to see the attendee. Yeah, you can see the participant number go up. Okay. Can I see that? I don't see it. It's on the bottom bar. Data, Rebuild Academic Success in Urogynecology by Dr. Donna Maslamdoust. Dr. Maslamdoust will present for 45 minutes. The last 15 minutes of the webinar will be dedicated to the Q&A. Dr. Maslamdoust completed her medical training at Emory University School of Medicine and pursued an OBGYN residency at the University of Cincinnati. Upon graduation, she joined the faculty at Georgetown University Hospital in Washington, DC, where she also served as an assistant clerkship director for the medical students. She left Georgetown to pursue fellowship in female pelvic medicine and reconstructive surgery at the Tricare Health Good Samaritan Hospital. She's currently clinically active at Mid-Atlantic Urogynecology, associated with the NOAA Fairfax Hospital outside of Washington, DC, and is an assistant program director for the Walter Reed FPMRS Fellowship. She joined the NIH Eunice Kennedy Shriver National Institutes of Child Health and Human Development in 2017 as a medical officer and project scientist for the Pelvic Fluor Disorders Network, overseeing the research conducted by the Pelvic Fluor Disorders Network. Before we begin, I'd like to review some housekeeping items. This webinar is being recorded and live streamed. Please use the Q&A feature of the Zoom webinar to ask any questions for the speaker. Use the chat feature if you have any technical issues and the AUG staff will be monitoring the chat and can assist you. And Dr. Muslim-Jus, it's all yours. All right. Can you guys hear me okay? No. You can or you cannot? Yes. You can, okay. All right, great. So thank you for allowing me to be here tonight to present this information. And we'll go ahead and get started. I have no relevant disclosures. So the objective of this talk will be to understand the historical perspective behind research regulation and why public access was initiated. I also hope you will learn about publicly funded research and the resources available to the public. And finally, we will attempt to understand big databases and how to use this available data for secondary analyses. So while original data is intriguing and exciting, often the work may have already been performed and investigators can borrow from previously collected data to answer new questions. Historically, there was a concern that for financial reasons, medical information obtained through studies was not being shared. Government regulations now mandate federally funded research to be registered and clinicaltrials.gov and the data to be ultimately shared. As a result of this resource sharing, investigators now have access to these large databases or what we sometimes refer to as big data and that can be utilized to answer important clinical questions. New and such opportunities. So human subjects research is critical to advancing the understanding of human pathologies and enhancing medical care. Yet subjects involved are asked to incur potential risks from which society may ultimately benefit. So ethical principles are therefore imperative to protect the rights of research participants. Prior to formalized research, medical treatments were mostly experimental as large data rarely existed. Much of medical ethics at this point relied on the Hippocratic Oath and while most investigators likely had good intentions, concerns over deception, self-interest or exploitation eventually led to a need for regulations. So some regulations were in response to specific situations while others were obtained as new information was obtained. One of the first experiences was in 1901 where 13 children in St. Louis died from diphtheria antitoxin contaminated with tetanus force. This prompted Congress to pass the Biologics Control Act and between 1903 and 1907 standards were established. Any pharmaceutical firms hoping to manufacture vaccines, antitoxins, antibacterial, antiserum and other similar topics were required to obtain licenses. These standards led investigators into new fields such as immunology which evolved to better understand sudden deaths following repeated injections of biologics prepared in foreign protein media such as horse serum. The Food and Drug Act also known as the Wiley Act was signed by President Roosevelt in 1906. This paved the way for the regulatory and first consumer protection agency, the Food and Drug Administration. It prohibited the transport or sale of altered or mislabeled food or drug products between states and required food and drugs to have labels of active ingredients. So despite the attempted protections laid forth in the act in 1937, a Tennessee drug company called S.C. Massengill Company marketed an untested new sulfa drug geared towards children. The drug was found to be a toxic analog of antifreeze and resulted in over a hundred deaths, many of whom were children. This prompted Congress to pass the Food, Drug, and Cosmetic Act in 1938, which mandated pre-market approval of all new drugs. A sad historical review of this episode showed that the company owner offered no responsibility towards what had happened. When asked to admit culpability, he infamously answered, we have been supplying a legitimate professional demand and not once could have foreseen the unlooked for results. I do not feel that there was any responsibility on our part. The chemist, however, who developed the product, Harold