Order Code RL32832
Clinical Trials Reporting and Publication
Updated April 27, 2007
Erin D. Williams
Specialist in Bioethical Policy
Domestic Social Policy Division

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Clinical Trials Reporting and Publication
Summary
The central issue before Congress with respect to clinical trials reporting and
publication is how to balance the potential beneficial public health effects of
requiring that clinical trials data be made public with the burdens that such
requirements may place on companies and their innovation. Clinical trials, which
are conducted regularly to test the effects of new pharmaceuticals and medical
devices, cost a significant amount of money, and by their nature may present some
risk to the people who participate in them. Manufacturers as well as medical journal
editors have been reluctant to publish clinical trial data indicating that products in
development are harmful or ineffective. The availability of such information might
save a duplication of effort and studies that harm or fail to help patients.
While current federal regulations require the publication of some clinical trials
data, and some private entities have taken steps to encourage publication, there is no
requirement that the public have access to all standardized clinical trials data — be
it notice of trial launch or research results through a centralized system such as a
registry. Food and Drug Administration (FDA) regulations require sponsors of trials
that test the effectiveness of new drugs for serious or life-threatening conditions to
register with the Department of Health and Human Services (HHS) at
[http://clinicaltrials.gov/], although not all such trials are listed there. Clinical trial
data from National Institutes of Health (NIH)-funded research may be made public
through a Freedom of Information Act request only if the findings were used by the
federal government in developing an agency action that has the force and effect of
law. The International Committee of Medical Journal Editors (ICMJE) requires, for
publication of clinical trial results, that a sponsor have posted its trial in a public
registry before enrolling patients. A voluntary registry of recent controlled trials
results was created in October 2004 by the Pharmaceutical Research and
Manufacturers of America (PhRMA).
Proposals for public access to all or most clinical trial data raise a variety of
issues. These relate to the goals of providing public access, the appropriateness of
the information and its presentation for the audience, the timing of a trial’s inclusion,
whether reporting should be mandatory, potential conflicts of interest, and whether
medical device trials should be included.
Eight relevant bills have been introduced during the 110th Congress. One, the
Fair Access to Clinical Trials (FACT) Act (S. 467), would require the registration of
clinical trials, some of which must currently be registered at [http://clinicaltrials.gov],
and the subsequent posting of their results. The act would also make public certain
information about FDA’s non-approval actions, which is currently not required to be
released. Seven other bills, the Food and Drug Administration Revitalization Act (S.
1082), the Enhancing Drug Safety and Innovation Act of 2007 (S. 484 / H.R. 1561),
the Food and Drug Administration Safety Act of 2007 (S. 468 / H.R. 788), and the
Pediatric Medical Device Safety and Improvement act of 2007 (S. 830 / H.R. 1494)
also contain provisions about clinical trials reporting and publication.
This report will be updated on a regular basis.

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Contents
Introduction: Current Federal Regulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Clinical trials are the gold standard . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Federal regulations require the publication of
certain clinical trial information and encourage
the disclosure of some results . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Non-Federal Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
World Health Organization (WHO) promotes
trial registry standards, portal, and registration
of all clinical trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
The International Committee of Medical Journal Editors
(ICMJE) Clinical Trial Publication Policy
requires registration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
American Medical Association (AMA) recommends
a comprehensive clinical trials registry . . . . . . . . . . . . . . . . . . . . . 7
The Association of American Medical Colleges
(AAMC) develops principles for clinical trials reporting . . . . . . . 7
The Institute of Medicine (IOM) supports
mandatory trial registration and results reporting . . . . . . . . . . . . . 7
The pharmaceutical industry favors limited,
voluntary clinical trial registration and reporting . . . . . . . . . . . . . . 8
Legislation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Registry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Results Database . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Goals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Appropriateness/Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Timing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Voluntary or Mandatory/Penalties . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Conflicts of Interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Appendix A. World Health Organization,
International Clinical Trials Registry Platform,
Registration Data Set (Version 1.0) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
List of Tables
Table 1. Comparison of Proposals for Clinical Trials Reporting
and Publication in the 110th Congress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

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Clinical Trials Reporting and Publication
Introduction: Current Federal Regulations
In 2004, Congress and others raised questions about the safety and effectiveness
of several FDA-approved biomedical products on the market. These included certain
antidepressants, Merck’s pain relief drug, Vioxx, Boston Scientific’s cardiac stents,
and other drugs and medical devices. Discussion about ways to help ensure safety
and effectiveness of biomedical products focused primarily on two questions:
whether data from all clinical trials should be made publicly available, and whether
FDA’s processes for product approval and post-market surveillance and study are
adequate. This report focuses on the first of these questions.1
The central issue before Congress with respect to clinical trials reporting and
publication is how to balance the potential beneficial public health effects of
requiring that clinical trials data be made public with the burdens that such
requirements may place on companies and their innovation. On one hand, companies
may lose a competitive advantage if their competitors are alerted to their clinical
trials activities and failures. On the other hand, the public may be harmed if a
particular type of clinical trial is repeated — particularly if an earlier trial
demonstrated that a product was ineffective or harmful. In addition, if clinical trial
data are to be made public, the timing and contents of the disclosure may prove to be
pivotal, both with respect to competitive innovation and public safety.
Clinical trials reporting can mean public access to results after a trial’s
conclusion, to a proposed plan before a trial is begun, or both. There is no
centralized system for either type of reporting; thus, different trials may have the
same title, one trial may be reported in several places under different titles, and many
trials are never reported. Researchers have traditionally reported pre- and post-
market trial results in peer-reviewed medical journals, which have historically tended
to favor publication of clinical trials demonstrating successful intervention; the
results of negative or inconclusive trials often go unpublished.2 Other venues for the
dissemination of research results are industry, government, or university press
releases and presentations at medical conferences. Researchers — who may be
affiliated with a product’s manufacturer, a university, the government, or an
association established to find better treatments for a particular disease — may have
various motives for publishing or not publishing results. Some observers have
1 For further information about whether FDA’s processes for product approval and
post-market surveillance and study are adequate, see CRS Report RL32797, Drug Safety and
Effectiveness: Issues and Action Options After FDA Approval, by Susan Thaul.
2 “Pressure Mounts for Clinical Trial Registry,” Medicine & Health, vol. 58, no. 24 (June
21, 2004), pp. 2-3.

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expressed concern that a lack of transparency, particularly for negative data, could
adversely affect medical decision-making.3
The lack of transparency may be amplified in part by sponsors’ contractual
requirements of their researchers. This concern was raised by two May 2005 medical
journal articles, suggesting that contractual “gag” clauses might prohibit clinical trial
investigators from examining data independently or submitting a manuscript for
publication without first obtaining the consent of trial sponsors. According to one
of the articles, sponsors with a financial interest in the outcomes of clinical research
could thus suppress negative results and interfere with the publication of unfavorable
data on safety.4 The other article, which described results from a survey of medical
school research administrators responsible for negotiating clinical trial agreements
with industry sponsors, reported that industry provides approximately 70% of
funding for clinical drug trials in the United States.5 The survey results suggested
that 85% of the administrators’ offices would not approve provisions that gave
industry sponsors the authority to revise manuscripts or to decide whether results
should be published. Administrators’ responses varied regarding whether contracts
could contain provisions allowing sponsors to insert their own statistical analyses in
manuscripts, draft manuscripts, or prohibit investigators from sharing data with their
parties after the trial’s conclusion.
In order to fully understand the debate surrounding clinical trials reporting and
publication, a basic understanding of clinical trials themselves and of the current
federal requirements — both of which are presented below — is essential. The slate
of issues that frequently arise during discussions of clinical trials reporting and
publication, all of which are addressed below in the “Issues” section of this report,
include questions related to the goals of publication, the materials’ appropriateness
and presentation, the timing the disclosures, whether disclosure should be voluntary
or mandatory with penalties, overcoming potential conflicts of interest, and whether
medical devices should be included in reporting requirements.
Clinical trials are the gold standard. Clinical trials, which are the gold
standard for assessing drug and device safety and effectiveness both before and after
they are marketed in the United States, are scientific studies that systematically test
interventions on human beings. They may include behavioral studies or other
biomedical investigations, such as those that test drugs and medical devices. As
described by FDA, clinical trials are generally conducted in four phases following
successful animal testing.6 Phase I trials study a new drug or device in a small group
3 Robert Steinbrook, “Public Registration of Clinical Trials,” JAMA, vol. 351, no. 4 (July
22, 2004), p. 315.
4 Robert Steinbrook, “Gag Clauses in Clinical-Trial Agreements,” New England Journal of
Medicine, vol. 352, no. 21 (May 26, 2005), p. 2160.
5 Michelle Mello, et al., “Academic Medical Centers’ Standards for Clinical-Trial
Agreements with Industry,” New England Journal of Medicine, vol. 352, no. 21 (May 26,
2005), p. 2202.
6 For further information on the role of federal agencies in evaluating biomedical products,
(continued...)

