Getting Started

Remember that a clinical strategy must be developed in close alignment with the company’s R&D, regulatory, reimbursement, marketing, and sales strategies. The following steps can be used to initiate the development of an overarching clinical strategy and to define a tactical investigation plan for a specific study.

Determine the Purpose of the Clinical Strategy

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Define specifically what end results the company hopes to accomplish through its clinical strategy (e.g., Regulatory approval? Economic outcomes for reimbursement? Market data for physicians? Additional indications?). Be sure to take into account important work streams underway within the company, such as the required regulatory pathway for the device, the market, the competitive and reimbursement landscape in which the device will be offered, and the implications of these on the study’s objective.

Where to Look

Refer 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 more information about regulatory-related trials:

• Investigational Device Exemptions, 21 CRF 812 – Covers the procedures for the conduction of clinical studies with medical devices including application, responsibilities of sponsors and investigators, labeling, records, and reports.

For more information about reimbursement-related trials:

• Centers for Medicare and Medicaid Services – Provides information about reimbursement in the public payer system.

For information about 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 the Overall Study Strategy

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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.

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

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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.

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:

• Association for Clinical Research Professionals – An international association comprising more than 20,000 individuals dedicated to clinical research and development.
• Society of Clinical Research Associates – A community for research professionals focused on providing training and continuing education, as well as establishing and maintaining an international certification program.

Choose a Trial Design/Model

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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 achieve 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?

Where to Look

• Clinical Research Resource HUB – Provides a variety of resources and links related to the design of clinical trials and clinical trial strategy.
• Device Advice – Detailed guidance documents from the Center for Devices and Radiological Health (CDRH) 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

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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.

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 nonmathematical introduction to biostatistics for medical and health science students, graduate students in the biological sciences, physicians, and researchers.

Write Research Protocol

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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.

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:

• Guidelines for Writing Research Protocols– Information on the subject developed by the National Institutes of Health Office of Human Subjects Research (available on the NIH website).
• A Collaborative Clinical Trial Protocol Writing System by Chunhua Weng, David W. McDonald, and John H. Gennari of the University of Washington, Seattle. (IOS, Press Ebook, 2004).
• Writing Clinical Research Protocols: Ethical Considerations by Evan Derenzo and Joel Moss (Elsevier Academic Press, 2005).

Decide Where to Conduct the Trial(s)

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Based on the company’s objectives, determine where it makes sense to conduct the trials (e.g., U.S. versus international, 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 international) and prepare for IDE or foreign submissions. Based on the chosen geographic markets, identify and negotiate with the appropriate clinical sites and assign responsibilities.

Where to Look

Consult with the FDA on issues related to the applicable data for studies conducted internationally. 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.

• Device Advice
• Medical Device Foreign Regulations at Export.gov – Provides up-to-date regulations in selected foreign countries.
• FDA’s Guidance for Industry Collection of Race and Ethnicity Data in Clinical Trials – Guidance on developing a standardized approach for collecting and reporting race and ethnicity information in clinical trials conducted in the U.S. and abroad for certain FDA-regulated products.

Determine Resources Required to Implement the Protocol

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Based on the defined research approach and targeted location, determine 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.

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 – reach out to those in the therapeutic area in which the company is focused.

Understand and Implement GCP

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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.

Where to Look

More about relevant GCP requirements can be found from the following resources:

• Investigational Device Exemptions 21 CFR 812 – Covers the procedures for the conduct of clinical studies with medical devices including application, responsibilities of sponsors and investigators, labeling, records, and reports.
• Protection of Human Subjects 21 CFR 50 – Provides the requirements and general elements of informed consent.
• Institutional Review Boards 21 CFR 56 – Covers the procedures and responsibilities for IRBs that approve clinical investigations protocols.
• Financial Disclosure by Clinical Investigators 21 CFR 54 – Covers the disclosure of financial compensation to clinical investigators, which is part of the FDA’s assessment of the reliability of the clinical data.
• Design Controls of the Quality System Regulation 21 CFR 820 Subpart C– Provides the requirement for procedures to control the design of the device in order to ensure that the specified design requirements are met.