- Email: [email protected]
Providing research and research training infrastructures for clinical research in the reproductive sciences
Education
Providing research and research training infrastructures for clinical research in the reproductive sciences Louis V. DePaolo, PhD, and Phyllis C. Leppert, MD, PhD Bethesda, Md The Reproductive Sciences Branch of the National Institutes of Child Health and Human Development has created pioneering new research and research training programs that address the impending shortage of physician-scientists in obstetrics, gynecology, and women’s health and the need to bolster translational and clinical research. This article provides a brief overview of the Specialized Cooperative Centers Program in Reproduction Research, the National Cooperative Program for Infertility Research, the Reproductive Medicine Network, the Reproductive Scientist Development Program, the Women’s Reproductive Health Research Career Development Program, and the Contraception and Infertility Research Loan Repayment Program and describes how these programs collectively create an infrastructure to promote the next generation of physician-scientists and to provide an information exchange between basic and clinical investigators. A key component in increasing the number of clinical investigators is the Contraception and Infertility Research Loan Repayment Program. This program has enabled clinicians to be involved in research without having to be concerned about educational loan debt. Other component programs provide basic/translational, clinical hypothesis–oriented research and clinical trials research infrastructure. The programs created are individually strong and collectively poised to support translational and clinical research efforts and to build a well-trained cadre of physician-scientists. The collective use of these types of programs is proposed as a model for the National Institutes of Health. (Am J Obstet Gynecol 2002;187:1087-90.)
Key words: Reproduction, physician-scientist, education, research training
In analyzing the current state of medical research in the United States, Rosenberg1 warned that the biggest threat to the medical research enterprise was a shortage in physician-scientists. He went on to state that this is not a new problem, but one that seems to be more glaring at this point in time, given the fact that medical research is on the brink of making great advances, particularly in genetic medicine. Although Rosenberg is correct in stating that “no single agency can meet this challenge (increasing the number of physician-scientists) alone,” it is clear that the National Institutes of Health (NIH), the lead agency in supporting biomedical research, must take a leadership role in building the cadre of clinical researchers who can bring the knowledge of the human From the Reproductive Sciences Branch, Center for Population Research, National Institute of Child Health and Human Development, National Institutes of Health. Received for publication February 8, 2002; accepted April 19, 2002. Reprint requests: Phyllis C. Leppert, MD, PhD, Chief, Reproductive Sciences Branch, Center for Population Research, National Institute of Child Health and Human Development, Building 61EB, Room 8B01, NIH, Bethesda, MD 20892; e-mail: [email protected]. 6/1/125896 doi:10.1067/mob.2002.125896
genome to bear on new diagnostics, therapeutics, and cures for human disease. Equally disconcerting to the biomedical research enterprise is the lack of sustained success of physician-scientists in securing research funding. It is no secret that clinical research grant applications fare less well in peer review than their basic science counterparts, particularly in study sections in which both basic and clinical research grants are reviewed. Indeed, individuals who are involved in the ongoing efforts to reorganize the NIH Center for Scientific Review study sections are grappling with how to provide the best review environment for clinical research applications. Tied into this conundrum is how best to transfer knowledge effectively and efficiently from the laboratory to the bedside and alternatively from the clinical environment to the bench. Couple the low success rate of grant applications submitted by clinical investigators with the declining number of physician-scientists, and one can envision easily a situation that harbingers a future with little or no translational research. The Reproductive Sciences Branch (RSB) in the Center for Population Research at the National Institute of Child Health and Human Development (NICHD) is the 1087
1088 DePaolo and Leppert
