5.3 Clinical Strategy

Chapter 5.3
Additional Resources

As described in Chapter 5.3, there are many important considerations to take into account when developing a clinical strategy, including essential linkages to R&D, regulatory, reimbursement, marketing, and sales activities.   The steps below have been excerpted from the chapter and are presented with active web links to assist innovators in getting started.

Determine the Purpose of the Clinical Strategy

  1. What to Cover – Define specifically what end result the company hopes to accomplish through its trial strategy (e.g., Regulatory approval? Economic outcomes for reimbursement? Market data for physicians? Additional indications?). Be sure to take into account the required regulatory pathway for the device, the market, and the competitive and reimbursement landscape in which the device will be offered and the implication that this has on the study’s objective.
  2. Where to Look – Refer back to 5.2 R&D Strategy, 5.4 Regulatory Strategy, 5.6 Reimbursement Strategy, 5.7 Marketing & Stakeholder Strategy, and 5.8 Sales & Distribution Strategy.
    For information about regulatory related trials:
    • 21 CFR 812, Investigational Device Exemptions – Covers the procedures for the conduct of clinical studies with medical devices including application, responsibilities of sponsors and investigators, labeling, records, and reports.
    For reimbursement related trials:For marketing related trials:
    • MedTech Insight – Provides business information and intelligence on new trends, technologies, and companies in the medical device, diagnostics, and biotech marketplace.
    • Customer surveys and market analysis (generated in-house or by analysts in the industry).

Determine Overall Study Strategy
  1. What to Cover – Based on the technology being studied, determine the most efficient and effective trial progression to achieve the company’s goals. For example, does it make sense for the company to conduct the entire spectrum of studies, including a non-GLP animal trial, GLP acute and chronic animal trials, a first-in-man human trial, a pilot trial, and then a pivotal trial? Or, can this progression be modified to shorten the company’s time and expense, while still resulting in the necessary clinical outcomes? By creating this overall study strategy, a company will have a much better understanding of what type of study or clinical trial it needs to undertake next.
  2. Where to Look – In making this determination, the evaluation of competitive precedents is invaluable and consultation with a clinical research specialist can be very helpful.
    • Clinical Trials.gov – Provides regularly updated information about federally and privately supported clinical research in human volunteers. Note that this is not a comprehensive list of trials as registration is voluntary.
    • Competitor Websites and Other Competitive Intelligence – Competitors often provide information about their clinical trials on their websites or in other public documents (including protocol summaries). Conduct a thorough review of publicly available information.

Identify Clinical Research Specialist(s) to Work/Consult with the Internal Team
  1. What to Cover – It is common for a company to augment its own internal clinical team when preparing to design or execute a trial. In determining which clinical research specialist(s) to work with, look for experience and in-depth knowledge in the therapeutic area, experience with the type of study to be performed, and individuals/entities that can provide the company with access to a vast network of contacts and relationships in the field of study. Companies also should seek to identify individuals/entities with skills sets and expertise that complement the clinical trial experience of their in-house clinical teams.
  2. Where to Look – In addition to working with recruiters, reviewing the choices of competitors, and seeking referrals from investors, board members, and advisors, try seeking information via the following associations:

Choose a Trial Design/Model
  1. What to Cover – Based upon the company’s objectives for each study, the type of trial can be determined by considering that pilot studies (case control/retrospective or observational), pivotal studies (randomized, controlled), and post-marketing studies (registries) are used to accomplish different results. Is the strategy an incremental progression of all three types, or does one type of study support the objective? What are the regulatory implications of the trial design?
  2. Where to Look
    • BME Source: Clinical Trials – Provides a variety of resources and links related to the design of clinical trials and clinical trial strategy.
    • Center for Devices and Radiological Health (CDRH) Device Advice – Detailed guidance documents and information related to medical devices. Be sure to review the IDE Overview. Also, remember to consult with the FDA directly when an IDE is required.
    • Research Literature – Review sites such as PubMed for information about studies that have been conducted previously in the therapeutic area. Use this information to design a comparable study or to determine how to design for a competitive advantage over predecessors.

Determine Trial Endpoints
  1. What to Cover – Carefully select trial endpoints and a study design to support the trial’s objective. One or two primary endpoints should be chosen to support the most important objectives, with secondary endpoints to measure related outcomes.
  2. Where to Look
    • Research Literature – Carefully examine the medical literature for clinical studies performed in the same disease state or with a predicate device or treatment. Examine their primary and secondary endpoints and carefully evaluate if they are appropriate to support the goals of the new trial.
    • Specialty Societies – Identify the leadership of relevant specialty societies to locate “thought leaders” in the field. Thought leaders in specific disease states are critical in the determination of endpoints. Ultimately, these same leaders will evaluate the significance of results and drive device adoption.
    • Books and References on Trial Design – For example, Intuitive Biostatistics by Harvey Motulsky (Oxford University Press: New York, 1995) provides an overview of statistical principles in non-technical language and focuses on explaining the proper scientific interpretation of statistical tests rather than on the mathematical logic of the tests themselves. This book provides a non-mathematical introduction to biostatistics for medical and health science students, graduate students in the biological sciences, physicians, and researchers.

Write Research Protocol
  1. What to Cover – The study design is translated into a research protocol, which defines, in detail, all of the tactical elements of the trial, including the patient population, inclusion/exclusion criteria, the statistics (sample size and statistical power, if applicable), prior research, and prior known results.
  2. Where to Look – Reference the FDA website for guidelines about various aspects of writing a research protocol (e.g., see “Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials”). Many books and other references are also available on the topic, including:

Determine Where to Conduct the Trial(s)
  1. What to Cover – Based on the company’s objectives, determine where it makes sense to conduct the trials (e.g., U.S. versus OUS, academic institution versus private research facility). Consider issues related to access, cost, regulatory hurdles, applicability of data, contracting process, and IRB history. Determine the relevant regulatory requirements (U.S. or OUS) and prepare for IDE or foreign submissions. Based on the chosen geographic markets, identify and negotiate with the appropriate clinical sites and assign responsibilities.
  2. Where to Look – Consult with the FDA on issues related to the applicability data for studies conducted OUS. Consult other companies with studies at the institutions under consideration and gather information from them about their experiences. Refer to competitors/precedents to determine what other companies have done. Review research literature for institutions that are most commonly associated with the therapeutic area. Beware of using “marquee” names as they tend to have low enrollment, although they add credibility through name recognition. Rely on community hospitals for large patient recruitment numbers.

Determine Resources Required to Implement the Protocol
  1. What to Cover – Based on the defined research approach and targeted location, identify what resources are necessary to execute the protocol. Given the scope of the defined trial strategy, determine if all required expertise exists in-house, or if a relationship with a CRO will be required. It is also important to estimate the required budget to support the plan. In general, it is best to develop estimates based on working with academic institutions, as these almost always cost more than private research facilities. Expect the study to take about twice as long as planned, and at least double the initially anticipated cost.
  2. Where to Look – Consult other members of the company’s network, consultants, board members, and other contacts to evaluate “best practices” from other similar organizations. Use these as benchmarks in better defining the approach, timeline, and cost of the strategy. There are innumerable CROs that can also provide information⎯focus on those in the therapeutic area in which the company is focused.

Understand and Implement GCP
  1. What to Cover – At the appropriate time, implement GCP guidelines to direct the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials to provide assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.
  2. Where to Look – More about relevant GCP requirements can be found from the following resources:

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