NIH/NICHD – Reproductive Medicine Collaborative Clinical Trials Program (Collaborative R01 Clinical Trial Required)

October 30, 2018 by School of Medicine Webmaster

The purpose of this funding opportunity announcement is intended to support a collaborative program of linked clinical trial sites including data coordination. These linked sites will be referred to as ‘consortia’. Each consortium will consist of at least two linked clinical sites, all of which will carry out a unique clinical protocol designed to facilitate advances in diagnostic and therapeutic solutions to infertility, and of which at least one site includes data coordination expertise and functional capability, and who have agreed to oversee and implement the same protocol.

Infertility, defined as the inability to conceive after 12 months of trying, affects approximately 7-15% of reproductive-aged couples.  Most interventions to treat infertility, especially those pertaining to male infertility and in vitro fertilization, have been empirical with insufficient evidence-based research to support the approach.  Well-designed multi-site clinical trials provide a means to develop high-quality evidence addressing important questions in male and female infertility and translate new discoveries into the clinical arena. Moreover, the development of new medications and technologies requires evaluation for safety and efficacy that is best achieved through large-scale clinical trials.  This, in turn, will result in scientifically substantiated, safe, more efficient, and cost-effective care.

Previously, NICHD Program staff cooperatively assisted in identifying research topics of high priority and in designing and implementing protocols to evaluate the optimal management in the areas targeted for research. As the NICHD Reproductive Medicine Network has matured, the current program seeks PD(s)/PI(s) that have self-identified and have congruent interests to develop a common protocol to answer important questions regarding diagnosis or treatment of female and male infertility, which they seek to implement. The objective of this program is to support the conduct of multi-site trials in reproductive medicine by establishing linked research awards to form clinical research consortia that can perform rigorous patient evaluation, recruit adequate numbers of patients, and collect and analyze large data sets to provide answers more rapidly than individual sites acting alone.  The diagnostic and intervention research covered under this announcement is explicitly focused on practice-relevant questions with the goal to provide evidence that guides clinical practice.


The Reproductive Medicine Network (RMN) was established by NICHD in 1989 to address the need for large, multicenter clinical trials to study infertility and reproductive diseases and disorders that impact fertility, in order to increase the evidence-base for infertility treatments. In the last 30 years, the RMN has made significant advances in addressing the gap in evidence-based medical approaches.  Yet, in this time of rapidly evolving scientific knowledge specifically in the realms of genetics, genomics and precision medicine, the need to conduct trials that evaluate new diagnostic methods and identify the most effective interventions for both male and female infertility still remains.

For the current award period which commenced in 2013, three trials have been/are being conducted:  1. Active Treatment or No Treatment: Optimal Treatment for Women with a Persisting Pregnancy of Unknown Location – A Randomized Clinical Trial of Women at Risk for an Ectopic Pregnancy (ACTorNOT), 2. Improving Reproductive Fitness with Pretreatment with Lifestyle Modification in Obese Women with Unexplained Infertility (FIT-PLESE), and 3. Males, Antioxidants and Infertility (MOXI). Observational studies undertaken by the RMN have addressed Psychological Family Issues and Outcomes of Multiple Gestations (PsyFI).  In addition, the ENDOmarker study is establishing a biorepository of well-characterized patient data and samples for future use to develop serum or tissue biomarkers for the diagnosis of endometriosis. In prior funding cycles, studies addressed new medications for ovulation induction in infertile women with polycystic ovary syndrome (PCOS), compared two existing standards of care utilized in in vitro fertilization (IVF), and evaluated existing treatments for unexplained infertility on the primary outcome of multiple gestations. (See

As a byproduct of conducting these trials, the RMN has also collected additional data, including behavioral outcomes and quality of life measures, and biospecimens during the conduct of the clinical trials that serve as a resource to the scientific community at large by providing access for scientific studies through the RMN biorepository via the NICHD Data and Specimen Hub (DASH).  The RMN has also supported a Pregnancy Registry replete with follow-up information from offspring born from NICHD-funded infertility trials.

The RMN also provided a platform for exposing interested clinicians to clinical research by collaborating with the Clinical Research Reproductive Scientist Training (CREST) Program which is funded by an R25 grant.  While not a main goal of the program, it is envisioned that these consortia will continue to serve as a resource for the training of CREST scholars by enabling them to utilize the intellectual and research infrastructure to become familiar with performing clinical research, performing secondary data analyses and interpreting results from those trials.


This FOA is intended to support a collaborative program of clinical trial sites (i.e, consortia) to advance the scientific research on new medications, interventions and approaches addressing the diagnosis, prevention and treatment of infertility.  A consortium requires participation of two or more collaborative sites for completion of the study. Accordingly, the collaborating studies share a common protocol across the sites and are organized to increase sample size, accelerate recruitment, and increase sample diversity and representation. Each site has its own Program Director/Principal Investigator (PD/PI) and each consortium provides a mechanism for cross-site coordination, quality control, database management, statistical analysis, and reporting. This initiative requires that each clinical site within a self-identified consortium have the resources, infrastructure and clinical capacity to support clinical trials in reproductive medicine.