main funding unit within the NIH that provides support for biomedical research in the reproductive sciences. Cognizant then of the impending shortage of physicianscientists in obstetrics, gynecology, and woman’s health and of the need to bolster translational and clinical research, the RSB set out in the 1990s to create new research and research training programs that could address both deficiencies. These programs include the Specialized Cooperative Centers Program in Reproduction Research, the National Cooperative Program for Infertility Research, the Reproductive Medicine Network, the Reproductive Scientist Development Program, the Women’s Reproductive Health Research Career Development Centers Program, and the Contraception and Infertility Research Loan Repayment Program. This article will provide a brief overview of each program and will describe how the programs collectively seek to create an infrastructure to produce the next generation of physician-scientists and to provide a platform for information exchange between basic and clinical investigators. Specialized Cooperative Centers Program in Reproduction Research The Specialized Cooperative Centers Program in Reproduction Research (SCCPRR) was created in 1998 in response to a perceived need to increase translational research efforts in the reproductive sciences. The SCCPRR is a research-based center program that was designed to promote multidisciplinary interactions between basic and clinical scientists so that breakthroughs in our fundamental understanding of key reproductive processes are translated into clinical practice and so that questions that arise in the clinic may be addressed expeditiously in the laboratory. To ensure efficient transfer of knowledge between the clinic and laboratory, the SCCPRR is administered through a series of cooperative agreements, with each awardee institution using the U54 Specialized Cooperative Research Award mechanism. Currently, there are 14 centers in the network. The breadth of research covered by the SCCPRR is commensurate with the expansive research mission of the RSB. For a center to be funded, at least 3 research projects (including 1 project with a clinical focus) and an administrative core must be approved by the review committee. Other than those funding requirements, the investigator is given the flexibility to design a program that best suits the collective needs of the center. For example, centers may establish consortium arrangements with outside institutions that include foreign sites. Moreover, technical cores can be configured to service only the approved research projects (closed access) or to service those projects and other funded projects within the RSB mission research areas at the awardee institution (open access). In the case of a unique or expensive technology, the institu-
October 2002 Am J Obstet Gynecol
tional core is allowed to provide service to investigators at other SCCPRR centers sites. An important role for NICHD staff in coordinating research activities of the SCCPRR is to help identify and facilitate across-center collaborations and to identify potential opportunities for collaborations with outside entities, such as industry. One means to promote intercenter collaborations has been the establishment of Research Focus Groups in 4 high-emphasis reproductive science areas; endometrial function and dysfunction, ovarian physiology and pathophysiology, male reproduction, and neuroendocrine/pituitary function. Membership of these focus groups consists of a mix of basic and clinical investigators. These groups have been given the opportunity to submit collaborative research initiatives as a means of supporting collaborative efforts amongst SCCPRR centers. Thus far, these initiatives have focused on applied and clinical research in the areas of female contraceptive– lead development, endometriosis, and premature ovarian failure. A fifth focus group, resources/bioinformatics, apprises NICHD of resource/informatics needs of the SCCPRR. As a result of its recommendations, the SCCPRR supports the operation of 4 human tissue banks, 1 nonhuman primate tissue bank, a microarray core facility, and a laser capture microdissection facility. These resources are housed at various center sites in the SCCPRR network and are available to all SCCPRR investigators. Finally, the SCCPRR has supported the establishment and continues to support the maintenance of 2 online databases that deal with the ovary (http://ovary. stanford.edu/) and male reproductive genetics (http://mouse.genetics.washington .edu/). (For further information on the SCCPRR, visit http://reprobio.stanford.edu/sccprrnet/index.html.) National Cooperative Program for Infertility Research In 1991, the National Cooperative Program for Infertility Research (NCPIR) was created in response to legislative directives included in the deliberations of the 101st Congress that stressed the need to enhance support for research on the diagnostic and therapeutic aspects of human infertility alleviation. The NCPIR pioneered the use of a NIH cooperative agreement mechanism (U54) that is now used to administer the SCCPRR. Two centers, 1 at Massachusetts General Hospital and 1 at the University of Michigan, were supported between 1991 and 1996. The current NCPIR sites include Massachusetts General Hospital and the University of Pennsylvania. During the first 5-year period, projects at both center sites represented a blend of basic and clinical research. However, funded projects at the current NCPIR sites almost exclusively involve patient-oriented research with emphasis on the genetic basis of polycystic ovarian syndrome. The NCPIR also provides a stellar research environment for the training of clinical residents and fellows and for ju-
Volume 187, Number 4 Am J Obstet Gynecol
