NIH Public Access Author Manuscript J Investig Med. Author manuscript; available in PMC 2015 June 01.

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Published in final edited form as: J Investig Med. 2014 June ; 62(5): 797–803. doi:10.231/JIM.0000000000000083.

Recommendations from the IND/IDE Taskforce of the Clinical and Translational Science Award Consortium: Developing and Implementing a Sponsor-Investigators Training Program M. E. Blair Holbein, Ph.D, B.C.A.P., Department of Clinical Sciences, Center for Translational Medicine, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9066, Phone: 214-648-5009; Fax: 214-648-8683 Jelena Petrovic Berglund, Ph.D., R.A.C., Duke Translational Medicine Institute (DTMI), Duke University School of Medicine, 2424 Erwin Rd. Suite 402, P.O. Box 17969, Durham, NC 27715, Phone: 919-668-4639; Fax: 919-668-7868

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Erin K. O'Reilly, Ph.D., R.A.C., Duke Translational Medicine Institute (DTMI), Duke University School of Medicine, 2424 Erwin Rd. Suite 402, P.O. Box 17969, Durham, NC 27715, Phone: 919-668-4635; Fax: 919-613-9913 Karen Hartman, MSN, R.N., C.H.R.C., Integrity and Compliance Office, Center for Clinical and Translational Science, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, Phone: (507) 538-5238 Lisa A. Speicher, Ph.D, The University of Pennsylvania, Perelman School of Medicine, Office of Clinical Research, 150 Anatomy-Chemistry Building, 3620 Hamilton Walk, Philadelphia, PA 19104, Phone: 215-746-7410; Fax: 215-573-9687 Joan E. Adamo, Ph.D., Biomedical Engineering Clinical & Translational Science Institute, University of Rochester Medical Center, 265 Crittenden Blvd, Rochester, NY 14642-0708, Phone: (585) 275-0742; Fax: (585) 276-1122

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Gerri O'Riordan, R.N., Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, MC 5737, Stanford, CA 94305, Phone 650 867 9419; Fax 650 724-0198 Jennifer Swanton Brown, R.N., and Spectrum, Stanford Center for Clinical and Translational Research and Education, Stanford University School of Medicine, 300 Pasteur Drive, MC 5737, Stanford, CA 94305, Phone: 650-736-1730; Fax: 650-723-8552 Kathryn G. Schuff, M.D., M.C.R. Department of Medicine/Division of Endocrinology, Oregon Clinical and Translation Research Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, Phone: 503-494-1695; Fax: 503-494-6990 M. E. Blair Holbein: [email protected]; Jelena Petrovic Berglund: [email protected]; Erin K. O'Reilly: [email protected]; Karen Hartman: mailto:[email protected]; Lisa A. Speicher:

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[email protected]; Joan E. Adamo: [email protected]; Gerri O'Riordan: [email protected]; Jennifer Swanton Brown: [email protected]; Kathryn G. Schuff: [email protected]

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Introduction The Clinical and Translational Science Award (CTSA) program was established by the NIH in 2006 to enable innovative and translational research. Improving the research infrastructure in order to accelerate the discovery and implementation of translational medical advances is a goal of the program.1 The resulting group of over 60 medical research academic health centers (AHCs) funded by the CTSA form a working consortium with specialists in diverse areas of clinical research work collaboratively to meet the stated goals of the program. As part of the CTSA consortium the Regulatory Key Function Committee was established to support the protection of human subjects and facilitate communication of shared regulatory knowledge topics and methods for improvements, with the position that regulatory support should assist investigators in meeting regulatory requirements. Within the Regulatory Knowledge Key Function Committee, the Investigational New Drug/ Investigational Device Exemption (IND/IDE) Taskforce was established to facilitate the support and oversight for clinical research involving FDA-regulated products.

