ClinicalTrials: Results Reporting, Unique Evidence, and the Role of the Medical Librarian

1. ClinicalTrials.gov: Results Reporting, Unique Evidence, and the Role of the Medical Librarian National Network of Libraries of MedicineSoutheastern Atlantic Region Liz Waltman / ewaltman@hshsl.umaryland.edu

2. National Network of Libraries of Medicine • Trainings • Funding • Educational materials • Community outreach Find your regional office! https://nnlm.gov/regions

3. Course Objectives:

4. Poll: What is your experience using ClinicalTrials.gov? I’m an expert! I use it occasionally! I’ve never used it! I use it a lot, but want more tips and tricks.

5. What is a Clinical Study? A research study using human subjects to evaluate biomedical or health-related outcomes Clinical Study Definition(http://clinicaltrials.gov/ct2/about-studies/glossary)

6. Two Types of Clinical Studies: Study type definition(http://clinicaltrials.gov/ct2/about-studies/glossary)

7. Clinical Trial Process Tse T, Zarin DA, Williams RJ, Ide NC. The Role and Importance of Clinical Trial Registries and Results Databases. In: Gallin JI, Ognibene FP, editors. Principles and Practice of Clinical Research. London: Academic Press; c2012. p. 171-181.

8. Clinicaltrials.gov homepage

9. Clinicaltrials.gov map feature

10. Types of Registered Trials Slide courtesy of Kristina Elliot (ClinicalTrials.gov)

11. Who Uses ClinicalTrials.gov?

12. Public Benefits of Access to Clinical Trial Information • Meet ethical obligation to human subjects • Inform future research and research funding decisions • Mitigate information bias (e.g., non-publication) • Evaluate research integrity (e.g., adherence to protocol) • Prevent duplication of trials of unsafe or ineffective interventions • Provide access to data to support evidence-based medicine • Enhance patient access to enrollment in clinical trials All contribute to increased public trust in clinical research!

13. Patients and Families • ClinicalTrials.gov offers a reliable and generally comprehensive list of ongoing trials that people might consider enrolling in • Gives patients a centralized place to search by condition, location, and other trial characteristics • “Access to more information about clinical trials is good for patients, the public and science,” NIH Director Francis S. Collins, M.D., Ph.D. 

14. Patients lose sight after stem cells are injected into their eyes: NYTimes article URL for data source

15. Clinical Researchers ClinicalTrials.gov: • Is a place to find information on ongoing and completed clinical trials that may not be published • Is a place to find unique evidence for systematic reviews • Enables analyzing of data in the registry to reveal trends in the clinical research enterprise • Provides available evidence relevant to a specific clinical topic

16. How soon after completion date do summary results for trials need to be submitted to the registry?

17. Librarians • Can inform the clinical research community about the significance of complying with results reporting requirements • Can assist health professionals and researchers in learning about the results database in ClinicalTrials.gov to find results information that may not be published • Can direct patients to ClinicalTrials.gov so they can find information about trials to discuss with their health provider • Can assist patients and their families to find studies for their own use

18. Questions to Ask • What is being studied? • Why do researchers believe the intervention being tested might be effective? Has it been tested before? • What are the possible interventions that I might receive during the trial? • How will it be determined which interventions I receive (for example, by chance)? • Who will know which intervention I receive during the trial? Will I know? • How do the possible risks, side effects, and benefits of this trial compare with those of my current treatment? • What will I have to do? • What tests and procedures are involved? • How often will I have to visit the hospital or clinic? • Will hospitalization be required? • How long will the study last? • Who will pay for my participation? • Will I be reimbursed for other expenses? • What type of long-term follow-up care is part of this trial? • If I benefit from the intervention, will I be allowed to continue receiving it after the trial ends? • Will results of the study be provided to me? • Who will oversee my medical care while I am participating in the trial? • What are my options if I am injured during the study? URL for source

19. Increased Requirements for Registration and Results Reporting • Selective publication makes it difficult to determine the true value of a treatment • Comparisons of published drug trials with unpublished trials or other available data have shown that the benefits of a number of drugs have been much overrated and the harms much underrated • As a result, FDAAA law and ICMJE policy require clinical trial registration and results reporting to increase access to clinical trial data

20. Final Rule “The new rule expands the legal requirements for submitting registration and results information for clinical trials involving U.S. Food and Drug Administration-regulated drug, biological and device products. At the same time, the National Institutes of Health has issued a complementary policy for registering and submitting summary results information to ClinicalTrials.gov for all NIH-funded trials, including those not subject to the final rule.”  NIH press release (https://www.nih.gov/news-events/news-releases/hhs-takes-steps-provide-more-information-about-clinical-trials-public)

21. ICMJE and FDAAA charts ClinicalTrials.gov registration results (https://clinicaltrials.gov/ct2/resources/trends)

22. Librarians’ Role

23. Registration Requirements Registration requirements (http://clinicaltrials.gov/ct2/manage-recs/background) *Section 801 of the Food and Drug Administration Amendments Act (FDAAA 801) **International Committee of Medical Journal Editors (ICMJE)

24. Advocating to Clinical Researchers

25. Challenges in Submitting Results • Lack of awareness of results submission requirements • Results submission must be completed by someone familiar with the study and data, and experienced with ClinicalTrials.gov tabular format Tse T, Zarin DA, Williams RJ, Ide NC. The Role and Importance of Clinical Trial Registries and Results Databases. In: Gallin JI, Ognibene FP, editors. Principles and Practice of Clinical Research. London: Academic Press; c2012. p. 171-181.

26. Contact ClinicalTrials.gov! If you or a researcher are submitting results for the first time, contact ClinicalTrials.gov!Their well-trained staff can provide 1-on-1 assistance with any results submission.Email: register@clinicaltrials.gov

27. Clinicaltrials.gov homepage ClinicalTrials.gov (https://clinicaltrials.gov/)

28. Exercise 1: Find a currently recruiting study in your state for seniors with emphysema ClinicalTrials.gov (https://clinicaltrials.gov/)

29. Exercise 2: Search for recruiting studies looking for sickle cell patients, using a gene therapy intervention ClinicalTrials.gov (https://clinicaltrials.gov/)

30. More about study results- • The study results will be displayed in a tabular format that includes the following information: • Participant Flow • Baseline Characteristics • Outcome Measures and Statistical Analyses • Adverse Events • Limitations and Caveats • Administrative information • ***If no results have been posted on ClinicalTrials.gov, the results tab is labeled "No Study Results Posted. " *** How to find study results (https://clinicaltrials.gov/ct2/help/how-find/find-study-results)

31. Additional ways to find study results: Searching PubMed for results of studies: • In PubMed, use clinicaltrials.gov[si] • ~75,000+ published articles

32. Exercise 3: Find study results for a completed study on skin cancer, squamous cell with a drug intervention ClinicalTrials.gov (https://clinicaltrials.gov/)

33. Exercise 4: Find an article in PubMed with published study results on a randomized control trial relating to Alzheimer’s (Hint: remember the filter!) ClinicalTrials.gov (https://clinicaltrials.gov/)

34. Recap • Clinical trials are important for research discoveries • ClinicalTrials.gov is a valuable, free resource for patients, their families, and researchers • Complying with federal requirements for registering studies is necessary for the continuation of studies and for the betterment of medical research • Librarians are important advocates for ClinicalTrials.gov

35. Thank You! Liz Waltman / ewaltman@hshsl.umaryland.edu Developed resources reported in this presentation are supported by the National Library of Medicine (NLM), National Institutes of Health (NIH) under cooperative agreement number UG4LM012340 with the University of Maryland, Baltimore.  The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.