Watkins, committed suicide while awaiting trial. He reported that he was not aware the solvent was poisonous. The toxicity of the solvent was first published in 1930, but medical knowledge was not as widely shared as it is today, resulting in this tragedy. In 1972, the nation was shocked by the revelation of the U.S. Public Health Service Tuskegee syphilis study. Many of you should be probably familiar with this. The study initiated in 1932 by the Public Health Service with the intent to study the natural history of syphilis. It enrolled 399 African-American men from Macon County, Alabama at the Tuskegee Institute with syphilis, along with 201 men who were disease-free. The men were promised medical examinations, meals and burial insurance free of charge as an incentive to participate. The study was scheduled to last six months, but continued for 40 years. And while hundreds of African-American men had intervention deliberately withheld, even once penicillin became the accepted treatment. An advisory panel was convened from the public outcry and found that the men had been misled and were not properly provided with informed consent. Publicity surrounding this ultimately led to enough public scrutiny that Congress passed the 1974 National Research Act. And the 1974 Act convened the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was charged to identify basic ethical principles and develop guidelines for the conduct of research involving human subjects. The Belmont Report, where some of you might have to read about when you're doing your trainings, was developed and described the following basic ethical principles necessary in research, number one, respect for persons, number two, beneficence and number three, justice. So influenced by the Belmont Report in 1991, the Common Rule was published and required research funded by 17 federal agencies to comply with this federal policy for the protection of human subjects, which outlines provisions for human subjects protections, institutional review boards, informed consent and assurances of compliance. So why talk about this history? First of all, it's just interesting, a lot more than the other stuff I'm about to talk about. So just like bringing up, but also we need to learn from our mistakes. It also helps to demonstrate how and why the government became involved in research regulation, because we probably take this for granted since it has existed for the majority of our careers. And finally, it is what paved the way towards data sharing policies. So a little bit about NIH's history as well. Its roots stem from the Marine Hospital Service or MHS, which also led to the development of what is now the Public Health Service. MHS was established in 1798 to provide medical care for merchant seamen and was charged by Congress to examine passengers arriving on ships for infectious diseases such as cholera and yellow fever to help prevent epidemics. In 1887, an MHS physician, Joseph Kinyon was authorized to set up a one-room laboratory in Staten Island, New York. The facility was called the Laboratory of Hygiene and later referred to as the Hygiene Laboratory. It was intended to replicate the German facilities that serve the public's health. In 1891, the Hygienic Laboratory was moved to Washington, D.C. And in 1901, it was recognized in law where Congress authorized $35,000 for construction of a new building, which was a lot of money at that time. The laboratory was charged with the goal to investigate infectious and contagious diseases and matters pertaining to the public health. Some of the lab's early work were during World War I, where they discovered that the anthrax outbreaks among troops at the time traced back to contaminated shaving brushes, as well as the fact that bunion pads widely used to cover smallpox vaccinations could harbor tetanus spores. In 1918, the laboratory was put to test as the influenza pandemic hit Washington, D.C. The Hygienic Laboratory physicians were pushed into service to treat patients as local doctors fell ill, much as how the NIH has guided a lot of what's gone on through COVID. Recognizing the importance of the need for the Hygiene Laboratory, Congress acted. After no sponsors were found to endow the Institute, Louisiana Senator Joseph E. Ransdell and proponents sought federal sponsorship in 1926. And in 1930, the Ransdell Act changed the name of the Hygiene Laboratory to the National Institute of Health at that time. This act demonstrated an attitude shift in the U.S. scientific community towards public funding of medical research, which was a newer concept at that time. The NIH started as one Institute, and now it holds 27 and is referred to as the National Institutes of Health. It is the largest public funder of biomedical research in the world and funds billions of dollars in the U.S. and across the globe annually. Greater than 80 Nobel Prizes have been awarded to NIH-supported research, five of those to intramural NIH investigators, which I'll touch upon. Successes of NIH-funded research include deciphering the genetic code, establishing a greater understanding of genetically-based diseases, development of drugs designed to target specific proteins and disease processes, improved cancer treatments, reduction of death from heart attack and stroke, and preventative strategies reducing the need for expensive therapeutics. So because of its large influence, NIH policies can impact many