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of people (20-80) to evaluate its safety, determine a dosage range for drugs, and
identify gross side effects. Phase II trials study the product in a larger group of
people (100-300) to see whether it is effective for a specific purpose and to further
evaluate its safety. Phase III trials investigate the product in a large group of people
(1,000-3,000), to confirm the product’s effectiveness, monitor side effects, and
collect information that will allow the drug, treatment or device to be used safely.
Phase IV trials are usually large-scale studies, conducted after the FDA approves a
product for marketing in order to demonstrate effectiveness in a broader clinical
context and to watch for rare side effects that may not be identified until significant
numbers of people have used the product.
Federal regulations require the publication of certain clinical trial
information and encourage the disclosure of some results. The federal
government has historically regulated certain aspects of some clinical trials by
attaching conditions to those conducted with federal research funds, and/or by
creating requirements that must be met before a drug or device can be marketed in
the United States. Most federal funding occurs through the Department of Health
and Human Services’ (HHS) National Institutes of Health (NIH). According to
NIH’s regulations issued pursuant to a provision in the Omnibus Consolidated and
Emergency Supplemental Appropriations Act, 1999 (P.L. 105-277), research data
relating to published research findings produced under an award that were used by
the federal government in developing an agency action that has the force and effect
of law — a limited number of research results if any — must be released if a
Freedom of Information Act request is made.7
Beginning in May 2005, the NIH has requested that investigators with
manuscripts that are accepted for publication, and that are the result of research
supported in whole or in part with direct costs from NIH, submit them voluntarily to
the National Library of Medicine’s (NLM’s) PubMed Central.8 (The NLM, which
is located on the NIH campus in Bethesda, Maryland, is the world’s largest medical
library.) This effort would enables free access to results published elsewhere and
would not facilitate access to previously undisclosed results. The NIH announcement
was preceded by a July 2004 House committee recommendation that NIH provide
free public access to the complete text of articles and supplemental materials
generated by NIH-funded research.9
6 (...continued)
see CRS Report RS21962, From Bench to Bedside: The Role of Health and Human Services
(HHS) Agencies in the Evaluation of New Medical Products, by Michele Schoonmaker.
7 Uniform Administrative Requirements for Grants and Agreements With Institutions of
Higher Education, Hospitals, and Other Non-Profit Organizations; Final Rule (Office of
Budget Management, Circular A 110), Federal Register, Vol. 65, No. 52, Page 14406
(March 16, 2000), at [http://grants2.nih.gov/grants/policy/a110_fed_reg_20000316.pdf].
8 National Institutes of Health, “Policy on Enhancing Public Access to Archived
Publications Resulting from NIH-Funded Research,” NOT-OD-05-022, February 2, 2005,
at [http://grants2.nih.gov/grants/guide/notice-files/NOT-OD-05-022.html].
9 U.S. Congress, House Committee on Appropriations, Departments of Labor, Health and
Human Services, and Education and Related Agencies Appropriations Bill, 2005, report to
(continued...)

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Both pre-market approval and post-market monitoring of medical drugs and
devices marketed in the U.S. are the responsibility of HHS’s FDA. Each FDA center
that reviews and approves biomedical products for human use — the Center for Drug
Evaluation and Research, the Center for Devices and Radiological Health, and the
Center for Biologics Evaluation and Research — posts summaries of safety and
effectiveness data from clinical trials that support approved applications for new
products, or new uses of approved products; FDA does not otherwise post clinical
trials data.
The FDA Modernization Act of 1997 (FDAMA, P.L. 105-115, Section 113)
required the Secretary of HHS to establish a clinical trials registry, intending the
availability of information to increase the access of individuals to cutting-edge
medical care available only through research protocols. Sponsors of trials testing the
effectiveness of life-threatening disease or condition treatments (drugs, but not
devices) that are being conducted to obtain FDA approval for marketing,10 under an
expanded use protocol11 of an investigational new drug application to FDA, or on
Group C12 cancer drugs are required to register. In addition, any trial (drug, device,
or other) that has been approved by a human subject review board (or equivalent) and
conforms to the regulations of the appropriate national or international health
authority may also be included.
In response to FDAMA, the NLM established a clinical trials registry and made
it available to the public in 2000 [http://clinicaltrials.gov]. It was later reported that
an FDA analysis found that in 2002 only 48% of trials of cancer drugs had been
registered, and a preliminary review indicated the listing rate for drugs for some other
serious diseases is in the single digits. Some companies had reportedly listed no
studies; some trials were listed without identifying the sponsoring company or the
drug being tested.13 In March 2002, FDA issued a guidance document, instructing
9 (...continued)
accompany H.R. 5006, 108th Cong., 2nd sess., H.Rept. 108-636 (Washington, GPO, 2004).
10 Pursuant to 21 U.S.C. § 355(i).
11 An expanded use protocol is one that allows for widespread patient access to an
investigational new drug not yet approved for marketing, when the drug has shown promise
for treating a serious or life-threatening condition, there is no comparable or satisfactory
alternative therapy, and the sponsor is actively pursuing permission to market the drug (21
U.S.C. § 360bbb(c)).
12 Group C “was established by agreement between FDA and the National Cancer Institute
(NCI). The Group C program is a means for the distribution of investigational agents to
oncologists for the treatment of cancer under protocols outside the controlled clinical trial.
Group C drugs are generally Phase 3 study drugs that have shown evidence of relative and
reproducible efficacy in a specific tumor type. They can generally be administered by
properly trained physicians without the need for specialized supportive care facilities.
Group C drugs are distributed only by the National Institutes of Health under NCI
protocols.” Information Sheets: Guidance for Institutional Review Boards and Clinical
Investigators,1998 Update, Drugs and Biologics, FDA, at [http://www.fda.gov/oc/ohrt/irbs/
drugsbiologics.html].
13 Shankar Vedantam, “Drugmakers Prefer Silence on Test Data,” Washington Post, July 6,
(continued...)

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industry how and when to participate in the registry [http://www.fda.gov/cder/
guidance/4856fnl.htm].
A 2005 survey conducted by FDA’s Office of Special Health Issues indicated
that 67% of companies required to register their trials had done so.14 The 2005 survey
results were not comparable to those of 2002 due to methodological differences. It
was reported that FDA did not plan to continue to monitor whether companies
registered beyond 2006.15
In a July 2004 announcement unrelated to [http://clinicaltrials.gov/], the FDA
announced that clinical trial sponsors could use a standard format, the Study Data
Tabulation Model (SDTM) developed by the nonprofit organization Clinical Data
Interchange Standards Consortium (CDISC), to submit clinical trials data to the
agency [http://www.cdisc.org/index.html]. While the data would not necessarily be
made public, according to the FDA, providing a consistent framework and format for
clinical trial information is expected to enhance data integration opportunities and
thereby reduce data management barriers for sharing the latest clinical trial data.16
Non-Federal Activities
A number of national and international groups recommended that clinical trial
reporting be centralized, standardized, and/or include both positive and negative
results, and have taken steps toward that goal.
World Health Organization (WHO) promotes trial registry standards,
portal, and registration of all clinical trials. In May 2006, the WHO, the
United Nations specialized agency for health which supports and funds much of the
international research on marginalized populations, began urging research institutions
and companies to register all medical studies that test treatments on human beings,
including the earliest studies, whether they involve patients or healthy volunteers.17
This dovetails with another WHO initiative: the International Clinical Trials
Registry Platform (ICTRP), which aims to standardize the way information on
medical studies is made available to the public. As a part of the ICTRP, WHO has
13 (...continued)
2004, p. A 1.
14 “FDAMA Section 113: Status Report on Implementation,” FDA Office of Special Health
Issues, August 2005, at [http://www.fda.gov/oashi/clinicaltrials/section113/113report/
default.htm], visited January 17, 2007.
15 “FDA to Stop Tracking Industry Compliance With Clinical Trial Registry,” Inside
Washington Publishers, September 26, 2006.
16 “FDA Announces Standard Format That Drug Sponsors Can Use to Submit Human Drug
Clinical Trial Data,” FDA News, July 21, 2004, at [http://www.fda.gov/bbs/topics/
news/2004/NEW01095.html].
17 “The World Health Organization announces new standards for registration of all human
medical research,” World Health Organization website, May 19, 2006, [http://www.who.
int/mediacentre/news/releases/2006/pr25/en/index.html], visited January 18, 2007.