nior faculty members who were seeking additional research training. Similar to the SCCPRR, applicants for NCPIR awards can format their center structure to maximize their strengths. Reproductive Medicine Network The Reproductive Medicine Network (RMN) was established in 1990 to carry out large, multicenter clinical trials in the areas of male and female infertility and reproductive diseases and disorders. Results of these trials are expected to have immediate impact in clinical practice settings. There currently are 8 clinical sites participating in the network and 1 data coordinating center. As with the SCCPRR and NCPIR, the RMN is administered as a cooperative agreement with the U10 Cooperative Clinical Research Award mechanism. Decisions regarding topic areas to be studied, protocol design and execution, and publication of results are made by a steering committee comprised of the principal investigators of the clinical and data coordinating sites, NICHD staff, and an independent chairperson. An independent Clinical Trials Advisory Board assists the choice of topics to be studied and in priority setting. In addition, NICHD has appointed a Data and Safety Monitoring Committee to the network. Thus far, the network has completed 1 protocol that compared intrauterine versus intracervical insemination in couples in whom the female partner was apparently normal. Ongoing protocols include comparison of semen analyses from male partners of infertile couples and the usefulness of endometrial biopsy in infertility treatment, including an interobserver variability study. A clinical trial of the use of metformin versus metformin and clomiphine citrate versus clomiphine citrate in the treatment of polycystistic ovarian syndrome has been launched. Additional information can be obtained at http://rmn.deri.duke.edu. Reproductive Scientist Development Program The RSB participates in a private sector career development program for obstetrician-gynecologists, the Reproductive Scientist Development Program. Partial support for the program is from a Mentored Research Scientist Development Program Award (K12). The program independently recruits and selects its own candidates. Participants undertake a phase I research experience under a basic science mentor, with the second and third phases the initiation of an independent research program at the sponsoring institution. Women’s Reproductive Health Research Career Development Centers Program Established in 1998, the Women’s Reproductive Health Research (WRHR) centers seek to support the research career development of obstetrician-gynecologists by bridging clinical training with a career in basic, transla-
DePaolo and Leppert 1089
tional, and/or clinical research that is relevant to women’s reproductive health. The Mentored Clinical Scientist Development Program Award (K12) is used to administer this program. The award is given to academic medical institutions to enable these institutions to provide a nurturing environment for the training of physician-scientists for a career conducting research in obstetrics/gynecology and/or its subspecialties (such as maternal-fetal medicine, gynecologic oncology, reproductive endocrinology) and emerging subspecialties (such as urogynecology). The institution recruits and selects its own scholars contingent on NICHD approval. These awards provide salary support for mentors, WRHR scholars, and technical staff and funds for supplies and equipment. As with NIH K awards in general, the support of scholars through the WRHR program provides release time from other clinical and teaching responsibilities. Currently, the NICHD with cosponsorship from the NIH Office of Research on Women’s Health supports 20 centers from around the country. Contraception and Infertility Research Loan Repayment Program In 1997, the NICHD announced the availability of a loan repayment program for educational loan debt under the auspices of the NICHD Contraception and Infertility Research Loan Repayment Program (CIR-LRP). The program, authorized by Section 487B of the Public Health Service Act as amended by Public Law 105-392, provides for the repayment of educational loan debt of qualified health professionals (including graduate students) who agree to commit to a period of obligated service of not less than 2 years conducting research with respect to contraception and/or infertility. According to laws that regulate Federal LRPs, the CIR-LRP pays up to $35,000 of the principal and interest of a participant’s educational loans for each year of obligated service and will reimburse participants an amount equal to 39% of the tax liability as a result of the repayments being reported as income. The purpose of the CIR-LRP is the recruitment and retention of highly qualified health professionals who conduct contraception and/or infertility research. With its inception in 1997, the CIR-LRP became the first NIH LRP for extramural investigators. Participation in the CIR-LRP is limited to individuals who, at the time of participation, are in employment/ training at an NICHD intramural laboratory or an NICHD-supported extramural site, which includes centers that belong to the SCCPRR, NCPIR ,and WRHR programs and clinical or data coordinating units for the RMN. From 1997 through 2001, the CIR-LRP has executed 38 contracts. Thirty-one of these participants have been affiliated with either the WRHR (12 participants), SCCPRR (9 participants), or NCPIR (5 participants) centers or the RMN (5 participants).