researchers. Investigators may be bound to NIH policies because their institutions receive NIH funding. So for example, the common rule applies to all researchers at institutions receiving any NIH funding, even if that researcher is not themselves receiving that NIH funding. So it is important to know of your institution's guidelines. In 2003, NIH published a statement on sharing research data, which described the NIH expectation and support of the timely release and sharing of final research data from any NIH-supported studies for use by other researchers. This would be anticipated to be submitted no later than the acceptance for publication of the main findings from the final data set. The statement at that time applied to any applications with direct costs greater than $500,000 in any single year. However, in 2015, NIH issued an update for its plan that all NIH-funded researchers prepare data management plans in their applications. In August of 2007, a second policy for sharing data was released regarding genome-wide associated studies, or GWAS. A genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits, such as blood pressure or weight, or the presence or absence of a disease or condition. Consistent with the NIH mission to improve public health through research, the NIH believes that the full value of GWAS to the public can be realized only if the genotype and phenotype databases are made available as rapidly as possible to a wide range of scientific investigators. The data will be available in the data repository. NIH initially proposed that the GWAS datasets would be made available as soon as appropriate quality control measures were complete. NIH does expect that investigators who contribute data to the NIH GWAS data repository will retain the exclusive rights to publish analyses of the dataset for a defined period of time following the release of a given genotype-phenotype dataset through the NIH GWAS data repository. So during this period of exclusivity, the NIH will grant access to other investigators who may analyze the data, but are expected not to submit their analyses or conclusions for publication during that exclusivity period. And while NIH initially suggested a nine-month period of exclusivity in response to concerns raised through the public comment process, NIH lengthened this period to 12 months in its final policy. NIH issued the Genomic Data Sharing Policy in August of 2014. The policy applies to all NIH-funded research that generates large-scale human or non-human genomic data, regardless of the funding level, as well as the use of these data for subsequent research. NIH will release data submitted to NIH-designated data repositories no later than six months after the initial data submission begins or at the time of acceptance of the first publication, whichever occurs first, without restrictions on publication or other dissemination. And finally, NIH published guidelines for research conducted in the intramural division, that is, the research that is performed and located at the NIH campus in Bethesda. The guideline became effective October 1st, 2015, and mandates that a data-sharing plan must be developed for any research involving human data. Data-sharing plans will be included in the Institute's scientific review process for research involving human data. All clinical investigators are expected to develop protocols and consent processes or forms to enable broad data sharing for the secondary research consistent with this policy. All intramural investigators are encouraged to deposit data in publicly accessible research repositories for sharing to the extent feasible and appropriate. The policy included data shared among intramural investigators, as well as data shared with the public. And ultimately, both federal and NIH initiatives require all federally funded research datasets to be publicly available. So in 2013, the director of the White House Office of Science and Technology Policy issued a memo to all agencies and department heads, directing federal agencies with more than $1 million in annual conduct of research and development to develop plans for increasing public access to peer-reviewed scientific publications, as well as digital data resulting from federally funded research investments. In an executive order in May of 2013, President Obama declared that government information shall be managed as an asset throughout its life cycle and wherever possible and legally permissible to ensure that data are released to the public in ways that make the data easy to find, accessible, and usable. And those three things are very important. And basically, NIH expects and supports timely release and sharing of final research data from any NIH-supported study for use by other researchers. And this typically means by publication or no later than 12 months. So DASH, which stands for the Data and Specimen Hub, was created for NICHD, which is my institute, to house federally funded data. The purpose of DASH was to make available any federally funded study which ultimately maximizes NIH's investment in research studies through the promotion of data sharing, so basically getting two studies out of one funding if possible. Importantly, NICHD has a broad research portfolio. There are over 2,000 clinical research studies conducted annually, which generate a large wealth of data that can be utilized for primary or secondary scientific discovery. Furthermore, DASH