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recommended that 20 key details — such as title, funding source, research ethics
review, and outcome measures — be disclosed at the time studies are begun, that a
Universal Trial Reference Number be assigned to each trial, and that minimum
standards for the reporting of trial results be defined. (See Appendix A for a
complete list of key details.) As the ICTRP progresses, WHO plans to launch a
one-stop Search Portal for searching compatible registries worldwide.18
Some organizations have voiced opposition to the WHO efforts. The
Pharmaceutical Research and Manufacturers of America (PhRMA) has reportedly
opposed publicizing information early in the clinical trial, arguing that disclosing
early research data does little to help doctors and patients, and may impede
innovation by alerting competitors to companies’ activities.19 For similar reasons, the
Advanced Medical Device Medical Technology Association (AdvaMed) has
reportedly attempted unsuccessfully to allow device firms to delay disclosure of some
required data elements.20 AdvaMed argued that the issue was more pronounced for
device than drug manufacturers because device development process is iterative,
involving improvements over a period of time.
Since April 2004, all clinical trials approved by the WHO ethics review board
have been required to be registered at their outset and assigned a unique identification
number.21 A London-based group of biomedical publishing companies agreed to
maintain a no-charge, online register of these numbered trials at
[http://www.controlled-trials.com] to identify and track them throughout their life
cycle. The system was designed to avoid the problem of publication bias by posting
information on trial starts and their results.
The International Committee of Medical Journal Editors (ICMJE)
Clinical Trial Publication Policy requires registration. The ICMJE consists
of the editors of 12 major journals, including the New England Journal of Medicine,
The Lancet, and the Journal of the American Medical Association. In order for a
sponsor to have its clinical trial results published in one of the ICMJE journals, the
ICMJE requires it to have posted its trial in a public registry before enrolling
patients.22 The policy applies to any trial that started recruiting human subjects on
or after July 1, 2005. The ICMJE did not advocate any particular registry, but cited
18 “International Clinical Trials Registry Platform” World Health Organization website, May
19, 2006, [http://www.who.int/ictrp/en/], visited January 18, 2007.
19 “PhRMA Opposes UN Plan for Trial Data Disclosure,” Inside Washington Publishers,
May 30, 2006.
20 “AdvaMed, WHO at Odds Over Global Trial Registry Standards,” Inside Washington
Publishers, July 19, 2006.
21 Gerd Antes, “Registering clinical trials is necessary for ethical, scientific and economic
reasons,” Bulletin of the World Health Organization, May 2004, vol 82, no. 5., at
[http://www.who.int/bulletin/volumes/82/5/en/321.pdf], visited January 18, 2007.
22 Catherine De Angelis et al., “Clinical Trial Registration: A Statement from the
International Committee of Medical Journal Editors,” New England Journal of Medicine,
vol. 351, no. 12 (September 16, 2004), p. 1250, at [http://content.nejm.org/cgi/content/full/
351/12/1250].

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[http://clinicaltrials.gov/] as the only database currently meeting its requirements. In
June 2005, the ICMJE specified the minimum set of data elements necessary for a
trial to be considered fully registered, adopting the WHO list of 20 items.23
American Medical Association (AMA) recommends a
comprehensive clinical trials registry. In an effort at dovetailing with the
ICMJE requirements, in December 2004, the AMA House of Delegates committed
the organization to take all appropriate action to protect the rights of physician
researchers to present, publish, and disseminate data from clinical trials.24 In June
2004, the AMA recommended that HHS create a comprehensive, centralized clinical
trials registry. The AMA further called on all institutional review boards to make
registration in this database a condition of their approval of the bioethical aspects of
clinical trials.25 Noting the AMA’s position, Senators Tim Johnson and Christopher
Dodd called for a national clinical drug trial registry in a July 8, 2004 letter to the
heads of NIH and FDA.26
The Association of American Medical Colleges (AAMC) develops
principles for clinical trials reporting. In January 2006, the AAMC Executive
Committee approved a set of principles designed to promote standards for analyzing
and reporting the results of sponsored clinical research.27 The principles include,
among other things, that researchers have an ethical obligation to make their results
public, that contracts with sponsors should require a good-faith effort to publish
results, and that trials should be fully registered according to ICMJE standards within
21 days of their outset either in [http://clinicaltrials.gov/] or elsewhere.
The Institute of Medicine (IOM) supports mandatory trial
registration and results reporting. The IOM, a National Academies institute,
conducted a workshop on developing a national clinical trials registry.28 Workshop
23 Catherine DeAngelis et al., “Is This Clinical Trial Fully Registered?: A Statement from
the International Committee of Medical Journal Editors,” New England Journal of
Medicine, vol. 352, no. 23 (June 9, 2005), p. 2436, and [http://www.icmje.org/
clin_trialup.htm].
24 American Medical Association, “610. Physicians and Clinical Trials,” December 2004
Resolutions, at [http://www.ama-assn.org/meetings/public/interim04/resolutions.pdf].
25 Joseph M. Heyman, “AMA Encouraged by Early Signs of Industry Support for National
Clinical Trials Registry,” American Medical Association, press release, June 18, 2004, at
[http://www.ama-assn.org/ama/pub/category/13909.html].
26 “Senators Call for National Registry of Clinical Drug Trials,” Senator Tim Johnson, press
release, July 8, 2004 [http://johnson.senate.gov/~johnson/releases/200407/2004708B20.
html].
27 Susan Ehringhaus and David Korn, “Principles for protecting Integrity in the Conduct and
Reporting of Clinical Trials,” Association ofAmerican Medical Colleges, January 6, 2007,
at [http://www.aamc.org/research/clinicaltrialsreporting/clinicaltrialsreporting.pdf], visited
January 18, 2007.
28 Committee on Clinical Trials, Institute of Medicine of the National Academies,
Developing a National Registry of Pharmacologic and Biologic Trials (Washington, DC:
(continued...)

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participants presented a range of views on the need for registries, registry content,
implementation issues, and next steps. A separate draft publication published by
IOM in 2006 recommended that Congress require industry drug sponsors to register
phase 2-4 clinical trials at [http://clinicaltrials.gov/], and that initial postings be
supplemented by a summary of safety and efficacy results.29
The pharmaceutical industry favors limited, voluntary clinical trial
registration and reporting. The pharmaceutical industry’s reaction to clinical
trials reporting has been mixed, although as litigation and FDA and congressional
interest have increased, some individual manufacturers and groups have volunteered
to make some of their clinical trials data public. How the industry defines the types
of trials to include (e.g., hypothesis-testing or late-phase only) could affect a
registry’s utility. Initially skeptical, PhRMA introduced its own clinical trials
database in October 2004 at [http://www.clinicalstudyresults.org]. Companies that
market drugs in the United States can voluntarily post the positive and negative
results of controlled trials (mainly Phase III and IV studies) completed after October
2002 on the PhRMA database. As of April 16, 2007, 60 companies had posted
results for 343 drugs. According to FDA, more than 10,000 drugs are approved for
marketing in the United States. In January 2005, PhRMA additionally called for its
members to voluntarily post all hypothesis-testing clinical trials on NLM’s registry,
clinicaltrials.gov.
In January 2005, an international pharmaceutical federation of which PhRMA
is a member, the International Federation of Pharmaceutical Manufacturers and
Associations (IFPMA), announced that its members would voluntarily disclose
summary results of all industry-sponsored clinical trials.30 Trial results would be
published in a standard, non-promotional summary that would include a description
of trial design and methodology, results of primary and secondary outcome measures
described in the protocol, and safety results. In October 2005, IFPMA announced
that it had launched a search portal of clinical trial registries and databases
worldwide.31
28 (...continued)
The National Academies Press, 2006), at [http://books.nap.edu/catalog/11561.html#toc],
visited January 18, 2007.
29 Committee on the Assessment of the US Drug Safety System, Institute of Medicine of the
National Academies, The Future of Drug Safety: Promoting and Protecting the Health of
the Public, Advance Copy, Tuesday September 26, 2006, (Washington, DC: National
Academies Press, 2006), at [http://books.nap.edu/books/0309103045/html], visited January
18, 2007.
30 The announcement was made jointly with PhRMA, the European Federation of
Pharmaceutical Industries and Associations (EFPIA), and the Japanese Pharmaceutical
Manufactures Association (JPMA). International Federation of Pharmaceutical
Manufacturers and Associations (IFPMA), “Global Industry Position On Disclosure of
Information About Clinical Trials,” IFPMA Press Release, January 6, 2005, at
[http://www.ifpma.org/News/NewsReleaseDetail.aspx?nID=2205].
31 IFPMA, “IFPMA Improves Biomedical Data Transparency with Launch of First
Worldwide Clinical Trials Portal,” IFPMA Press Release, September 21, 2005, at
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Legislation
A number of bills related to clinical trials reporting and publication have been
introduced in the 110th Congress. One bill is solely focused on clinical trials
registration and reporting: S. 467, the Fair Access to Clinical Trials (FACT) Act,
introduced by Senator Dodd. Similar legislation was introduced in the 109th
Congress by Senator Dodd (S. 470) and Representative Waxman (H.R. 3196), and
in the 108th Congress by Senator Dodd (S. 2933) and Representative Markey (H.R.
5252).
Seven other bills introduced in the 110th Congress have components relevant to
clinical trials reporting and publication. These bills have been primarily focused on
drug safety and FDA reform. The Food and Drug Administration Reauthorization
Act (S. 1082), introduced by Senator Kennedy, is composed of titles on the topics of
reauthorizing the Prescription Drug User Fee Act, promoting drug safety, and
encouraging the development of pediatric medical drugs and devices. One subtitle
of the drug safety provisions would create a clinical trial registry and a clinical trial
results database. The Enhancing Drug Safety and Innovation Act of 2007 (S. 484 and
H.R. 1561), introduced by Senator Enzi and Representative Waxman, is composed
of titles designed to address the following topics at FDA: risk evaluation and
mitigation strategies, the Reagan-Udall Institute for Applied Biomedical Research,
clinical trials, and conflicts of interest. The clinical trials title of each bill contains
provisions that would create a clinical trial registry and results database. Although
many provisions of S. 484 and H.R. 1561 are identical, those related to clinical trials
reporting and publication are different.
Two other pieces of legislation with provisions related to clinical trials reporting
and publication are the identical companion bills S. 468 and H.R. 788, the Food and
Drug Administration Safety Act of 2007, introduced by Senator Grassley and
Representative Tierney. The act would establish a Center for Postmarket Evaluation
and Research for Drugs and Biologics at FDA. It would enable the Center Director
to require certain pre- and post-market studies, and would require the HHS Secretary
to make information about those studies available to the public.
The remaining two bills with provisions related to clinical trials reporting and
publication are the pediatric Medical Device Safety and Improvement Act of 2007
(S. 830 / H.R. 1484) introduced by Senator Dodd and Representative Markey. The
bills would expand tracking of FDA pediatric device approvals, modify and tighten
the humanitarian device exemption (which waives user fees associated with the
FDA’s review of medical device applications), require the NIH Director to designate
a point of contact to assist those seeking funding for pediatric device development,
create demonstration grants for improving pediatric device availability, amend
regulations governing the office of pediatric therapeutics and the pediatric advisory
committee, and enable the Secretary to order certain postmarket studies as a
condition of approval of pediatric medical devices. The bills would also require the
HHS Secretary, acting through the FDA Commissioner, to establish a database of
31 (...continued)
[http://www.ifpma.org/clinicaltrials.html], visited April 27, 2007.