1090 DePaolo and Leppert
Additional information regarding the CIR-LRP can be obtained at http://www.lrp.nih.gov/about/extramural/CIR/index.htm. The Infrastructure Now that we have presented a brief overview of the individual components, it is time to examine how each component and the interplay of components can create an infrastructure to enable the successful pursuit of translational and clinical research by an increased cadre of physician-scientists. One of the key components in increasing the number of clinical investigators is the CIRLRP. Faced with an enormous educational debt, many recently-trained medical doctors do not even consider a career in research. The CIR-LRP has enabled some clinicians to at least taste the fruits of the research environment without having to worry about paying their loan debt. Indeed, it is no surprise that almost 70% (26/38 participants) of CIR-LRP participants have held the MD or joint MD-PhD degrees. Hearing the LRP participants speak of being able to raise families and have mortgages because of their participation in the LRP has meant that this program has made a substantive difference in the lifestyles of these young clinicians. The training grounds for many of the LRP participants and others have been the programs that were described earlier. Most important among these are the WRHR centers. These centers give the clinician scholars-in-training their first extensive exposure to research design and methods and how to deal with patients as human subject participants in clinical studies rather than just patients. In some cases, exposure of the WRHR scholars to basic, translational, or clinical research has been in the laboratories of investigators who belonged to the SCCPRR or NCPIR because WRHR centers have been awarded to 6 institutions that are SCCPRR center sites (or consortium sites for the SCCPRR) and 2 institutions that are NCPIR center sites or, at least, affiliated with a NCPIR site, as is the case for the Harvard University system of hospitals. Fi-
October 2002 Am J Obstet Gynecol
nally, some scholars have been given the opportunity to participate in the design, conduct, and analyses of clinical trials through the RMN. Although perhaps not by design, the SCCPRR, NCPIR, and RMN represent the 3 cornerstones of the clinical research infrastructure, namely the basic/translational component (SCCPRR), the clinical hypothesis–oriented research component (NCPIR), and the clinical trials component (RMN). Because no one program can take basic research knowledge directly into the clinic, efficient translation of basic research into clinical practice requires interactivity of programs. In 1 example, a recent protocol has been approved for phase I clinical trials in the RMN on the basis of a study that was conducted by SCCPRR investigators at the University of Virginia on the use of metformin to induce ovulation in clomiphene-resistant women with polycystic ovarian syndrome. It is likely that the RMN will tap SCCPRR and NCPIR sites to help recruit patients into the clinical trial, particularly as it pertains to individuals from special or diverse populations. In yet another example, basic scientists from the SCCPRR are collaborating with clinical investigators from the NCPIR in examining the role of the fragile X mental retardation gene in the cause of premature ovarian failure. In closing, the RSB has been visionary and perhaps fortunate (ie, Congressional directives to establish the NCPIR and CIR-LRP) in its creation of programs that individually are strong and collectively are poised to support translational and clinical research efforts and to build a well-trained cadre of physician-scientists to do the research well into the 21st century. We propose that the collective use of these types of programs be used as a model by NIH staff in scientific areas in which similar deficiencies can be identified. REFERENCE