addresses current data sharing challenges. So, for example, data may be stored in silos or in different physical locations and also on a variety of different devices. Often the storage locations are not cataloged, and the data may also be stored in different formats and structures without uniformity, making it difficult to share easily. The purpose of DASH was to comply with the federal and NIH policies, as we just discussed. Not all NICHD-funded studies have to submit to DASH. They just provided this as an easy avenue where investigators could submit their data and make it publicly available more easily. So DASH provides this publicly accessible, centralized resource for researchers to store and access de-identified data from NICHD-funded studies for use in secondary research. It provides a mechanism for this funded extramural and intramural investigators to share their research data from studies and comply with the NIH data sharing policies, as well as the NIH genomic data sharing policies. It's governed by the DASH committee, which is composed of representatives across divisions, branches, centers, and offices of NICHD, like myself. And ultimately, DASH does hope to include the ability to view and request associated biospecimens, as well as connect with related databases, view and use analytical tools, and visualize data as well. So how does the submission process work? The investigator obtains institutional approval and then submits the de-identified data to DASH. This goes through the committee to verify that the data is appropriately de-identified, which is a multi-step, very complicated process. Once it is approved, the NICHD division director or branch chief signs off, and then the data is posted to the DASH website. Requesters are required to submit something called an online data request form, a data use agreement, and IRB approval if it is available. While it says optional, it's recommended. Data request approvals are granted by the DASH data access committee, as well as any provisional study-specific approvals, such as a steering committee, API, that needs additional approval. Once the data request package is received, it's reviewed by the DASH data access committee. If approved, it then proceeds to any further approval by any other providers as necessary. Once the request is approved, the data is then provided to the applicant. The data use agreement is executed between the recipient and NICHD. It's valid for three years, and it is renewable in case you don't accomplish what you intended to in that time. The terms of the agreement require the participant to use data only for the approved research. The data can't be shared with anyone who's not listed in the request. There should be no attempt to identify the individuals in the study. The recipient must follow all applicable laws, regulations, and local institutional policies and procedures for handling data, and any violations of the data use agreement must be reported. Furthermore, the requester must acknowledge the contribution of the data submitter, as well as NICHD DASH with regard to any publication or intellectual property, and must also provide annual progress reports on research using DASH data. There's currently 191 studies available within DASH, with nine studies offering biospecimens. Remember that the biospecimens aren't actually housed within DASH, so they would have to be obtained from the physical site in which they're stored, but DASH offers a catalog, which is still a work in progress. 50 study topics are available, including PFDs. You can Google DASH or go to this website if you're unfamiliar with this website. The icon here in the lower left can provide an overview. You can then search by topic, study type, or other filters to find studies that are available. You will need to sign up if you haven't done so before in order to make any requests. So for those of you who may be unfamiliar with the Pelvic Floor Disorders Network, or PFDN, NICHD established PFDN in 2001 to encourage collaborative research on pelvic floor disorders. PFDN includes eight clinical centers and a data coordinating center, or DCC, located at U.S. universities and medical centers. The grant was just renewed October of last year for another five-year cycle to begin July of this year. And the PFDN boasts numerous multi-centered randomized controlled trials, many publications, and some of these studies are available on DASH. So we're gonna go through that here next. Currently, there's nine studies performed by the PFDN whose data is easily available to you on DASH that can be used for any secondary analyses. Biospecimens are also available, but we are still working on the availability of these specimens. And again, they have to be requested directly through the PFDN at this time. We're gonna go through each of these studies just so that you have an idea of what was studied and what data might be available. The slides are pretty dense. So just hang in there with me. Let's start with the CARE trial, which was designed to assess whether the addition of standardized birch-pulpo suspension to open abdominal sacroculpopexy decreased postoperative stress urinary incontinence in women without preoperative symptoms of stress incontinence. So women who didn't report symptoms of stress incontinence and chose to undergo sacral colpopexy were randomly assigned to concomitant BIRCWH versus a sham procedure. The primary outcome at three months after surgery was stress urinary incontinence. And at three months postoperatively, 33.6% of the women in the BIRCWH group and 57.4% of the controls met one or more of the criteria for stress incontinence, showing that a concomitant BIRCWH procedure would help reduce postoperative stress urinary incontinence in asymptomatic women. So next, CAPABLE compared the use of loperamide to oral placebo and the use of anal sphincter exercise training with biofeedback to usual care, which involved an educational pamphlet in the treatment of women suffering from fecal incontinence. 