---

CRS-10
clinical trials on pediatric devices. The database would include trials conducted in
conjunction with the aforementioned postmarket studies, or with FDA premarket
device approval, clearance, or qualification as for the humanitarian device exemption.
Details of five proposals for clinical trials reporting and publication contained
in S. 468 / H.R. 788, S. 467, S. 1082, S. 484 and H.R. 1561 are discussed in the text
that follows, and compared with current law in Table 1. Due to the narrow scope of
the proposal for clinical trial publication contained in S. 830 / H.R. 1484, it is not
incorporated into the text or table. For purposes of this report, the repository of
clinical trial information submitted at the outset of the trial is referred to as a registry,
and the repository of the trial conclusions is referred to as a results database.
Registry. Current law: Only trials that meet all three of the following criteria
must be included in the registry, clinicaltrials.gov: (1) The trial is testing a drug; (2)
The trial is being conducted to obtain FDA approval for marketing, is conducted
pursuant to an expanded use protocol of investigational new drug application to
FDA, or is conducted on a Group C cancer drug; and (3) The trial tests treatments
of serious or life-threatening conditions. Other trials that have been approved by a
human subject review board (or equivalent) and conform to the regulations of the
appropriate national or international health authority may also be included.
Each of the legislative proposals would expand the scope of the current law,
which requires only the registration of certain drug trials, to include trials related to
biologics as well. All but S. 484 would also require the inclusion of medical device
trials. S. 467 would also allow for the results of other types of trials to be voluntarily
submitted. All but S. 467 would also expand the registry to include trials beyond
those for the treatment of life-threatening diseases or conditions.
Results Database. Current law: there is no requirement that the results of
clinical trials be made publically available, except those included as a portion of
what FDA publishes upon its approval of an application.
Most of the bills (all but S. 1082) would require public disclosure of study
results. S. 1082 would require the NIH Director to issue a report and HHS Secretary
to create a rule based on that report regarding the best way to make clinical study
results available to the public.
Issues
Issues surrounding the possibility of clinical trials reporting and publication
have focused on a range of topics. Those topics are discussed below, with an
accompanying analysis of the clinical trials reporting and publication provisions
contained in S. 467, S. 1082, S. 484, H.R. 1561, and S. 468 / H.R. 788.
Goals. Proponents of public access to clinical trials data cite the need to
provide information to members of the general public, health care workers, and
researchers, both to help inform treatment decisions and to help eliminate abuses.
Industry advocates have also cited the potential benefits of public awareness of the
resources necessary to get a drug approved, and the elimination of duplicated failed
efforts. PhRMA cites making clinical trial results for U.S.-marketed pharmaceuticals

---

CRS-11
more transparent, and providing information to practicing physicians and their
patients. Each of the legislative proposals aims to make information available and
understandable to members of the public.
Appropriateness/Presentation. Some have questioned whether
registration and publication of clinical trials and their results are the best mechanism
for ensuring patient safety, both because the language may be too technical for lay
audiences, and because numerous trials may need to be viewed together in order to
draw meaningful conclusions — an analysis that would be difficult for many doctors
as well. (A single clinical trial may generate thousands of pages of documentation.)
These questions have led some to focus on how information might be presented in
an audience-appropriate way. PhRMA’s registry contains a link to drug labels, a
bibliography, and a summary of results in a format developed by industry
consensus.32 All of the bills would contain information accessible to both the general
public and professionals. Two, S. 484 and H.R. 1561, have the additional specific
requirement that the results database contain both a technical and a nontechnical
summary report, which might meet the differing requirements of professionals and
lay persons.
Timing. Some have argued that only clinical study results are important to
judging effectiveness, so publication of a trial’s inception is not necessary. Others
have argued that some registration at inception is necessary to avoid abuse, and is
helpful for connecting potential subjects with various trials. FDAMA requires that
notice of a qualifying trial be submitted to [http://clinicaltrials.gov/] no later than 21
days after the trial is open for enrollment. PhRMA’s database only accepts results
from completed trials. S. 467 and S. 1082 would generally require registration within
21 days that a trial is opened for enrollment. S. 484 and H.R. 1561 would require
enrollment within 14 days after the first patient is enrolled. S. 467 / H.R. 788 would
require that information about the study be posted not less frequently than every 90
days. For results submissions, S. 467 and H.R. 1561 would require them to be
submitted within one year of the earlier of the trial’s actual or estimated completion
date. S. 484 would require results submissions not later than one year after the last
patient has his or her last medical visit, and S. 467 / H.R. 788 would require results
to be submitted upon completion of the study. All the bills except for S. 467 / H.R.
788 would allow for extensions for results submission in certain circumstances, such
as when publication in a peer-reviewed journal is pending. S. 467 / H.R. 788 may
also allow for such extensions by nature of the fact that the Director of the act-created
Center for Postmarket Evaluation and Research for Drugs and Biologics would
determine the studies completion date, and might therefore be capable of delaying the
date if presented with good cause.
Voluntary or Mandatory/Penalties. Concerns about the potential regulatory
burden on smaller drug and device manufacturers, as well as about the potential for
intellectual property problems, have led some to call for voluntary registration and
publication. The desire to protect public safety and to reduce abuse has led others to
back mandatory reporting. PhRMA’s registry is voluntary. The reporting proposed
32 Structure and Content of Clinical Study Reports; Guideline Approved by the International
Conference on Harmonization, July 1996, at [http://www.fda.gov/cder/guidance/iche3.pdf].