1. Rosenbert L. Physician-scientists: endangered and essential. Science 1999;283:331-2.
Providing research and research training infrastructures for clinical research in the reproductive sciences Louis V. DePaolo, PhD, and Phyllis C. Leppert, MD, PhD Bethesda, Md The Reproductive Sciences Branch of the National Institutes of Child Health and Human Development has created pioneering new research and research training programs that address the impending shortage of physician-scientists in obstetrics, gynecology, and women’s health and the need to bolster translational and clinical research. This article provides a brief overview of the Specialized Cooperative Centers Program in Reproduction Research, the National Cooperative Program for Infertility Research, the Reproductive Medicine Network, the Reproductive Scientist Development Program, the Women’s Reproductive Health Research Career Development Program, and the Contraception and Infertility Research Loan Repayment Program and describes how these programs collectively create an infrastructure to promote the next generation of physician-scientists and to provide an information exchange between basic and clinical investigators. A key component in increasing the number of clinical investigators is the Contraception and Infertility Research Loan Repayment Program. This program has enabled clinicians to be involved in research without having to be concerned about educational loan debt. Other component programs provide basic/translational, clinical hypothesis–oriented research and clinical trials research infrastructure. The programs created are individually strong and collectively poised to support translational and clinical research efforts and to build a well-trained cadre of physician-scientists. The collective use of these types of programs is proposed as a model for the National Institutes of Health. (Am J Obstet Gynecol 2002;187:1087-90.)
Key words: Reproduction, physician-scientist, education, research training
In analyzing the current state of medical research in the United States, Rosenberg1 warned that the biggest threat to the medical research enterprise was a shortage in physician-scientists. He went on to state that this is not a new problem, but one that seems to be more glaring at this point in time, given the fact that medical research is on the brink of making great advances, particularly in genetic medicine. Although Rosenberg is correct in stating that “no single agency can meet this challenge (increasing the number of physician-scientists) alone,” it is clear that the National Institutes of Health (NIH), the lead agency in supporting biomedical research, must take a leadership role in building the cadre of clinical researchers who can bring the knowledge of the human From the Reproductive Sciences Branch, Center for Population Research, National Institute of Child Health and Human Development, National Institutes of Health. Received for publication February 8, 2002; accepted April 19, 2002. Reprint requests: Phyllis C. Leppert, MD, PhD, Chief, Reproductive Sciences Branch, Center for Population Research, National Institute of Child Health and Human Development, Building 61EB, Room 8B01, NIH, Bethesda, MD 20892; e-mail: [email protected]. 6/1/125896 doi:10.1067/mob.2002.125896
genome to bear on new diagnostics, therapeutics, and cures for human disease. Equally disconcerting to the biomedical research enterprise is the lack of sustained success of physician-scientists in securing research funding. It is no secret that clinical research grant applications fare less well in peer review than their basic science counterparts, particularly in study sections in which both basic and clinical research grants are reviewed. Indeed, individuals who are involved in the ongoing efforts to reorganize the NIH Center for Scientific Review study sections are grappling with how to provide the best review environment for clinical research applications. Tied into this conundrum is how best to transfer knowledge effectively and efficiently from the laboratory to the bedside and alternatively from the clinical environment to the bench. Couple the low success rate of grant applications submitted by clinical investigators with the declining number of physician-scientists, and one can envision easily a situation that harbingers a future with little or no translational research. The Reproductive Sciences Branch (RSB) in the Center for Population Research at the National Institute of Child Health and Human Development (NICHD) is the 1087
1088 DePaolo and Leppert