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Investigator-initiated clinical research is a key component of the research continuum of translating scientific discoveries into medical therapies. Much of this research includes the use of FDA-regulated products in applications that require FDA regulatory oversight. While regulatory sponsorship of investigational drug or device research is often a function fulfilled by a pharmaceutical, biotechnology or device company, it is not uncommon for an investigator to assume this regulatory management role in addition to his or her more commonly recognized investigator responsibilities and in this circumstance they become a “sponsor-investigator”. In direct contrast to a commercial enterprise, the academic sponsorinvestigator typically has minimal support for managing the broad set of regulatory sponsor responsibilities governing IND and IDE research studies.2, 3 Regulatory oversight of an IND or IDE is a task that requires a thorough working knowledge of both sponsor and investigator responsibilities. Thus, specialized training is an essential part of assuring compliance with regulatory requirements for clinical research. It should be noted that the level of training required for sponsor-investigators is incrementally more complex and distinct from the more commonly mandated Good Clinical Practice (GCP) training for investigators. The additional responsibilities of a sponsor in FDA-regulated trials in these circumstances comprise a relatively unique situation for investigators in AHCs. Indeed, this situation typifies the significant barriers to clinical and translational research posed by the need to assure proficiency of clinical investigators in meeting associated regulatory burdens.1,4 (Zerhouni 2006, Heller 2009). Berro, et al. (2011) reviewed the CTSA experience in support of IND/IDE requiring research and surveyed the 24 CTSA institutions funded at the time.5 A subsequent more comprehensive resource survey of all 62 current CTSA institutions conducted by the CTSA Consortium Coordinating Center (C4) expanded the inventory report to include all CTSA entities.6 The Berro report included the IND/IDE Taskforce recommendation that an integral component of support for sponsor-investigators should be to provide IND/IDE training. This

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current report expands upon those recommendations to specifically address required content and approaches for implementation of sponsor-investigator training at any AHC. We also incorporate the relevant findings of the C4 survey that address these issues. Compliance Education for Regulated Research Assuring that clinical research meets FDA regulatory requirements is a part of a comprehensive research compliance program. Steinberg and Rubin 2010 have described the state of compliance training for clinical research in 10 AHCs based on interviews with compliance officers at those sites.7 Their defined scope included research ethics, study design, financial compliance, technical and operation issues, and applicable state and federal regulations. They identified significant barriers to assuring adherance to compliance training that included decentralization of training resources, lack of uniformly requiring training, wide variance in methods of training, and under-appreciation of the importance. Because of the complexity of regulatory responsibilities the difficulties confronting general compliance training identified by Steinberg and Rubin are mirrored and possibly magnified for sponsorinvestigator training.

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Drug and Device Regulations and Training Standards

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The FDA regulations mandate the need for investigators selected by a sponsor to be “qualified by training and experience as appropriate experts to investigate the drug” 8 or “qualified by training and experience to investigate the device”9 Likewise in the International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice is the statement that “The sponsor is responsible for selecting the investigator(s)/institution(s). Each investigator should be qualified by training and experience …”. 10 So, neither the CFR nor the ICH provides explicit standards for qualifications or training for investigators. Equally, neither the regulatory guidelines nor the medical literature describe the content and structure of sponsor-investigator training. Consequently, the criteria and description of the training and experience of an investigator are left to the sponsor to determine. Within the federal regulations the obligations of a sponsor11, 12 as well as those for investigators13, 14 are listed which to some extent can provide the outline as to the content of training. Even though the FDA provides some web-based regulatory training resources, as listed in the first part of Table 1, no comprehensive or directional guidance is provided to delineate content or measure sponsor-investigator training adequacy. Thus, the responsibility falls to the AHCs to provide proper training as well as adequate support to sponsor-investigators who conduct research within their institutions. The requirement for such a singularly focused training presents a relatively unique problem for AHCs. Inadequate training and support could leave the sponsor-investigator and the Academic Health Center and even the entire University vulnerable to the risks of regulatory non-compliance or inadvertently expose research subjects to unexpected risks. Equally problematic is that the lack of familiarity with the FDA-requirements and perceived difficulties may dissuade researchers from pursuing promising clinical and translational research.