300 women with at least monthly fecal incontinence over the prior three months seeking treatment were recruited and randomized in a two by two factorial trial to one of four groups. So either placebo and education, placebo and feedback, loperamide and education, or loperamide and feedback. The primary outcome was the St. Mark's symptom scores, which were measured at 12 and 24 weeks. At 24 weeks, the change in St. Mark's scores from baseline didn't differ between the individual intervention groups compared to the placebo and education groups. Esteem aimed to estimate the effect of combined mid urethral sling and perioperative behavioral and pelvic floor therapy compared to sling alone on the successful treatment of mixed urinary incontinence symptoms. The primary outcome was change in mixed urinary incontinence symptoms 12 months postoperatively based on the total UDI score. Secondary outcomes included stress and urgency incontinence symptoms based on UDI stress and irritative subscale scores, three day bladder diary, a patient global impression of improvement in severity and the incontinence impact questionnaire scales. The results demonstrated that although sling improved mixed urinary incontinence symptoms, combined sling and physical therapy is associated with greater improvement in urinary symptoms and quality of life compared to sling alone. And there is some caveat about it meeting the minimally important difference. HMS Esteem, which was an offshoot, described the role of the urinary microbiome plays in the disorders of the lower genital urinary tract. It compared the urinary microbiome in women with mixed urinary incontinence to similarly aged controls. Catheterized urine specimens were obtained and the V4 to six regions of the 16S rRNA gene were sequenced to identify bacteria. Bacterial predominance was compared between mixed urinary incontinence and controls. 123 MUI and 84 controls were analyzed. The DNA sequence reads from urine and vagina DNA have been uploaded to the MCBI sequence read archive and are available. The results showed that women with MUI and controls didn't differ in lactobacillus predominance. However, in younger women, urinary bacterial community type differentiated MUI from controls. Optimal compared sacrosplenous ligament fixation to uterus sacral vaginal vault ligament suspension and also assess the role of perioperative behavioral therapy and pelvic muscle training in women undergoing vaginal surgery for apical and uterine prolapse, as well as stress urinary incontinence. Women were randomized to either a sacrosplenous versus uterus sacral ligament suspension, then randomly assigned to either receive the physical therapy or not. The physical therapy was before and after the surgery and the primary outcome for the surgical intervention was surgical success. For the behavioral component, the primary outcome was urinary symptoms at six months, as well as prolapse symptoms at two years. And the results at two years showed that neither uterus sacral nor sacrosplenous ligament suspension was significantly superior to the other for anatomic, functional or adverse event outcomes. Perioperative pelvic muscle training also did not impact urinary symptoms at six months or prolapse outcomes at two years. E-Optimal was the extension of this study of Optimal for up to five years postoperatively. The primary aims were to compare the two surgeries up to five years after surgery. The original study randomized 374 patients of whom 309 were eligible for the extended trial and 285 enrolled. By year five, the estimated surgical failure rate was 61.5% in the uterus sacral group and 70.3% in the sacrosplenous group with no statistical difference. The estimated anatomic failure rate was 45.6% in the physical therapy group and 47.2% in the usual care group with again, no statistical difference. There was no difference in improvements in the pelvic organ prolapse distress in the Tory scores between groups. In general, there was no significant difference between the surgeries in rates of surgical failure and no significant difference between perioperative behavioral muscle training and usual care on rates of anatomic success and symptom scores at five years. So compared with outcomes at two years, the rates of surgical failure increased during the follow-up period. However, prolapse symptoms, symptom scores remained improved. Opus examined whether performing a mid urethral sling at the time of vaginal prolapse surgery reduces postoperative urinary incontinence in women without stress urinary incontinence prior to surgery. The primary endpoint was incontinence or treatment for this condition at three months for the secondary primary endpoint at 12 months. Of the 337 women who underwent randomization, 97% completed follow-up at one year. So there's pretty solid data there. At three months, the rate of