main funding unit within the NIH that provides support for biomedical research in the reproductive sciences. Cognizant then of the impending shortage of physicianscientists in obstetrics, gynecology, and woman’s health and of the need to bolster translational and clinical research, the RSB set out in the 1990s to create new research and research training programs that could address both deficiencies. These programs include the Specialized Cooperative Centers Program in Reproduction Research, the National Cooperative Program for Infertility Research, the Reproductive Medicine Network, the Reproductive Scientist Development Program, the Women’s Reproductive Health Research Career Development Centers Program, and the Contraception and Infertility Research Loan Repayment Program. This article will provide a brief overview of each program and will describe how the programs collectively seek to create an infrastructure to produce the next generation of physician-scientists and to provide a platform for information exchange between basic and clinical investigators. Specialized Cooperative Centers Program in Reproduction Research The Specialized Cooperative Centers Program in Reproduction Research (SCCPRR) was created in 1998 in response to a perceived need to increase translational research efforts in the reproductive sciences. The SCCPRR is a research-based center program that was designed to promote multidisciplinary interactions between basic and clinical scientists so that breakthroughs in our fundamental understanding of key reproductive processes are translated into clinical practice and so that questions that arise in the clinic may be addressed expeditiously in the laboratory. To ensure efficient transfer of knowledge between the clinic and laboratory, the SCCPRR is administered through a series of cooperative agreements, with each awardee institution using the U54 Specialized Cooperative Research Award mechanism. Currently, there are 14 centers in the network. The breadth of research covered by the SCCPRR is commensurate with the expansive research mission of the RSB. For a center to be funded, at least 3 research projects (including 1 project with a clinical focus) and an administrative core must be approved by the review committee. Other than those funding requirements, the investigator is given the flexibility to design a program that best suits the collective needs of the center. For example, centers may establish consortium arrangements with outside institutions that include foreign sites. Moreover, technical cores can be configured to service only the approved research projects (closed access) or to service those projects and other funded projects within the RSB mission research areas at the awardee institution (open access). In the case of a unique or expensive technology, the institu-
October 2002 Am J Obstet Gynecol
tional core is allowed to provide service to investigators at other SCCPRR centers sites. An important role for NICHD staff in coordinating research activities of the SCCPRR is to help identify and facilitate across-center collaborations and to identify potential opportunities for collaborations with outside entities, such as industry. One means to promote intercenter collaborations has been the establishment of Research Focus Groups in 4 high-emphasis reproductive science areas; endometrial function and dysfunction, ovarian physiology and pathophysiology, male reproduction, and neuroendocrine/pituitary function. Membership of these focus groups consists of a mix of basic and clinical investigators. These groups have been given the opportunity to submit collaborative research initiatives as a means of supporting collaborative efforts amongst SCCPRR centers. Thus far, these initiatives have focused on applied and clinical research in the areas of female contraceptive– lead development, endometriosis, and premature ovarian failure. A fifth focus group, resources/bioinformatics, apprises NICHD of resource/informatics needs of the SCCPRR. As a result of its recommendations, the SCCPRR supports the operation of 4 human tissue banks, 1 nonhuman primate tissue bank, a microarray core facility, and a laser capture microdissection facility. These resources are housed at various center sites in the SCCPRR network and are available to all SCCPRR investigators. Finally, the SCCPRR has supported the establishment and continues to support the maintenance of 2 online databases that deal with the ovary (http://ovary. stanford.edu/) and male reproductive genetics (http://mouse.genetics.washington .edu/). (For further information on the SCCPRR, visit http://reprobio.stanford.edu/sccprrnet/index.html.) National Cooperative Program for Infertility Research In 1991, the National Cooperative Program for Infertility Research (NCPIR) was created in response to legislative directives included in the deliberations of the 101st Congress that stressed the need to enhance support for research on the diagnostic and therapeutic aspects of human infertility alleviation. The NCPIR pioneered the use of a NIH cooperative agreement mechanism (U54) that is now used to administer the SCCPRR. Two centers, 1 at Massachusetts General Hospital and 1 at the University of Michigan, were supported between 1991 and 1996. The current NCPIR sites include Massachusetts General Hospital and the University of Pennsylvania. During the first 5-year period, projects at both center sites represented a blend of basic and clinical research. However, funded projects at the current NCPIR sites almost exclusively involve patient-oriented research with emphasis on the genetic basis of polycystic ovarian syndrome. The NCPIR also provides a stellar research environment for the training of clinical residents and fellows and for ju-
Volume 187, Number 4 Am J Obstet Gynecol