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Most compliance education programs initially focused on the ethical conduct of research. The development of training that addresses the ethical conduct of clinical and translational research does not specifically address the need for regulatory training including content applicable to IND/IDE research.15Yet the need for expanded regulatory scope has become apparent with the increasing sophistication of clinical research and the attendant regulatory environment5. In the initial IND/IDE Taskforce report the need, but not the content or a recommended implementation plan, of the required training is delineated.5 As a consequence of the apparent need, the CTSA IND/IDE Taskforce created a subgroup to address sponsor-investigator training. For this report, a working group of the members of the taskforce at institutions that provide IND/IDE support met to develop the consensus recommendations for sponsor-investigator training content and implementation (Table 1).

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The taskforce reviewed IND/IDE support within the represented institutions as well as the findings of the C4 resources survey.6 Some form of assistance in the preparation and submission of regulatory documents to the FDA is offered at all 61 of the 62 surveyed CTSAs and at all of the institutions represented on the taskforce. The approaches to supporting sponsor-investigators varied widely with models ranging from minimal support, up to and including mandatory use of a central service to assure regulatory compliance. Likewise, the C4 resources survey shows that approaches to training sponsor-investigators at the participating consortium members also varied.6 Many consortium members use more than one approach to training (Table 2). Within most of the taskforce institutions the training provided is mandatory and is enforced by local Institutional Review Board (IRB) policy. The Taskforce developed consensus recommendations for content and implementation of sponsor-investigators training. The recommendations were reviewed and approved by the larger Regulatory Knowledge Committee with representation from other participating CTSA-funded institutions. Models and Methods to Support Training for Sponsor-Investigators

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The specialized regulatory training needed for sponsor-investigators requires a measure of additional expertise and focus compared to more routine compliance training. The scope will necessarily include knowledge of sponsor requirements in addition to Good Clinical Practice (GCP) investigator requirements as well as IND- and IDE-associated documentation and reporting obligations. Often, the more routine GCP training is provided through a central clinical trials office and is frequently required by the IRB. Conversely, the less commonly needed IND/IDE support is more of a niche service and may not be readily available. So, institutions looking to meet the more demanding training needs may be faced with developing new courses, coordinating across normally divergent departments, and determining the best, most efficient, and cost-effective means to deliver the training. Another point to consider is that if the training is developed as an internal resource, each AHC can customize their training towards their own processes and unique institutional needs as well as provide a long term internal resource for the life cycle of the project. Finally, the resources needed to train and support sponsor-investigators in fulfilling INDand IDE-associated obligations may be all together lacking and alternative or interinstitutional resources may be required.

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Online Materials—One model of providing sponsor-investigator training is via online modules and materials. Online module training can consist of slides with text or recorded lectures and template documents that are easily accessible. An advantage of this method is that a sponsor-investigator can complete training in a timely manner in order to be able to assume the sponsor responsibilities. Importantly, online training can provide an electronic record of training. The main drawback to this approach is the lack of an interactive discussion, and thus, specific questions may not be addressed and local expertise may not be available. A list of publicly available online training tools and templates can be found in Table 3.

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Classroom Training—This type of training can be provided either in the form of formal workshops or more frequently as informal sessions. This training is usually interactive, opening the possibility for attendees to raise questions and better understand regulations and the submissions process. A workshop or seminar can be tailored for a specific institution, department or group, with their particular needs and regulatory requirements in mind. Scheduling conflicts can be a barrier to this approach, especially if this training is the only means of education offered. Within the taskforce, informal sessions or other approaches complemented the formal workshops in order to accommodate the training needs for sponsor-investigators.