urinary incontinence or treatment was 23.6% in the sling group and 49.4% in the sham group, which was statistically significant. At 12 months, urinary incontinence was present in 27.3% in the sling group and 43% in the sham groups. The number needed to treat with a sling to prevent one case of urinary incontinence at 12 months was 6.3. And so the conclusions were that a prophylactic mid urethral sling inserted during vaginal prolapse surgery resulted in a lower rate of urinary incontinence at three and 12 months, but ultimately did have higher rates of adverse events. Next, the COBALT-CLAISIS trial was conducted to study the effects of COBALT-CLAISIS on pelvic support symptoms and quality of life and report associated morbidity and postoperative satisfaction. The data collected includes physical examination or responses to the pelvic floor distress inventory, as well as the pelvic floor impact questionnaire. All pelvic symptom scores and related bothers significantly improved at three and 12 months and 95% of the patients said they were either very satisfied or satisfied with the outcomes of their surgery. And the study demonstrated that COBALT-CLAISIS was effective in resolving prolapse and pelvic symptoms and was associated with high patient satisfaction. And finally, ROSETTA. ROSETTA aimed to assess whether Botox is superior to sacral neuromodulation in refractory episodes of urgency urinary incontinence. Patients were randomized to receive either 200 units of Botox versus sacral neuromodulation. The primary outcome was change from baseline mean number of daily urgency urinary incontinence episodes over six months, and these were measured with monthly three-day diaries. Secondary outcomes included change from baseline in urinary symptom scores in the overactive bladder questionnaire short-term, the overactive bladder satisfaction questionnaire, as well as any adverse events. Women in the Botox group had greater improvement in incontinence episodes, as well as greater improvement on the questionnaires. However, the clinical significance of that small decrease in incontinence episodes is uncertain. And Botox did result in higher rates of UTIs as well as the need for self-catheterization. So moving on for a bit, we'll talk about all of us, but I will wanna mention that there are obviously a lot of PFDN ancillary studies. Sometimes it actually helps to look at those ancillary studies, and it might trigger ideas that you can use for other data, but there is a wealth of knowledge that is available to you through the PFDN studies. Another initiative that is coming up is called All of Us. So it's a little bit more recent, but NICHD is participating in this. The historical background is that the National Institutes of Health formed what was called the Precision Medicine Initiative Working Group of the Advisory Committee to the Director in March of 2015. The group concluded its work in September of 2015 with a detailed report, which provided a framework for setting up the All of Us Research Program. All of Us is working to improve healthcare through research, but unlike other research studies that focus on one disease or a group of people, All of Us is building a very diverse database that hopefully can inform thousands of studies on a variety of health conditions. This precision medicine is based on the participant as an individual and takes into account their environment, lifestyle, family health history, and genetic makeup. The goal will be to ultimately give healthcare providers the information they need to make customized recommendations for people of different backgrounds, ages, and regions, which can hopefully reduce healthcare costs by matching the right person with the right treatment for the first time. So All of Us is building a diverse database that can inform thousands of studies, and it is seeking 1 million or more participants from across the U.S., so stay tuned on this because we anticipate this to generate a wealth of data. Now let's move on to other NIH-funded studies. You all likely recall learning about the Framingham Study way back in med school. This was an NIH-funded study through the National Heart, Lung, and Blood Institute. It was a longitudinal study designed to examine the risks or characteristics contributing to cardiovascular disease. It began in 1948, and the original cohort recruited over 5,000 men and women aged 30 to 62 in Framingham, Massachusetts. Subjects enrolled in the study underwent extensive physical examinations as well as lifestyle interviews. Participants returned to the study every two to six years where detailed medical histories, physical exams, and laboratory tests have been collected. The study ultimately extended to include offspring as well as to collect data for risk factors for other conditions such as dementia. The incredible results from this study are that over 14,000 people from three generations have been studied, the original participants, their children, and now grandchildren. While some of these results seem obvious to us now, it was this study that found that high blood pressure and cholesterol were major risk factors for cardiovascular disease. The study has produced approximately 3,000 articles in leading medical journals, and the data collected from this longitudinal study is available for researchers to continue to spur new scientific discoveries. Eventually, researchers recognized the need to reflect Framingham's