rule open door to long Overdue Informed Consent Disclosure Improvements and why we need to walk Through that door. Sci Eng Ethics 26, 1423-1443 (2020).

  4. Riley, David s., et al. “CARE guidelines for case reports: explanation and elaboration document.” Journal of clinical epidemiology 89 (2017) 218-235.

  5. Duan N, Kravitz RL, Schmid CH. Single-patient (n-of-1) trials: a pragmatic clinical decision methodology for patient-centered comparative effectiveness research. J Clin Epidemiol. 2013 Aug;66(8Suppl):S21-8

  6. Vohra, S., Shamseer, L., Sampson, M., Bukutu, C., Schmid, C.H., Tate, R., …& Moher, D. (2015). CONSORT extension for reporting N-of-1 trials (CENT) 2015 Statement. bmj, 350.

  7. Scher, J.U., Schett, G. Key opion leaders - a critical perspective. Nat Rev Rheumato/17, 119-124 (2021).

Potential Errors and Corrections in Early Phase Drug Development

Clinical Trials and Practice / Open Journal

by Gerald L. Klein, MD and Roger Morgan, MD

ABSTRACT: Many foreign and small companies trying to enter the United States biopharmaceutical market make avoidable errors in their early clinical phase drug development and clinical trials. They need to first understand the risks that they must endure with patent law, regulatory hurdles, the complexity and duration of the necessary clinical trials, and the large cost of drug development, which often necessitates raising substantial capital from investors. If appropriate capital for these clinical studies must be raised, then the company must be able to clearly articulate a realistic expected return on investment to these individuals. So, they must also understand the market, its exclusivity, and the competition. This must all be put together in a sleek pitch deck. Early errors frequently begin with too few, inadequate, or poorly constructed patents. These and other risks and errors may be prevented by the use of an experienced product development team. Many of these errors could be avoided if companies used more experienced drug development professionals to assist them in selecting the optimum patent strategy, regulatory plan, budget, contract research organization (CRO), clinical investigators, and etc. It is hoped that this opinion piece will help make early clinical trials more effective and save time and money.

Read Full Article

The Case for Digital Pill Use in Clinical Trials

Clinical Trials and Practice - Open Tournal (CTPOJ)

by Gerald L. Klein, MD / Published August 17, 2021

Abstract: Medication adherence in clinical trials is significantly overestimated through every phase of drug development. This can cause a reduction in statistical power, potentially resulting in incorrect conclusions regarding efficacy, safety, tolerability, and dose-response relationships, in addition to major cost overruns. Digital pill systems enable adherence measurement through an embedded ingestible sensor paired with an external receiver. An oral pharmaceutical product is over-encapsulated by a pharmaceutical-grade shell containing a biocompatible sensor. Upon exposure to gastrointestinal fluid, the shell dissolves and the sensor is activated. Medication ingestion data is transmitted via a digital signal. Clinicians and researchers use this data to track, in real time, when and if a medication was taken. These systems have demonstrated a 99.4% rate of accuracy, and have over 15-years of supporting experience and safety data. Spurred by the accelerated adoption of technology in healthcare and in everyday life, patients have become tech-savvy. They quickly adapt to these devices, and are able to use them safely and effectively. Digital pills can be implemented in most types of studies. In early-stage trials such as pharmacokinetic and pharmacodynamic studies, or dose-finding studies, accurate information on maximum-tolerated dose levels is essential and cannot be established unless study participants are highly adherent. In later-stage pivotal trials, effective medication adherence tracking can strengthen the dataset and confidence in the study results. Significant nonadherence may generate results that do not meet statistical or clinical significance for the critical endpoints, resulting in at worst, a failed trial, or at best, the need to enroll additional patients at substantial additional cost. Most clinical trials fail to achieve statistical significance, and poor medication adherence is often an important contributor. A digital pill system can ensure the quality and integrity of adherence data, increase confidence in the overall study data, and improve clinical trial efficiency.

Full article available here


The Importance of Teaching and Fostering Clinical Research in Primary Health care

Gerald L. Klein, MD and Mark A. Brown, PhD

It is important for primary health care (PHC) teaching institutions and hospitals to create an atmosphere fostering clinical investigation for all health care practitioners (HCP). This involves not just clinical trials, but observations, examinations, and investigations are a critical part of the education of any health science students. This is the basis of science. Without knowing how to apply a scientific thought process and methodology to a clinical situation, it will prevent one from reaching their optimum abilities. Continue reading…