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One-on-One Training—This type of training is arguably the most effective way to provide training and education to sponsor-investigators and is offered by most of the AHCs represented on the taskforce. The C4 survey showed that 57 of the 62 CTSA institutions have taken this approach to providing training.6 It can be tailored based on specific needs and regulatory issues, and be offered at the convenience of the sponsor-investigator. “Oneon-one” interaction also presents an opportunity for the sponsor-investigator to become familiar with the resources available both inside and outside of the institution. As the study progresses, continued informal interactions with the available regulatory support staff should result in long-term compliance. This may often be complemented with in-person monitoring support. However, as was the case with classroom training, this type of interaction requires the development and support of a centralized regulatory resource with trainers qualified by experience and education and with adequate time to devote to it. Centralized resources to develop and support this individualized level of training could be a financial barrier for institutions. Training Offered by the FDA—Beside the individual institutional resources, training can be obtained by attending seminars and courses offered by the FDA either in person or online (Table 3). Some of the courses contain IND/IDE specific training. In 2009, the FDA began offering an annual 3-day “Clinical Investigator Training Course”. Both the Center for Drugs Evaluation and research (CDER) and the Center for Devices and Radiological Health (CDRH) have courses offered under CDERLearn and CDRHLearn, respectively. The FDA maintains a current list of training opportunities on their website. The benefits of this type of training mirrors those of the classroom and online trainings discussed above. The drawbacks to the FDA offerings are: 1) focus is primarily on investigator responsibilities; 2) cost and

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scheduling difficulties; and 3) difficulty in tracking and documentation of training of the sponsor-investigators by the institution.

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Other models—There are a number of commercial vendors that offer regulatory training for investigators. Most of these appear to focus on GCP training as opposed to specific sponsor-investigator training. Notably, none of the IND/IDE taskforce institutions use commercial vendors for supplying either training or training materials, perhaps due to the paucity of the specialized material as well as the high costs associated with this model of training.

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Template Documents—Most of the CTSA consortium institutions (48 of 62)6 provide template documents accompanied with appropriate instruction sheets in order to train as well as assist sponsor-investigators in preparation of various regulatory submissions (initial IND/IDE submission, annual/progress report, safety reports etc.). The use of templates ensures that all regulatory elements are being addressed and provided in a structure familiar to the FDA. Those templates can be used alone or in conjunction with the classroom or “one on one” training provided. If not offered in conjunction with classroom training, the contact information of the centralized regulatory office is of importance to ensure that the templates are well utilized by the sponsor-investigator who may be unfamiliar with appropriate regulatory language. Table 3 lists some of the templates publicly available on the respective institution's website.

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Centralized Regulatory Support Office—Recognizing the importance of regulatory compliance, various institutions have formed centralized regulatory offices with a goal of providing support and guidance to the sponsor-investigators. The mandate of each respective regulatory office is different and use of the office is not mandatory at all institutions. A few offices directly prepare or assist the sponsor-investigator in completing regulatory submissions. This model is the most resource intensive thus limiting the number of institutions using this approach. While many offices provide education, support and advice, they cannot handle the total volume of submissions. Therefore, several hybrid approaches have evolved. For example, the regulatory office can complete the first regulatory submission while providing adequate training for future ones. Subsequent submissions, including IND/IDE maintenance, can be performed with guidance and assistance of the regulatory office. Approaches to Implementation of a Training Program The barriers to assuring compliance training are magnified in the specialized instances of sponsor-investigator training and support. Determining the best approach to implementation of a program at a given institution will include establishing institutional support, assessing scope of FDA-regulated research in order to determine needs, selecting the appropriate methods, and determining how best to promote the program. Ensure Leadership Endorsement Not surprisingly, developing a successful training program for sponsor-investigators closely parallels implementing and supporting compliance programs. Namely, a sponsor-