more diverse communities, and in 1994 enrolled the first OMNI cohort of 507 men and women to include African-American, Hispanic, Asian, Indian, Pacific Islander, and Native American individuals. In 2003, a second group of OMNI participants were enrolled. If you have any study ideas that may be eligible to use the data from this study, you can go through the Framingham Heart Study website or contact the program officer at NHLBI. Both of these are readily available on the internet and publicly, so easily searchable. The Nurses' Health Study is another NIH-funded study with continued support that was established by Dr. Frank Spitzer in 1976. The primary aim was to investigate potential long-term consequences of oral contraceptives. The investigators enrolled over 120,000 married registered nurses aged 30 to 55, and it remains one of the largest and longest-running studies on women's health. The study boasts that they have a continued 90% response rate of the original cohort after accounting for deaths. So while the original focus was contraceptive methods, smoking, cancer, and heart disease, the study has since expanded and evaluates vital information about lifestyle factors, behaviors, personal characteristics, and more than 30 diseases. And interestingly, at the time of the design, nurses were selected as the study population because of their knowledge about health and their ability to provide complete and accurate information regarding various diseases. The investigators anticipated and actually found that nurses were able to respond with a high degree of accuracy to brief technically worded questionnaires and were relatively easy to follow over time. So possibly because of their nursing backgrounds, they were thought to be more motivated to participate in a long-term study. Additionally, the population was limited to married women at that time due to the sensitivity of questions about contraceptive use in the 70s. Every two to four years, subjects continue to receive follow-up questionnaires regarding topics such as smoking, hormone use, diet, and nutrition. A food frequency questionnaire was added in 1980 as well as a quality of life supplement in 1992. Numerous supplemental questionnaires have also been sent to selected participants for additional data regarding specific research questions. The impressive thing about the nurses' health study is that not only did it include questionnaires, but they also gathered other information such as minerals from the soil where the food was grown. 63,000 nurses submitted toenail samples. Blood samples were collected from nearly 33,000 to identify potential biomarkers such as hormone levels and genetic markers. Second, blood and urine samples were also collected from greater than 18,000 subjects, 18,000 of the same participants. These samples are stored and used to study relationships between various biologic markers and disease risk. DNA has also been collected from cheek cells from an additional 33,000 participants. So this study offers a variety of data that can be utilized. And given the long-term nature of this study, extensions were named two and three. And if you're interested in reviewing or even using this data, investigators are encouraged to complete a form on their website and email it to the address listed here. All these contacts, again, are easily searchable on the internet. All of this is publicly available. The National Health and Nutrition Examination Survey, or NHANES, was first conducted by the National Center for Health Statistics, or NCHS, of the Centers for Disease Control. This began as a clustered, multistage stratified probability sample of over 20,000 individuals ranging from one to 74 years old. The subjects were drawn from non-institutionalized civilian populations. A random subsample of over 14,000 examined adults aged 25 to 74 were also given supplemental questionnaires on their cardiovascular and respiratory histories. In 1981, the National Institute on Aging, or NIA, and NCHS began a follow-up of the original NHANES-1 cohort. NHLBI then added a Framingham model verification component to this study, with their endpoints being coronary heart disease death as coded from death certificates. Results of the NHLBI portion of the follow-up actually demonstrated major risk factors for coronary heart disease mortality. In 1986, the total surviving cohort of NHANES-1, which was approximately 12,500 at that time, was recontacted. NHLBI contributed to funding NHANES-3 and currently contributes to NHANES-4. NHANES-3 incorporated a longitudinal component where subjects have been followed over time for statistics, reexamination, specimen banking, and particularly oversampling of African-American and Hispanic populations. Additional questions and procedures have been undertaken on common heart, vascular, lung, and blood diseases, risk factors, and elements of medical care. The longitudinal component is very impressive. It's also indicated how representative this NHLBI population-based epidemiological studies were and the extent to which the findings were generalizable. So NHANES has studied numerous conditions, some of which are listed here, and specifically for us, the reproductive history and sexual behavior can be relevant. Importantly, NCHS offers downloadable public-use data files. Users can obtain access to datasets, documentation, and questionnaires from NCHS surveys and data collection systems. As with other public