---

CRS-12
in all of the bills would be mandatory (with limited exceptions for trials not
conducted on drugs, devices, or biological products and those completed before the
bill’s enactment) and would carry penalties for noncompliance.
Conflicts of Interest. Some commentators have focused on the need for
public disclosure of financial and other arrangements between researchers and
sponsors in order to demonstrate potential conflicts of interest that may affect clinical
trial design, interpretation of data, and presentation of results. The PhRMA database
does not include information about funding relationships, though products there are
identifiable by company, which may also be the trial funding source. All of the bills
would require the disclosure of funding source(s), among other things.
Devices. Some have questioned whether information about clinical trials
related to medical devices should be included in the registry. The medical device
advocacy group, Avamed, points out that FDA regulation of devices is different from
its regulation of drugs. Devices are often approved based on analytical comparisons
to existing products rather than on the conduct of new clinical trials. Devices as
compared to drugs often tend to present a lower risk to patients, tend to be
manufactured by smaller companies, tend to have a short market life due to frequent,
incremental refinements rather than major breakthroughs, and tend to require more
financial incentives to test. PhRMA’s database contains only information related to
drug trials; those proposed in all of the bills except S. 468 / H.R. 788 would include
trials related to medical devices. S. 467 / H.R. 788 would require the HHS Secretary,
in consultation with the FDA Commissioner, the Director of the Center for
Postmarket Evaluation and Research for Drugs and Biologics, and the Director of the
Center for Devices and Radiological Health, to submit to Congress a report that
identifies gaps in the current process of postmarket surveillance of devices approved
under the Federal Food, Drug, and Cosmetic Act, includes recommendations on ways
to improve gaps in postmarket surveillance of devices, and identifies the changes in
authority needed to make those improvements.

---

CRS-13
Table 1. Comparison of Proposals for Clinical Trials Reporting and Publication in the 110th Congress
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
Title
Data bank of
FACT Act
Food and Drug
Food and Drug
Enhancing Drug
Food and Drug
information on clinical
Administration
Administration
Safety and
Administration
trials for drugs for
Revitalization Act Revitalization Act Innovation Act of
Safety Act of 2007
serious or
2007
life-threatening
diseases and conditions
Sponsor
Senator Dodd
Senator Kennedy
Senator Enzi
Representative
Senator Grassley,
Waxman
Representative
Tierney
Law Amended
(Existing law) PHSA
PHSA (42 U.S.C.
PHSA (42 U.S.C.
Subsection (i) of
Subsection (i) of
Chapter V of the
(42 U.S.C. § 282 (j))
282), as amended
282), as amended; section 402 of
section 402 of
FFDCA (21 USC
by Public Law
and Section 492
PHSA (42 USC
PHSA (42 USC
351, et seq.)
109-482; and
A(a) of the PHSA
282 as amended
282), as amended
Section 492 A(a)
by PL 109-482).
by PL 109-482.
of the PHSA
Registry and/or
Registry only
Both
Registry
Both
Both
Both, to the extent
Results
(clinicaltrials.gov);
expanded, and
that information to
Database
with sponsor consent,
includes links to
be made public is
Required
registry may also
certain results.
about ongoing
include information
Results database
studies and their
about the results of
to be created by
results.

---

CRS-14
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
registered trials,
HHS Secretary
including potential
rulemaking
toxicities or adverse
following
effects
recommendations
to be made in NIH
Director’s report
about best,
validated method
of making trial
results publically
available.
Product Trial
REGISTRY:
BOTH:
REGISTRY:
BOTH:
BOTH:
BOTH:
Types Included
Drugs
Drugs, biologics,
Drugs, devices,
Drugs, biologics,
Drugs, devices,
Drugs and
devices.
biologics
eventually
biologics
biologics.
Information about
possibly devices
other trials may be
voluntarily
submitted.
Public Access
REGISTRY:
BOTH:
REGISTRY:
BOTH:
BOTH:
BOTH:
Yes, via information
Yes, via
Yes, via Internet. Yes, via Internet.
Yes, via Internet.
Yes, via
systems, which are to
information
Internet posting
Internet posting
FOIA request
publication in the
include toll-free
systems, which are and FOIA request
and FOIA request
disclosures not
Federal Register
telephone
to include toll-free disclosures limited disclosures limited available for
and posting on an
communications
telephone
to terms of the act. to terms of the act. results for which
Internet website.

---

CRS-15
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
communications.
Secretary
Secretary
the principal
Provisions related
promulgates
promulgates
investigator is
to disclosure of
regulations that
regulations that
seeking
FDA reviews
notice of posting
notice of posting
publication.
supersede FOIA.
be part of
be part of
informed consent.
informed consent.
Location of
REGISTRY:
BOTH:
REGISTRY:
BOTH:
BOTH:
Not specified.
Databases
NLM at NIH is current Not specified, but
NLM at NIH
NIH.
NIH.
location
bill amends the
REGISTRY:
REGISTRY:
portion of the
Either supplants or Either supplants or
USC related to the
builds on
builds on
current registry,
clinicaltrials.gov,
clinicaltrials.gov,
which is located at
whichever is more whichever is more
NLM at NIH.
efficient.
efficient.
Links Between
REGISTRY:
Not specified,
REGISTRY:
REGISTRY:
BOTH:
None specified.
Registry,
Not specified; except
except that the
Entries link to
Entries link to
Corresponding
Results
that the activities of the Secretary shall
certain existing
results entries.
registry and
Database
data bank are to be
assign each
results.
results database
integrated and
clinical trial a
entries link to one
coordinated with
unique identifier
another.
related activities of
to be included in
other agencies of the
the registry and in
DHHS, and, to the
the database.
extent practicable,

---

CRS-16
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
coordinated with other
data banks containing
similar information.
Who Submits
REGISTRY:
BOTH:
REGISTRY:
BOTH:
BOTH:
BOTH:
Information
Sponsor
Responsible party
Responsible party
Responsible party
Responsible party
Sponsor
(RP): if such
(RP): sponsor; if
(RP): sponsor, or
(RP): primary
clinical trial is the
no sponsor exists-
principal
sponsor as defined
subject of an
grantee, contractor investigator if
by WHO, or
investigational
or awardee of
designated by
principal
new drug
federal funding; if sponsor
investigator (PI) if
application or an
designated by
designated by
application for an
sponsor, grantee,
sponsor and if PI
investigational
contractor or
is responsible for
device exemption awardee -
conducting the
— the sponsor; if
principal
trial, has access to
not — the person
investigator.
and control over
that provides the
data, has the right
largest share of
to publish trial
monetary support,
results, and has
but if that person
the responsibility
is federal or state
to meet the RP
agency — the
responsibilities.
principal
investigator; if the
main funder is a
nonprofit — the

---

CRS-17
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
nonprofit alone or
jointly with the
principal
investigator; if a
request is made to
the Secretary that
another person be
the RP, and that
person provides
monetary support
for the trial is
responsible for the
conduct of the trial
and will be
responsible for
submitting
required trial
information —
that person.

---

CRS-18
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
Who Receives
REGISTRY:
BOTH:
REGISTRY:
BOTH:
BOTH:
BOTH:
Information
HHS Secretary, acting
HHS Secretary,
Director of NIH
Director of NIH
Director of NIH
Director of FDA
through the NIH
acting through the
Center for
Director
NIH Director
Postmarket
Evaluation and
Research for
Drugs and
Biologics created
by Act (Center
Director)
Timing of
REGISTRY:
REGISTRY:
REGISTRY:
REGISTRY:
REGISTRY:
BOTH:
Submission
Not later than 21 days
-Initially: not
-Initially: not
-Initially: not
-Initially: not
-During the
after the approval of the later than 21 days
later than 21 days
later than14 days
later than14 days
study: not less
protocol
after the trial is
after the first
after first patient
after first patient
frequently than
opened for
patient is enrolled. is enrolled
is enrolled
every 90 days
enrollment.
-Change in
-Change in
-Updates: not less -Upon Study
RESULTS:
enrollment
Enrollment
than once every 6
Completion:
-Initially: implied status: not later
Status: not later
months
results to be
same date as for
than 30 days after
than 30 days after
-Change in
submitted upon
registry. (To the
change.
change
Enrollment
completion of
extent practicable, -Completion of
-Final
Status: not later
study.
the Secretary
trial: not later
Submission: Not
than 30 days after
Completion date
ensures that where than 30 days after
later than 30 days
change
determined by
the same
the last patient
after last enrolled
-Notice of trial
Center Director.
information is
enrolled in the
patient has last
completion: Not
required for the
clinical trial has
medical visit
later than 30 days
registry and the
completed his or
RESULTS:
after final
database (such as
her last medical
-Generally: Not
collection of data

---

CRS-19
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
initial information visit, whether the
later than 1 year
from subjects for
required for the
clinical trial
after last enrolled
primary and
database), a
conducted
patient has last
secondary
process exists to
according to the
medical visit
outcomes
allow the RP to
prespecified
(extensions
RESULTS:
make only one
protocol or plan
possible).
-Generally: Not
submission.
was terminated
-Changes in
later than 1 year
-Results: not later (extensions
regulatory status: after earlier of
than 1 year than
possible).
within 30 days
estimated or actual
the earlier of the
after change
completion date
trials’ estimated or
(extensions
actual completion
possible)
date (extensions
-Updates: every 6
possible).
months for 10
BOTH:
years from when
-Changes:
initial posting was
within 30 days of
required
the date on which
-Changes in
the RP or principal
regulatory status:
investigator
within 30 days
became aware of
after change
the change
Timing of
REGISTRY:
BOTH:
REGISTRY:
REGISTRY:
REGISTRY:
BOTH:
Posting
Not specified
In making
-Trials of drugs
-Not specified
-Not specified
Not less often than
information about
and biological
(NIH Director
(NIH Director
every 90 days.
clinical trials
products: within
ensures the
ensures the
publicly available, 30 days of
registry
registry
the Secretary shall submission
information is
information is