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investigator training program requires an institutional level endorsement as well as support of the program. Within the taskforce the widespread provision and endorsement of IND/IDE support in the CTSA Consortium was attributed to the implementation of institutional CTSA programs and in some cases to the accreditation standards for the Association for the Accreditation of Human Research Protection Programs (AAHRPP) .16 An effective communications plan that underscores institutional endorsement can assure that sponsorinvestigators are aware of the training requirements and understand the necessity.Enforcement at most of the taskforce institutions is implemented through the IRB by withholding final approval pending documentation of sponsor-investigator training. Interestingly, most of the taskforce reported that the sponsor-investigators were accepting of the information and appreciative of the administrative support and advice. Assess scope of FDA-regulated research: Identify Sponsor-Investigators and Training Needs

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It stands to reason that the first step in determining the appropriate approach to providing training is evaluating the anticipated need. Identifying sponsor-investigators at an institution may itself prove to be a challenge. Since the FDA regulations permit the sponsorinvestigator to submit his or her own IND/IDE applications to the Agency without requiring official sign-off or university approval, the institution may be unaware of the submission. Thus, an AHC might not be aware of all of the investigator-initiated IND- or IDE-governed studies active at any time at the institution. However, most institutions have a system to identify and track IND/IDE studies, often relying on resources from the IRB or research compliance office. Nevertheless, an accurate count is highly dependent upon the provision of relevant information provided by the investigator at the time of IRB application. More importantly, both the sponsor-investigator and institutional leadership may not be fully aware of the additional regulatory obligations associated with IND/IDE governed investigations. The needs assessment should include not only the number of active sponsorinvestigators at the institution but also an understanding of an institution's goals for growing translational research and developing investigators in this field. If the assessed demand is low, then the model to address the need may be very different from one that an institution with many potential and active sponsor-investigator protocols would choose.

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Inventory Resources Resources that can be applied to the training should be evaluated. This inventory should include the availability of people with both the skills and expertise to provide training, the presence of a centralized compliance or regulatory office, whether or not an established compliance training program with tracking is in place, and investigator and institutional awareness of the availability and necessity for training. Analyzing the needs and resources that can be applied to the training can inform the choice of the best model and whether additional resources are required to meet that model. Provide Comprehensive Training Content The required topics needed to address the regulatory obligations and the associated regulations are detailed in Table 4. The training content should be structured to cover these regulations and any additional topics necessary for a comprehensive review of the J Investig Med. Author manuscript; available in PMC 2015 June 01.

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regulations and the requirements to assure compliance. Investigator responsibilities as described in federal regulations are part of most compliance training programs but nonetheless should be included along with training for sponsor responsibilities. Assessing Effectiveness of Training Within the taskforce there was no consensus on a method to assess the effectiveness of the training. The C4 survey did not query this aspect of IND/IDE support. In general, compliance with FDA regulations and required safety reporting was assessed during routine compliance monitoring and at continuing review by the IRB. Tailor the Training Model to Institution's Requirements and Configuration

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Many models of providing IND/IDE support exist at CTSA institutions because the need for IND/IDE support varies by institution across the CTSA consortium. One-on-one training and/or making use of online training modules may best serve institutions with a limited number of sponsor-investigator protocols. Conversely, institutions with many sponsorinvestigators may choose to offer a more structured program. Most programs have elements of both approaches. It is clear that no one model universally fits all AHCs. Institutions are best served by evaluating their in-house needs first, and then adapting the training model to the environment that exists at their site. All models for training sponsor-investigators need a comprehensive approach to address the dual regulatory responsibilities. All programs should be capable of documenting training whether by certification or other mechanisms. Compliance assurance is likewise tailored to the institutional structure, whether it is administered through the IRB, the research compliance office, or other research administration offices. Mandating training assures that all sponsor-investigators are aware of the regulatory requirements that are necessary to comply with the regulations. Recommendations and Summary