resources, users must comply with data use restrictions and ensure that the information is used solely for statistical analysis or reporting purposes, and the information can be obtained here through the CDC website as shown. So finally, one of our other institutions, the National Institute of Diabetes and Digestive Diseases and Kidney Diseases, or NIDDK, also has a central repository that may be relevant to your interests. This is what the website looks like. It, again, requires you to register to review and access the data, but again, it does provide free access to study data. So the Urinary Incontinence Treatment Network may be something some of you have heard about. NIDDK established the UITN in 2000 as a multidisciplinary, multi-institutional network which has been completed. Many of our investigators were part of that. The goal was to investigate treatments for urinary incontinence in women. Nine academic sites and a data coordinating center were involved, and this network was definitely multidisciplinary. It was composed of urologists, urogynecologists, geriatricians, behavioral psychologists, physical therapists, nurses, epidemiologists, social scientists, and of course, statisticians. The NIDDK repository houses studies from the UITN. Obviously, due to the interest of time, I won't go into these in as much detail as the PFDN studies, but we will review a few of them. The SISTER trial compared birch copal suspension to autologous rectus fascial sling procedures for the treatment of stress incontinence. There is the TOMAS trial, which examined the efficacy of a retropubic midurethral mesh sling versus a trans-operator midurethral sling. And the VALUE trial, which examined whether there were differences in outcomes of women who underwent only a basic office evaluation versus those who underwent urodynamic testing in addition to the office evaluation prior to the treatment of stress incontinence. And other network and non-network urinary trials are also found on this NIDDK repository. So, as you can see, there's an abundance of data available to you from many, many studies. I did harbor on the NIH-funded ones because obviously those are the ones that have easy access to me. We clearly did not cover everything, but hopefully you have a better understanding of what could be out there. There are validated questionnaires, POPQ exams, urodynamic results, voiding trial results, survey questionnaires. And you can use all of these to answer questions that you may have about correlations, risk factors, or other associations. I think this data is excellent for fellow projects because of the strict nature in which these studies were conducted. The data is reliable. And most importantly, somebody else has already done the hard work for you, so you just need a question to analyze. Most importantly, NICHD, the federal government, wants this data to be used because like we were talking about earlier, it's the best kind of use of the financial commitment. So I encourage you to think of ideas for secondary analyses that you can study using this data. So thank you again for your attention. It was as interesting of a talk as maybe some others are. If you have any questions after this, you can always feel free to reach out to me. The easiest email, I think, to remember, if you can spell my last name, is my NIH1, which is just firstname.lastname. But I welcome any questions. And I'll stop sharing my screen, I guess. So thank you. Dr. Maslund, just thank you so much for that presentation. Audience members, you can submit your questions through the Q&A. And it looks like we do have one question. One of the questions is, is there an opportunity that you can share your slides with all of the attendees? I think the webinar was recorded, correct? So that you'll have access to it. Correct. But yes, if there's anything specific, I'm happy to share it with anybody. Perfect. Sounds good. Anybody have any other questions? I don't see any other questions in the Q&A. I think people fell asleep. No, it was very, very interesting. Thank you so much, ma'am. I appreciate all the overview for the data. It's quite a lot of work, definitely, that has been put in through the years. Okay. If we don't have any other questions, I just want to, on behalf of AUGS, I'd like to thank Dr. Maslund-Dews for the presentation and everyone for joining us today. And for the full list of upcoming webinars, please visit the AUGS website to sign up. Thank you, guys. And I definitely encourage you to talk to, for those of you who are at sites of big research, it's a little bit easier for those of you who don't necessarily have the same resources. You can always reach out to me or any of the investigators. I know the PFDN investigators are all quite generous with their time and expertise, but I don't want to volunteer them. So you're welcome to reach out to me. But I think that there is a wealth of data out there that can be easily used. And if you need ideas, sometimes it helps to just see what other ancillary studies were done off of the primary PFDN studies, just to maybe trigger your thoughts. But please use the data, because we've already paid for it and done the hard work. Anyways, thank you. Thank you so much, ma'am.

Dr. Donna Maslamdoust

research regulation

data sharing policies

historical background

NIH-funded studies

Pelvic Floor Disorders Network

National Health and Nutrition Examination Survey

accessing data