nior faculty members who were seeking additional research training. Similar to the SCCPRR, applicants for NCPIR awards can format their center structure to maximize their strengths. Reproductive Medicine Network The Reproductive Medicine Network (RMN) was established in 1990 to carry out large, multicenter clinical trials in the areas of male and female infertility and reproductive diseases and disorders. Results of these trials are expected to have immediate impact in clinical practice settings. There currently are 8 clinical sites participating in the network and 1 data coordinating center. As with the SCCPRR and NCPIR, the RMN is administered as a cooperative agreement with the U10 Cooperative Clinical Research Award mechanism. Decisions regarding topic areas to be studied, protocol design and execution, and publication of results are made by a steering committee comprised of the principal investigators of the clinical and data coordinating sites, NICHD staff, and an independent chairperson. An independent Clinical Trials Advisory Board assists the choice of topics to be studied and in priority setting. In addition, NICHD has appointed a Data and Safety Monitoring Committee to the network. Thus far, the network has completed 1 protocol that compared intrauterine versus intracervical insemination in couples in whom the female partner was apparently normal. Ongoing protocols include comparison of semen analyses from male partners of infertile couples and the usefulness of endometrial biopsy in infertility treatment, including an interobserver variability study. A clinical trial of the use of metformin versus metformin and clomiphine citrate versus clomiphine citrate in the treatment of polycystistic ovarian syndrome has been launched. Additional information can be obtained at http://rmn.deri.duke.edu. Reproductive Scientist Development Program The RSB participates in a private sector career development program for obstetrician-gynecologists, the Reproductive Scientist Development Program. Partial support for the program is from a Mentored Research Scientist Development Program Award (K12). The program independently recruits and selects its own candidates. Participants undertake a phase I research experience under a basic science mentor, with the second and third phases the initiation of an independent research program at the sponsoring institution. Women’s Reproductive Health Research Career Development Centers Program Established in 1998, the Women’s Reproductive Health Research (WRHR) centers seek to support the research career development of obstetrician-gynecologists by bridging clinical training with a career in basic, transla-
DePaolo and Leppert 1089
tional, and/or clinical research that is relevant to women’s reproductive health. The Mentored Clinical Scientist Development Program Award (K12) is used to administer this program. The award is given to academic medical institutions to enable these institutions to provide a nurturing environment for the training of physician-scientists for a career conducting research in obstetrics/gynecology and/or its subspecialties (such as maternal-fetal medicine, gynecologic oncology, reproductive endocrinology) and emerging subspecialties (such as urogynecology). The institution recruits and selects its own scholars contingent on NICHD approval. These awards provide salary support for mentors, WRHR scholars, and technical staff and funds for supplies and equipment. As with NIH K awards in general, the support of scholars through the WRHR program provides release time from other clinical and teaching responsibilities. Currently, the NICHD with cosponsorship from the NIH Office of Research on Women’s Health supports 20 centers from around the country. Contraception and Infertility Research Loan Repayment Program In 1997, the NICHD announced the availability of a loan repayment program for educational loan debt under the auspices of the NICHD Contraception and Infertility Research Loan Repayment Program (CIR-LRP). The program, authorized by Section 487B of the Public Health Service Act as amended by Public Law 105-392, provides for the repayment of educational loan debt of qualified health professionals (including graduate students) who agree to commit to a period of obligated service of not less than 2 years conducting research with respect to contraception and/or infertility. According to laws that regulate Federal LRPs, the CIR-LRP pays up to $35,000 of the principal and interest of a participant’s educational loans for each year of obligated service and will reimburse participants an amount equal to 39% of the tax liability as a result of the repayments being reported as income. The purpose of the CIR-LRP is the recruitment and retention of highly qualified health professionals who conduct contraception and/or infertility research. With its inception in 1997, the CIR-LRP became the first NIH LRP for extramural investigators. Participation in the CIR-LRP is limited to individuals who, at the time of participation, are in employment/ training at an NICHD intramural laboratory or an NICHD-supported extramural site, which includes centers that belong to the SCCPRR, NCPIR ,and WRHR programs and clinical or data coordinating units for the RMN. From 1997 through 2001, the CIR-LRP has executed 38 contracts. Thirty-one of these participants have been affiliated with either the WRHR (12 participants), SCCPRR (9 participants), or NCPIR (5 participants) centers or the RMN (5 participants).