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Academic Health Centers are increasingly focused on translational research. The emphasis for growth in this area challenges both institutions and their investigators to engage in complex and sophisticated research that carries an incremental regulatory burden. Based on the necessity to meet regulatory requirements as well as the potential problems of failing to meet the requirements, it is vital to ensure all sponsor-investigators are appropriately trained to assume the dual roles as both the sponsor and investigator. The taskforce recommends institutional leadership and research compliance offices accept responsibility for assuring this training. The CTSA IND/IDE taskforce subgroup endorses the following recommendations: •

Institutions should assess scope of FDA-regulated research, perform a needs analysis,and provide resources to implement a suitable training program;



The model of training program should be tailored to each institution;



The training should specifically address the unique role of sponsor-investigators and the effectiveness of training should be evaluated regularly by methods that fit the model adopted by the institution;

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Institutional leadership should mandate sponsor-investigator training and effectively communicate the necessity and availability of training.

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The contribution of the sponsor-investigator to translational science is essential. Thus, it is crucial that they are prepared for that role. These responsibilities can be overwhelming unless proper training and support are provided. Equally important is the risk assumed by institutions where this research is conducted. By providing this training, the AHC leadership can expect their sponsor-investigators are better prepared to conduct this type of research, meet regulatory requirements, and thus lead to improved protections of human subjects, increased quality of research, and innovative and truly translational research.

Acknowledgments This work was supported by National Center For Advancing Translational Sciences (NCATS) /National Center for Research Resources (NCRR) of the National Institutes of Health (NIH)Grants No. UL1TR000451, UL1TR001117, UL1RR024128, UL1RR024150, UL1TR000135, JOAN, UL1TR000003, UL1RR UL1 024120, and UL1TR000128. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH/NCATS/NCRR.

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1. Zerhouni EA. Clinical research at a crossroads: the NIH roadmap. J Investig Med. 2006; 54(4):171– 3. 2. Code of Federal Regulations Title 21 Food and Drugs Chapter I Food and Drug Administration Department of Health and Human Services Subchapter D – Drugs for Human Use Part 312 Investigational New Drug Application. ( 21 CFR 312) (Revised as of April 1, 2013). 3. Code of Federal Regulations Title 21 Food and Drugs Chapter I Food and Drug Administration Department of Health and Human Services Subchapter H - Medical Devices Part 812 Investigational Device Exemptions. (21 CFR 812)(Revised as of April 1, 2013). 4. Heller C, de Melo-Martin I. Clinical and Translational Science Awards: can they increase the efficiency and speed of clinical and translational research? Acad Med. 2009; 84(4):424–32. [PubMed: 19318771] 5. Berro M, Burnett BK, Fromell GJ, Hartman KA, Rubinstein EP, Schuff KG, et al. Support for investigator-initiated clinical research involving investigational drugs or devices: the Clinical and Translational Science Award experience. Acad Med. 2011; 86(2):217–23. [PubMed: 21169787] 6. Adamo, Joan E.; Karen, A. Survey conducted by CTSA Consortium Coordinating Center (C4). [accessed February 4, 2014] Hartman provided domain expertise and guidance in development of the C4 IND/IDE Support survey as part of the CATCHR project. Available at: https:// www.ctsacentral.org/catchr/portfolio 7. Steinberg MJ, Rubin ER. Commentary: Compliance education and training: a need for new responses in clinical research. Acad Med. 2010 Mar; 85(3):395–7. [PubMed: 20182108] 8. Investigational New Drug. 21 CFR §312.53. Selecting investigators and monitors. 9. Investigational Device Exemption. 21 CFR §812.43(a). Selecting investigators and monitors. 10. ICH Harmonised Tripartite Guideline; Guideline for Good Clinical Practice E6(R1) Current Step 4 version dated 10 June 1996. (Section 5.6.1) 11. Investigational New Drug 21 CFR §312.50 – 59. Subpart D. Responsibilities of Sponsors and Investigators. 12. Investigational Device Exemption. 21 CFR §812.40 – 46. Subpart C Responsibilities of Sponsors. 13. Investigational New Drug 21 CFR §312.60 – 69. Subpart D. Responsibilities of Sponsors and Investigators. 14. Investigational Device Exemption 21 CFR §812.100 – 110. Subpart E Responsibilities of Investigators.