Topic areas of high program relevance include but are not limited to:

  1. Trials that can contribute to advancing the personalization of reproductive health care and include collection of clinical and biological variables (e.g., blood for genetic analysis, other potential biomarkers), as appropriate, that might be used to inform or test algorithms to foster personalized treatment strategies;
  2. Trials that address medical management of mild male factor infertility/subfertility;
  3. Trials that address comparative effectiveness of current standards of care in IVF to optimize singleton live birth rates while minimizing multiple births;
  4. Evaluation of cost-effective alternatives to current diagnostic methods and interventions for infertility and early pregnancy loss;
  5. Investigation of interventions that maximize fertility and live birth outcomes in women with underlying conditions such as endometriosis, uterine fibroids, or prior pelvic infection;
  6. Investigation of the immunologic aspects of infertility.

Effectiveness of the program will be assessed by: 1) timely completion of clinical trials that address public health concerns in the area of infertility; 2) the tempo of recruitment and synergy of multiple primary sites; 3) the quantity (numbers of publications) and quality (impact on clinical practice) of publications emanating from the trials, and, to a lesser extent, 4) further use of resources generated from trials (i.e., biospecimens, data) by outside investigators that contributes to advancing scientific knowledge and improving health care.


Applications for this FOA should include investigators who possess the knowledge and expertise in conducting clinical trials in the field of reproductive medicine, with expertise in female and/or male infertility and/or reproductive diseases and disorders that impact fertility.

Investigators should have sufficient expertise, commitment of effort, organizational structure, and operational effectiveness to successfully implement a plan for this undertaking. It is expected that within each consortium, investigators will be from a variety of professional backgrounds and have interdisciplinary research expertise . Examples of the kinds of investigators who could be included in the consortium include reproductive endocrinologists, reproductive urologists, andrologists, endocrinologists, bioinformation specialists, epidemiologists, biostatisticians, clinical trialists, gynecologists, radiologists, pelvic surgeons, and psychologists, to name a few.

A multiple Program Director/Principal Investigator model of leadership may be proposed if warranted.


Applicants are expected to propose a consortium of investigators that span multiple institutions, linked by a common clinical trial protocol. A successful consortium will likely have an organizational structure that effectively addresses the proposed aims and integrates the personnel, resources, and infrastructure across institutions. Examples of the organizational components that could contribute to a successful consortium include a leadership or steering body composed of the PDs/PIs of the linked sites to coordinate planning, evaluation, resource allocation, and administrative oversight. The consortium may identify a mentorship committee that facilitates involvement of junior investigators into the research activities of the consortium and a dissemination committee that coordinates timely and effective information sharing with relevant stakeholders. Applicants may also consider establishment of an external advisory committee. These are merely examples and are not intended to prescribe a specific organizational structure. Investigators may propose the components and functions that best suit the aims of the consortium.

The consortium must identify one site that will provide data coordination functions.  These functions include: 1) assistance in the implementation of the clinical protocol, monitoring of clinical sites and distribution of protocol (capitation) costs to the clinical sites; 2) provision of clinical and scientific knowledge to facilitate data collection and analyses and drafting of case report forms, consent forms, annual reports by the consortium and other reports and documents as needed to support the goals of the consortium clinical sites and this program; 3) facilitation of regulatory requirements such as adverse event reporting and coordination of serious adverse event reporting and resolution between the clinical consortium sites and Data and Safety Monitoring Board (DSMB); 4) provision of scientific knowledge necessary to facilitate IND submissions and communications with the FDA; 5) provision of logistical services to the consortium members as required by the multi-site research program; 7) assistance with the preparation of single IRB submissions, amendments and reports, and 8) preparation and coordination of DSMB reports and regular DSMB meetings.

The consortium through the data coordination body is expected to have procedures and capabilities for standardization and exchange of data, as well as housing informatics resources, biospecimens, and other research resources. As such, a mechanism should be proposed for the following: 1) providing patient care costs to clinical sites and monitoring expenditures by sites and forming and issuing sub-contractual arrangements to ancillary recruitment sites; 2) facilitating the centralization and standardization of the data that are derived from collaborative studies and putting the data into a common format for use by the consortium member sites, as well as preparation of data into a format to be deposited into the NICHD data repository DASH, 3) facilitating the transfer and the archiving of data generated to preserve the data for future secondary analyses and for access by the outside community through deposit of data into the NICHD DASH.

Applications should include plans for coordination, communication, publishing and data sharing.  They should also describe the functions of the coordination site, how the DSMB will be constituted and plans for the single IRB.

A webinar with NIH staff will be planned to provide prospective applicants the opportunity to receive information and ask questions about the scientific scope of this announcement and technical details for applying.  We anticipate the webinar will be held late November or early December 2018.

Deadline:  December 18, 2018 (letters of intent); January 18, 2019 (full proposals)


Filed Under: Funding Opportunities