---

CRS-20
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
make information
-Trials of
made publically
made publically
available as soon
devices: within 30 available via
available via
as practicable after days of clearance
Internet)
Internet)
receiving the data, under section
RESULTS:
RESULTS:
and shall seek to
510(k) of the
(delays of up to 2
(delays of up to 2
be as timely and
FFDCA or
years possible if
years possible if
transparent as
approval under
seeking
seeking
possible.
sections 515 or
publication)
publication)
(Postponement
520(m) of the
-Pre-approval
-Pre-approval
and extensions for FFDCA
studies: not later
studies: not later
publication are
-Links to trial
than 30 days after
than 30 days after
possible).
results (from
approval or
approval or
FDA and NIH
issuance of not
issuance of not
information) that approvable letter
approvable letter
form the basis of
-Post-approval
-Summaries of
an efficacy claim
studies generally: medical, clinical
or are conducted
not later than 30
pharmacology
after the drug or
days after
reviews of pre-
biologic is
submission
approval and
approved or the
-Post-approval
new use studies:
device is cleared
studies of new
within 90 days of
or approved: not
uses in which the applicable date
earlier than 30
manufacturer is a -Post-approval
days after the date trial sponsor and studies generally:
of approval or
certifies it is
within 30 days of
clearance, not later seeking or will
submission
than 30 days after
seek approval
-Post-approval
the produce
within 1 year: not studies of new
becomes
later than 30 days
uses in which

---

CRS-21
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
publically
after approval,
manufacturer is a
available.
issuance of not
trial sponsor and
approvable letter,
certifies it is
or application
seeking or will
withdrawal, or 2
seek approval
years after
within 1 year: not
certification.
later than 30 days
after approval,
issuance of not
approvable letter,
or application
withdrawal; or 2
years after
certification.
Searchable By
REGISTRY:
BOTH:
REGISTRY:
REGISTRY:
REGISTRY:
BOTH:
Not specified (But for
Not specified (But -Indication, using
-Enrollment status -Trial enrollment
Not specified.
a list of required data
for a list of
Medical Subject
-Approval status
status
(But for a list of
elements, see that entry required data
Headers
RESULTS:
-Trial sponsor
required data
below.)
elements, see that
-Source of support -Each financial
RESULTS:
elements, see that
entry below.)
-Study phase
sponsor
-Status of FDA
entry below.)
-Treatment
-Clinical trial
application
-Recruitment
phase
-Trial phase
status
-Safety issue
-Product name
-Age group
-Drug name
-Each financial
(including
BOTH:
sponsor
pediatric
-Indication, using
BOTH:
subpopulations)
Medical Subject
-Indication, using
-Study location
Headers
Medical Subject

---

CRS-22
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
-National Clinical
-Sponsor
Headers
Trial number or
-Safety issue
other
being studied
identification
-Trial sponsor
number
Trials Included
REGISTRY:
REGISTRY:
REGISTRY:
REGISTRY:
BOTH:
BOTH:
-Investigational new
- Non-phase I
-Device trials:
-Premarket:
-Drug, device,
-Preapproval:
drug trials: trials
clinical trials of
prospective study
Trials to verify
biologic clinical
Studies required
(whether federally or
drugs, devices,
of health
efficacy and
trials: Trials
by the Center
privately funded) of
biologics: trials
outcomes
establish doses
testing a products’ Director of drugs
experimental
testing a treatment comparing an
-Confirmatory:
safety or
and biologics
treatments for serious
for a
intervention
All
effectiveness if
being considered
or life- threatening
life-threatening
against a control
RESULTS:
conducted in the
for FDA approval
diseases and conditions disease or
in human subjects
-Premarket:
U.S. or if the
under FFDCA
under regulations
condition, that are intended to
Trials to verify
product has FDA
section 505 or
promulgated pursuant
federally funded,
support an
efficacy and
approval or is the
PHSA Section 351
to section 21 USC
used in requesting application under
establish doses if
subject of an
[reapproval of
355(i) [re
FDA approval,
section 520 (m)
recommended by a application for
drugs and
investigational new
and/or conducted
[re humanitarian
required GAO
FDA approval.
biologics]
drugs].
in the United
devices] or 515 [re study and required
-Postmarket:
-Treatment use of
States.
premarket
by the HHS
Studies required
investigational new
RESULTS:
approval of
Secretary through
by the Center
drugs:
- Non-phase I
devices] or a
rulemaking;
Director of drugs
information pertaining
Drug, device, or
report under
fast track product
approved by FDA
to experimental
biologic clinical
section 510(k) [re
trials if used as the
under FFDCA
treatments for serious
trials, and those
device clearance]
basis for efficacy.
section 505, or
or life-threatening
required by the
of the FFDCA;
-Confirmatory:
biologics licensed
diseases and conditions HHS Secretary in pediatric
Premarket
by FDA under

---

CRS-23
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
that may be available - the interest of
postmarket
confirmatory trials
FFDCA section
(i) under a treatment
public health: if
surveillance as
BOTH:
351.
investigational new
federally funded,
required under
-Postmarket: all.
drug application that
used in requesting section 522 of the
-Pediatric
has been submitted to
FDA approval,
FFDCA (as
Pharmacokinetic:
the Secretary under 21
and/or
amended by the
all
USC 360bbb(c); or
conducted in the
bill).
(ii) as a Group C cancer United States.
-Drug and
drug (as defined by the
BOTH:
biologic trials: a
National Cancer
clinical trial
controlled clinical
Institute).
means a research
investigation of a
study in human
product subject to
volunteers to
section 505 [re
answer specific
drug approval] or
health questions,
351 [re approval
including
of biological
treatment,
products] of the
prevention,
FFDCA.
diagnostic,
-Other trials:
screening, and
voluntary
quality-of-life
submissions may
trials
be made.
Exceptions
REGISTRY:
BOTH:
REGISTRY:
BOTH:
BOTH:
None.
(trials not
Information relating to -Phase I clinical
-Device trials:
-Exploratory
-Pharmacokinetic
included)
an investigation if the
trials conducted
limited studies to
trials solely to
and toxicity
sponsor has provided a
solely to test the
gather essential
assess safety,
studies: a clinical
detailed certification to safety of an
information used
evaluate
trial to determine
the Secretary that
unapproved drug
to refine the
pharmacokinetics, the safety of a use
disclosure would
or unlicensed
device or design a
or verify efficacy
of a drug that is

---

CRS-24
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
substantially interfere
biological product, pivotal trial and
-Observational
designed solely to
with the timely
pilot or feasibility
that is not
studies
detect major
enrollment of subjects
studies conducted
intended to
toxicities in the
in the investigation,
to confirm the
determine safety
drug or to
unless the Secretary,
design and
and effectiveness
investigate
after the receipt of the
operating
of a device.
pharmacokinetics,
certification, provides
specifications of
-Drug and
unless the clinical
the sponsor with a
an unapproved or
Biologic Trials:
trial is designed to
detailed written
not yet cleared
Phase I trials.
investigate
determination that such medical device
pharmacokinetics
disclosure would not
may be included
in a special
substantially interfere
with RP consent.
population or
with such enrollment.
-Clinical trials of
populations; and
other health-
-Feasibility
related
studies: a small
interventions may
clinical trial to
be included with
determine the
consent of RP.
feasibility of a
device, or a
clinical trial to test
prototype devices
where the primary
focus is feasibility.
Registry Data
-Purpose of each
-Trial title
-WHO elements
-Sponsor
-WHO elements
-Type of study
Elements
experimental drug
-Unique identifier
(See Appendix
-Trial purpose
(See Appendix
-Nature of study
-Eligibility criteria
-Trial description
A.)
-Patient
A.)
-Primary and
-Location of trial sites
-Trial phase
-City, state, zip
population
-City, state, zip
secondary
-Point of contact for
-Trial type
code of study
description
code of study
outcomes
enrollment
-Trial purpose
-Toll free number
-General
-Estimated
-Date the Center