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15. Teo AR. The development of clinical research training: past history and current trends in the United States. Acad Med. 2009; 84(4):433–8. [PubMed: 19318772] 16. Association for the Accreditation of Human Research Protection Programs. [accessed February 5, 2014] AAHRPP Accreditation Standards. Available at: http://www.aahrpp.org/apply/webdocument-library/aahrpp-issues-final-revised-accreditation-standards

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Table 1

Members of the Sponsor - Investigator Training Working Group of the IND/IDE

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Taskforce* Joan E. Adamo – University of Rochester School of Medicine and Dentistry. Jelena P. Berglund – Duke University Medical Center Jennifer Swanton Brown – Stanford University Karen A. Hartman – Mayo Clinic M. E. Blair Holbein – University of Texas Southwestern Medical Center Erin K. O'Reilly – Duke University Medical Center Gerri O'Riordan – Stanford University Catherine Radovich – Michigan Institute for Clinical & Health Research Kathryn G. Schuff – Oregon Health and Science University Lisa A. Speicher – University of Pennsylvania Perelman School of Medicine *

The IND/IDE Taskforce is part of the Regulatory Knowledge Key Function Committee of the CTSA Consortium. It focuses on evaluating and supporting the needs of faculty at CTSA academic health centers who are sponsor– investigators. CTSA indicates Clinical and Translational Science Award; IND, Investigational New Drug; IDE, Investigational Device Exemption; NIH, National Institutes of Health.

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Table 2

Training methods for Sponsor-Investigators within the CTSA Consortium

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Training methods

Number of respondents (60 total)

One-on-one sessions with investigators/research teams on an as-needed basis

56

Educational materials are made available online

34

Customized education sessions available upon request for small or large groups

28

Regularly scheduled, formal lecture series, symposia, or course

22

Other

10

No training offered

2

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Table 3

Publicly Available Resources*‡

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Institution

Type of Resource

Website

Clinical Investigator Course Information

www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative/SpotlightonCPIProjects/ucm201459.htm

GCP Training Availability

www.fda.gov/scienceresearch/specialtopics/runningclinicaltrials/educationalmaterials/ucm112925.htm

International Programs Communications; Training and multimedia resources by Center

www.fda.gov/InternationalPrograms/InternationalCommunications/ucm263902.htm

Office Regulatory Affairs (ORA) on-line university

www.fda.gov/Training/ForStateLocalTribalRegulators/default.htm

Center for Drug Evaluation and Research (CDER) Learn

www.fda.gov/Training/ForHealthProfessionals/default.htm

Training Continuing Education Courses CDER (course list)

www.fda.gov/Training/CDRHLearn/ucm162015.htm

www.fda.gov/BiologicsBloodVaccines/NewsEvents/ucm232821.htm

FDA (CBER)

Center for Biologics, Evaluation and Research (CBER) OCTGT Learn (Office of Cellular, Tissue and Gene Therapies) Training Center for Devices and Radiological Health (CDRH) Learn

www.fda.gov/Training/CDRHLearn/default.htm

FDA (CDRH)

Template Documents

www.dtmi.duke.edu/for-researchers/regulatory-support/investigator-ind-ide-best-practices

Training Webinars

www.dtmi.duke.edu/for-researchers/regulatory-support/ind-ide-training-webinars

UCSF

Template Documents

http://hub.ucsf.edu/ind-development-process http://hub.ucsf.edu/ide-development-process

U Penn

Template Documents and Online Presentation

www.med.upenn.edu/ohr/ind/index.html

U Pitt

Template Documents

www.o3is.pitt.edu/

FDA

FDA (CDER)

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Duke

*

Some AHCs have templates or training on their website, but not publicly available



Sites accessed February 6, 2014.