1090 DePaolo and Leppert
Additional information regarding the CIR-LRP can be obtained at http://www.lrp.nih.gov/about/extramural/CIR/index.htm. The Infrastructure Now that we have presented a brief overview of the individual components, it is time to examine how each component and the interplay of components can create an infrastructure to enable the successful pursuit of translational and clinical research by an increased cadre of physician-scientists. One of the key components in increasing the number of clinical investigators is the CIRLRP. Faced with an enormous educational debt, many recently-trained medical doctors do not even consider a career in research. The CIR-LRP has enabled some clinicians to at least taste the fruits of the research environment without having to worry about paying their loan debt. Indeed, it is no surprise that almost 70% (26/38 participants) of CIR-LRP participants have held the MD or joint MD-PhD degrees. Hearing the LRP participants speak of being able to raise families and have mortgages because of their participation in the LRP has meant that this program has made a substantive difference in the lifestyles of these young clinicians. The training grounds for many of the LRP participants and others have been the programs that were described earlier. Most important among these are the WRHR centers. These centers give the clinician scholars-in-training their first extensive exposure to research design and methods and how to deal with patients as human subject participants in clinical studies rather than just patients. In some cases, exposure of the WRHR scholars to basic, translational, or clinical research has been in the laboratories of investigators who belonged to the SCCPRR or NCPIR because WRHR centers have been awarded to 6 institutions that are SCCPRR center sites (or consortium sites for the SCCPRR) and 2 institutions that are NCPIR center sites or, at least, affiliated with a NCPIR site, as is the case for the Harvard University system of hospitals. Fi-
October 2002 Am J Obstet Gynecol
nally, some scholars have been given the opportunity to participate in the design, conduct, and analyses of clinical trials through the RMN. Although perhaps not by design, the SCCPRR, NCPIR, and RMN represent the 3 cornerstones of the clinical research infrastructure, namely the basic/translational component (SCCPRR), the clinical hypothesis–oriented research component (NCPIR), and the clinical trials component (RMN). Because no one program can take basic research knowledge directly into the clinic, efficient translation of basic research into clinical practice requires interactivity of programs. In 1 example, a recent protocol has been approved for phase I clinical trials in the RMN on the basis of a study that was conducted by SCCPRR investigators at the University of Virginia on the use of metformin to induce ovulation in clomiphene-resistant women with polycystic ovarian syndrome. It is likely that the RMN will tap SCCPRR and NCPIR sites to help recruit patients into the clinical trial, particularly as it pertains to individuals from special or diverse populations. In yet another example, basic scientists from the SCCPRR are collaborating with clinical investigators from the NCPIR in examining the role of the fragile X mental retardation gene in the cause of premature ovarian failure. In closing, the RSB has been visionary and perhaps fortunate (ie, Congressional directives to establish the NCPIR and CIR-LRP) in its creation of programs that individually are strong and collectively are poised to support translational and clinical research efforts and to build a well-trained cadre of physician-scientists to do the research well into the 21st century. We propose that the collective use of these types of programs be used as a model by NIH staff in scientific areas in which similar deficiencies can be identified. REFERENCE
1. Rosenbert L. Physician-scientists: endangered and essential. Science 1999;283:331-2.