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CRS-25
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
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-Description of whether -Primary,
for study
description of
completion date
Director required
and how the
secondary
-Whether there is
results, trial design -RP identity and
the study or that
manufacturer or
outcome measures expanded access
changes, and
contact
the sponsor agreed
sponsor will respond to -Date outcome
for unapproved
reasons for
information
to the study
requests for protocol
measures will be
drugs and
changes
-Whether there is
-Deadline for
exception, with
assessed
biologics under
-WHO elements
expanded access
study completion
appropriate safeguards, -Dates and details
FFDCA section
(See Appendix
for unapproved
-If deadline not
for single- patient and
of revisions to
561 [re emergency A.)
drugs and
met, explanation
expanded protocol use
outcomes
situations, patient
-City, state, zip
biologics under
of why not
of the new drug,
-Eligibility and
access to
code of study
FFDCA section
-Study progress
particularly in children
exclusion criteria
treatments for
-Whether
561 [re emergency reports
-With sponsor consent,
-Whether and how serious diseases,
compassionate use situations, patient
-Center Director
may include
requests for
treatment uses]
is available
access to
determinations
information about the
single-patient and
-Other data
-Elements
treatments for
(with reasons,
results of included
expanded protocol elements as
specified by
serious diseases,
references,
trials, including
use (particularly in appropriate
Secretary
treatment uses]
supporting
potential toxicities or
children) will be
-Links to results
-Restrictions on
materials) about
adverse effects
addressed
from certain FDA
non-employees’
whether the
-Trial and
submissions, NIH
discussion or
product presents
enrollment status
information
publication of
an unreasonable
at individual sites
(Medline cites and
results
public risk, and
-Estimated
NLM database of
-Elements
required corrective
completion date
product labels),
specified by
action
-Trial location
and previously
Secretary
-RP identity and
existing databank
contact
entries
information
-Sponsor
-Funding source
-Experimental

---

CRS-26
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
treatments for
serious or life-
threatening
conditions
available under a
treatment
investigational
new drug
application or as a
Group C cancer
drug.
Results Data
None.
-Title
None.
-Indication studied -Indication studied -Type of study
Elements
-Unique identifier
-Safety issue
-Safety issue
-Nature of study
-Product tested
-Status of FDA
-Status of FDA
-Primary and
-Trial description
application
application
secondary
in lay language
-Trial phase
-Trial phase
outcomes
-Trial phase, type
TECHNICAL
TECHNICAL
-Date the Center
-Trial purpose
REPORT:
REPORT:
Director required
-Demographic
-Each sponsor
-Each sponsor
the study or that
data
-Scientific point of -Scientific point of the sponsor agreed
-Estimated
contact
contact
to the study
completion date
-Description of
-Description of
-Deadline for
-Study sponsor
patient population patient population study completion
and funding
-Summary of
-Summary of
-If deadline not
source
aggregate data
aggregate data
met, explanation
-Primary,
assessing primary
assessing primary
of why not
secondary
and secondary
and secondary
-Study progress
outcome measures
endpoints, safety
endpoints, safety
reports
-Date outcome
information
information
-Center Director

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CRS-27
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
measures assessed
-Information about -Information about determinations
-Dates, details of
subjects quit trial
subjects quit trial
(with reasons,
outcome revisions
-Restrictions on
-Restrictions on
references,
-Actual
non-employees’
non-employees’
supporting
completion date,
discussion or
discussion or
materials) about
reason for
publication of
publication of
whether the
difference from
results.
results.
product presents
estimate
-Link to peer
-Link to peer
an unreasonable
-If terminated,
reviewed
reviewed
public risk, and
reason for
publications
publications
required corrective
termination
-completion date
-completion date
action
-Results summary
-FDA adverse
-FDA adverse
with trial design,
regulatory action
regulatory action
methodology,
NONTECHNI-
NONTECHNI-
outcome
CAL REPORT:
CAL REPORT:
measures,
-Point of contact
-Point of contact
summary data
-General
-General
tables, statistical
description of
description of
significance of
results, trial design results, trial design
results
changes, and
changes, and
-Safety data,
reasons for
reasons for
including adverse
changes
changes
event information
BOTH
BOTH
-Peer-reviewed
REPORTS:
REPORTS:
publications
-Trial purpose
-Trial purpose
-Description of
-Trial sponsor
-Trial sponsor
results review
-General
-General
process, protocol
description of
description of
-Status of FDA
results, trial design results, trial design
application or
changes, and
changes, and

---

CRS-28
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
reason trial not
reasons for
reasons for
submitted to FDA
changes
changes
Enforcement
REGISTRY:
BOTH:
REGISTRY:
BOTH:
BOTH:
BOTH:
and Corrections None specified.
-Sponsors of FDA -RP ensures
-RP ensures
-RP ensures
-A product is
General mechanisms
new drug
submissions not
submissions not
submissions not
considered
for enforcing
applications
false or
false or
false or
misbranded if a
compliance with FDA
submit to
misleading.
misleading.
misleading.
sponsor fails to
requirements may be
Secretary
-No federal
-No federal
-No federal
comply with an
applicable, but have not certification of
agency may
agency may
agency may
order or
been applied by FDA.
compliance with
release research
release grant funds release research
requirement of the
FFDCA. If not,
grant funds to
to noncompliant
grant funds to
act.
after hearing,
noncompliant RPs. RPs.
noncompliant RPs. -Other penalties
Secretary imposes -For applicable
-FDA
-For applicable
are created for
$10,000/day civil
trials funded by
Commissioner
trials funded by
failure to conduct
monetary penalty
FDA, NIH,
verifies required
FDA, NIH,
required studies.
until certification
AHRQ, or VA,
submissions were
AHRQ, or VA,
submitted. If
progress report
made when
progress report
information is
forms include
considering
forms include
inaccurate and
certification of
applications for
certification of
sponsor knew or
compliance.
investigational
compliance.
should have
Agency heads
drug exemptions,
Agency heads
known, after
verify compliance
new drug
verify compliance
notice and
before releasing
approvals,
before releasing
hearing, Secretary grant funds to
biologics licences. grant funds to
orders sponsor to
RPs. Secretary
After notice to RP, RPs. Secretary
pay civil monetary consults with
opportunity to
consults with
penalty of
other federal
correct, Secretary
other federal
$100,000 to
agencies to
refuses to file
agencies to
$2,000,000 for any determine whether application.
determine whether

---

CRS-29
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
30-day period.
studies funded by
-Secretary checks
studies funded by
-To be eligible for them and
registry to ensure
them and
a federal grant,
conducted under
corresponding
conducted under
contract, or
45 CFR 46 [re
results are filed.
45 CFR 46 [re
cooperative
federal protections After notice to RP, federal protections
agreement,
for human
opportunity to
for human
principal
subjects] merit
correct, Secretary
subjects] merit
investigator
similar
reports
similar
certifies Act
procedures.
noncompliance to
procedures.
compliance.
-Applications or
federal agencies
-NIH Director
Noncompliance,
submissions under and Office of
checks registry to
after notice, leads
FFDCA sections
Human Research
ensure
to ineligibility,
505, 515, 520(m),
Protections, posts
corresponding
posting of
351, or 510(k) [re
notice of
results are filed.
noncompliance
new drugs,
noncompliance in
After notice to RP,
notice in database. biologics and
registry and
opportunity to
devices], must
database.
correct, Director
-In trial with
have certifications -Secretary ensures reports
nonfederal
of compliance.
content is not false noncompliance to
support, Act
-Secretary may
or misleading and
federal agencies
noncompliance
impose FFDCA
non-promotional
and Office of
leads to notice,
penalties for
by checking a
Human Research
opportunity to
noncompliance.
representative
Protections, posts
correct, hearing,
sample. After
notice of
$10,000/day
notice to RP,
noncompliance in
penalty until
opportunity to
registry and
compliant.
correct, Secretary
database.
may impose
-Applications or
FFDCA penalties
submissions under
FFDCA sections

---

CRS-30
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
505, 515, 351, or
510(k) [re new
drugs, biologics
and devices], must
have certifications
of compliance.
-Secretary may
impose FFDCA
penalties for
noncompliance,
including civil
monetary penalties
($10,000/day for
first violation,
$20,000/day for
each subsequent
violation) created
by Act.
Required
None.
BOTH:
RESULTS:
RESULTS:
None required by
HHS Secretary
Studies or
Not later than 1
The NIH Director
Not earlier than 2
clinical trials title. required to report
Reports
year after
conducts a study
years after results
to Congress on
enactment,
to determine the
database
device postmarket
Secretary submits
best, validated
established,
safety within 6
to appropriate
methods of
Comptroller
months of
committees of
making trial
General initiates a
enactment.
Congress a report
results public after GAO study of
on the status of the the approval of a
inclusion of
implementation of drug that is the
certain premarket
Act requirements
subject of an
trials: burden to