Duke Translational Medicine Institute (Duke); University of California San Francisco (UCSF); University of Pennsylvania (U Penn); University of Pittsburgh (U Pitt)

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Table 4

Topics for Sponsor-Investigator Training

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Regulatory Obligations of a Sponsor Topics:

21 CFR (IND)

21 CFR (IDE)

Submit and maintain IND or IDE

312.23 312.50

812.20 812.40

Submit annual/progress/termination report

312.33

812.150(b)(5)

312.30 312.31

812.35 812.150(b)

312.32

812.46(b) 812.150(b)(1)

312.53(d) 312.56(a)

812.43(d) 812.46(a)

312.50 312.53 312.57 54

812.45 812.43(a)(c) 812.140(b)(1-3) 812.40 54

210 211

820

312.53(c)(4) 54

812.43(c)(5) 54

312.60

812.100 812.110(c)

Submit Amendments •

Protocol changes



Changes to investigational plan



Manufacturing changes



Other (e.g. new investigator, information etc.)

Safety Reporting •

IND Safety Reports (drugs)



Unanticipated Adverse Device Effects (devices)

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Monitoring •

The sponsor shall select monitors qualified by training and experience



The sponsor shall monitor the progress of all clinical investigations being conducted under its IND/IDE

Multi-Center Trials •

Select qualified investigators and provide them with information required to conduct the study properly (investigator brochures, safety updates etc.)



Review and evaluate safety and effectiveness data from investigators

Good Manufacturing Practice: •

Ensure appropriate current GMPs for preparation of products to humans or animals

Maintain financial disclosure records for applicable clinical trials (for future submission to a marketing application) Regulatory Obligations of an Investigator Agree to personally supervise the investigation

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Ensure IRB review and approval of the study and changes to the protocol prior to implementation

312.66

812.110(a)

Ensure investigation is conducted according to the protocol and applicable regulations

312.60

812.110(b)

Protect the rights, safety and welfare of study subjects

312.60

812.100

Obtain subject's informed consent

312.60

812.100

Maintain adequate and accurate case histories of all observations of study subjects

312.62(b)

812.140

312.66

812.150(a)(1)

FDA audits/inspections

312.58 312.68

812.145

Records retention/data management

312.57 312.62

812.140(d)

Report serious and unanticipated problems to the IRB Overlapping Sponsor/Investigator Responsibilities

J Investig Med. Author manuscript; available in PMC 2015 June 01.

Holbein et al.

Page 15

Regulatory Obligations of a Sponsor Maintain control over investigational drug/device (shipment, receipt, inventory, or other disposition)

NIH-PA Author Manuscript

Labeling of investigational new drug/device

312.57 312.59 312.61-62(a)

812.43(b) 812.140(b)(2) 812.100 812.110(c)

312.6

812.5

For Applicable Clinical Trials – Ensure compliance with Section 801 of the Food and Drug Administration Amendment Acts Register the clinical trial at clinicaltrials.gov within 21 days of enrolling the first subject •

Ensure the record is updated at least annually



As the Responsible Party for the record, ensure that records are approved and released in a timely manner



If appropriate, enter study results within 1 year of reaching the primary completion date of the study

FDAAA 801

FDAAA 801

http://www.icmje.org

http://www.icmje.org

To protect publication rights – Ensure compliance with ICMJE policy regarding trials registration

NIH-PA Author Manuscript



Register the clinical trial at clinicaltrials.gov prior to enrolling the first subject



Ensure the record is updated at least every six months



As the Responsible Party for the record, ensure that records are approved and released in a timely manner

NIH-PA Author Manuscript J Investig Med. Author manuscript; available in PMC 2015 June 01.

Investigational Device Exemption Task Force of the clInical and Translational Science Award Consortium: developing and implementing a sponsor-investigators training program.

The objective of this study was to provide recommendations for provision of training for sponsor and investigators at Academic Health Centers...
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