---

CRS-31
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
including number
applicable drug
sponsors and
and types of trials
trial. Director
agencies, benefit
submitted.
submits findings
to patients and
REGISTRY:
to the HHS
health providers,
Secretary
Secretary within
recommendations.
contracts with
18 months of
Makes report to
IOM to conduct a
initiating the
HELP, Energy and
study of the extent study.
Commerce.
to which data
submitted to the
registry and
database have
impacted the
public health. Not
later than 6
months after the
contract date, IOM
submits study to
Secretary
Authorized
REGISTRY:
BOTH:
BOTH:
BOTH:
BOTH:
For entire Act:
Appropriations
Such sums as may be
Such sums as may $10,000,000 each
$10,000,000 each
$10,000,000 each
FY2008:
necessary; Fees
be necessary
FY
FY
FY
$50,000,000
collected under section
FY2009:
21 USC 379h [re FDA
$75,000,000
prescription drug user
FY2010:
fees] may not be used
$100,000,000
for the registry.
FY2011:
$125,000,000
FY2012:
$150,000,000

---

CRS-32
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
Preemption
None.
None.
BOTH:
BOTH:
BOTH:
None.
Yes. No state or
Yes. No state or
Yes. No state or
political
political
political
subdivision of a
subdivision of a
subdivision of a
state may require
state may require
state may require
or effect
or effect
or effect
registration of
registration of
registration of
trials or results.
trials or results.
trials or results.
Safe Harbor
None.
None.
BOTH:
BOTH:
BOTH:
None.
Somewhat.
Somewhat.
Somewhat.
Compliant
Compliant
Compliant
submissions shall
submissions shall
submissions shall
not be considered
not be considered
not be considered
(1) by Secretary as (1) by Secretary as (1) by Secretary as
evidence of a new evidence of a new evidence of a new
intended use
intended use
intended use
different from
different from
different from
labeling, or (2) as
labeling, or (2) as
labeling, or (2) as
FFDCA labeling,
FFDCA labeling,
FFDCA labeling,
adulteration, or
adulteration, or
adulteration, or
misbranding.
misbranding.
misbranding.
Effective Dates
REGISTRY:
Not specified.
REGISTRY:
BOTH:
BOTH:
Not specified.
Currently operational
-Generally:
Databases to be
-Databases
October 1, 2007
established not
established not
-Regulations
later than 1 year
later than 1 year
become effective
after enactment.
after enactment.
90 days after
issuance of HHS
Secretary’s

---

CRS-33
S. 468 /
Current Law
S. 467
S. 1082
S. 484
H.R. 1561
H.R. 788
issuance of final
rule. (Final rule
issued pursuant to
Act to be issued
not later than 18
months after Act’s
enactment, and
after notice and
comment.)
-Funding
restrictions take
effect 210 days
after regulations’
effective date.

---

CRS-34
Appendix A. World Health Organization,
International Clinical Trials Registry Platform,
Registration Data Set (Version 1.0)
ITEM
DEFINITION / EXPLANATION
Primary
Name of Primary Register, and the unique ID number assigned by the Primary
Register and
Register to this trial.
Trial ID #
Date of
Date when trial was officially registered in the Primary Register YYYY/MM/DD.
Registration in
Primary
Register
Secondary ID#s
Other identifying numbers and issuing authorities besides the Primary Register, if
any. Include the sponsor name and sponsor-issued trial number (e.g., protocol
number) if available. Also include other trial registers that have issued an ID
number to this trial. There is no limit on the number of Secondary ID numbers that
can be provided.
Source(s) of
Major source(s) of monetary or material support for the trial (e.g., funding agency,
Monetary or
foundation, company).
Material
Support
Primary
The individual, organization, group or other legal person taking responsibility for
Sponsor
securing the arrangements to initiate and/or manage a study (including arrangements
to ensure that the study design meets appropriate standards and to ensure
appropriate conduct and reporting). In commercial trials, the primary sponsor is
normally the main applicant for regulatory authorization to begin the study. It may
or may not be the main funder.
Secondary
Additional individuals, organizations or other legal persons, if any, that have agreed
Sponsor(s)
with the primary sponsor to take on responsibilities of sponsorship.
A secondary sponsor may have agreed
-to take on all the responsibilities of sponsorship jointly with the primary sponsor;
or
-to form a group with the primary sponsor in which the responsibilities of
sponsorship are allocated among the members of the group; or
-to act as the sponsor’s legal representative in relation to some or all of the trial
sites; or
-to take responsibility for the accuracy of trial registration information submitted.
Contact for
Email address, telephone number, or postal address of the contact who will respond
Public Queries
to general queries, including information about current recruitment status
Contact for
Email address, telephone number, or postal address, and affiliation of the person to
Scientific
contact for scientific queries about the trial (e.g., principal investigator, medical
Queries
director employed by the sponsor). For a multi-center study, enter the contact
information for the lead Principal Investigator or overall scientific director.
Public Title
Email address, telephone number, or postal address, and affiliation of the person to
contact for scientific queries about the trial (e.g., principal investigator, medical
director employed by the sponsor). For a multi-center study, enter the contact
information for the lead Principal Investigator or overall scientific director.

---

CRS-35
Scientific Title
Scientific title of the study as it appears in the protocol submitted for funding and
ethical review. Include trial acronym if available.
Countries of
The countries from which participants will be, are intended to be, or have been
Recruitment
recruited.
Health
Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer,
Condition(s) or
medication error). If the study is conducted on healthy human volunteers belonging
Problem(s)
to the target population of the intervention (e.g., preventative or screening
Studied
interventions), enter the particular health condition(s) or problem(s) being
prevented. If the study is conducted using healthy human volunteers not belonging
to the target population (e.g., a preliminary safety study), an appropriate keyword
will be defined for users to select.
Intervention(s)
Enter the specific name of the intervention(s) and the comparator/control(s) being
studied. Use the International Non-Proprietary Name if possible (not brand/trade
names). For an unregistered drug, the generic name, chemical name, or company
serial number is acceptable. If the intervention consists of several separate
treatments, list them all in one line separated by commas (e.g., “low-fat diet,
exercise”).
The control intervention(s) is/are the interventions against which the study
intervention is evaluated (e.g., placebo, no treatment, active control). If an active
control is used, be sure to enter in the name(s) of that intervention, or enter
“placebo” or “no treatment” as applicable.
For each intervention, describe other intervention details as applicable (dose,
duration, mode of administration, etc).
Key Inclusion
Inclusion and exclusion criteria for participant selection, including age and sex.
and Exclusion
Criteria
Study Type
A single arm study is one in which all participants are given the same intervention.
Trials in which participants are assigned to receive one of two or more interventions
are NOT single arm studies. Crossover trials are NOT single arm studies.
A trial is “randomized” if participants are assigned to intervention groups using a
method based on chance (e.g., random number table, random computer-generated
sequence, minimization, adaptive randomization).
Date of First
Anticipated or actual date of enrollment of the first participant (YYYY/MM).
Enrollment
Target Sample
Number of participants that this trial plans to enroll.
Size
Recruitment
Recruitment status of this trial.
Status
-Pending: participants are not yet being recruited or enrolled at any site
-Active: participants are currently being recruited and enrolled
-Temporary halt: there is a temporary halt in recruitment and enrollment
-Closed: participants are no longer being recruited or enrolled
Primary
Outcomes are events, variables, or experiences that are measured because it is
Outcome(s)
believed that they may be influenced by the intervention. The Primary Outcome
should be the outcome used in sample size calculations, or the main outcome(s)
used to determine the effects of the int[ervention(s).
Enter the names of all primary outcomes in the trial as well as the pre-specified
timepoint(s) of primary interest. Be as specific as possible with the metric used
(e.g., “% with Beck Depression Score > 10" rather than just “depression”).
Examples:
Outcome Name: all-cause mortality, Timepoints: 5 years; or Outcome Name: Mean
Beck Depression Score, Timepoint: 18 weeks

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CRS-36
Secondary
Secondary outcomes are events, variables, or experiences that are of secondary
Outcome(s)
interest or that are measured at timepoints of secondary interest. A secondary
outcome may involve the same event, variable, or experience as the primary
outcome, but measured at timepoints other than those of primary interest (e.g.,
Primary outcome: all-cause mortality at 5 years; Secondary outcome: all-cause
mortality at 1 year, 3 years), or may involve a different event, variable, or
experience altogether (e.g., Primary outcome: all-cause mortality at 5 years;
Secondary outcome: hospitalization rate at 5 years).
Enter the name and timepoint(s) for all secondary outcomes of clinical and/or
scientific importance. Be as specific as possible with the metric used (e.g., “% with
Beck Depression Score > 10" rather than just “depression”). Examples: Outcome
Name: all-cause mortality, Timepoints: 6 months, 1 year; or Outcome Name: Mean
glycosylated hemoglobin A1C, Timepoints: 4 and 8 weeks
Source: WHO, ICTRP, “Registration Data Set (version 1.0),” (March 16, 2007), at [http://www.who.
int/ictrp/data_set/en/index1.html], visited Apr. 16, 2007.

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