Clinical Trials Reporting and Publication

Clinical Trials Reporting and Publication
Updated July 12, 2007
Erin D. Williams
Specialist in Bioethical Policy
Domestic Social Policy Division

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.
Nine relevant bills have been introduced during the 110^th Congress, two of
which also reauthorize key Food and Drug Administration programs. These bills are
the Food and Drug Administration Revitalization Act (S. 1082), which the Senate
passed on May 9, 2007, and the Food and Drug Administration Amendments Act of
2007 (H.R. 2900), which the House passed on July 11, 2007. Both bills would
require the registration of clinical trials, some of which must currently be registered
at [http://clinicaltrials.gov]. H.R. 2900 would also require the subsequent posting of
clinical trial results. Differences between the two bills are expected to be addressed
in conference. Seven other bills also contain relevant provisions: S. 467, S. 484/H.R.

1561, S. 468/H.R. 788, and S. 830/H.R. 1494.

This report will be updated on a regular basis.

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
FDA User Fee Reauthorization Legislation (S. 1082 and H.R. 2900) .....9
Other Clinical Trials Bills.......................................9
Registry ................................................10
Results Database.........................................11
Issues ......................................................11
Goals ..................................................11
Appropriateness/Presentation ...............................11
Timing .................................................12
Voluntary or Mandatory/Penalties............................12
Conflicts of Interest.......................................12
Devices .................................................12
Appendix A. World Health Organization, International Clinical Trials
Registry Platform, Registration Data Set (Version 1.0)................35
List of Tables
Table 1. Comparison of Proposals for Clinical Trials Reporting and
Publication in the 110^th Congress.................................14

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 are¹
adequate. This report focuses on the first of these questions.
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; the²
results of negative or inconclusive trials often go unpublished. 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.

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...)

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 to⁸
the National Library of Medicine’s (NLM’s) PubMed Central. (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 materials⁹

generated by NIH-funded research.
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...)

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, 108^th Cong., 2^nd 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/
drugsbiologi cs.html ].
¹³ Shankar Vedantam, “Drugmakers Prefer Silence on Test Data,” Washington Post, July 6,
(continued...)

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. A1.

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].
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 ].

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 some²⁰
required data elements. 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 identification²¹
number. 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/].

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
[ h t t p : / / www.who.i nt / bul l e t i n / vol umes/ 82/ 5/ en/ 321.pdf ] .
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].

[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 physician²⁴
researchers to present, publish, and disseminate data from clinical trials. 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 of²⁵
clinical trials. 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 the²⁶
heads of NIH and FDA.
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,²⁸
conducted a workshop on developing a national clinical trials registry. Workshop
participants presented a range of views on the need for registries, registry content,

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
[ ht t p: / / www.ama-assn.or g/ ama/ pub/ cat e gor y/ pr i nt / 13909.ht ml ] .
²⁶ “Senators Call for National Registry of Clinical Drug Trials,” Senator Tim Johnson, press
release, July 8, 2004, at [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].
²⁸ Committee on Clinical Trials, Institute of Medicine of the National Academies,
Developing a National Registry of Pharmacologic and Biologic Trials (Washington, DC:
The National Academies Press, 2006), at [http://books.nap.edu/catalog/11561.html#toc].

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 disclose³⁰
summary results of all industry-sponsored clinical trials. 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
Legislation
A number of bills related to clinical trials reporting and publication have been
introduced in the 110^th Congress.

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].
³⁰ The announcement was made jointly with PhRMA, the European Federation of
Pharmaceutical Industries and Associations (EFPIA), and the Japanese Pharmaceutical
Manufacturers 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
[ h t t p : / / www.i f pma.or g/ News/ NewsRel easeDet ai l . 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
[ h t t p : / / www.i f pma .or g/ c l i n i c a l t r i a l s .ht ml ] .

FDA User Fee Reauthorization Legislation
(S. 1082 and H.R. 2900)
Two major pieces of legislation, which would reauthorize FDA drug and
medical device user fee authorities, contain clinical trials databank titles or subtitles.
Each bill has been passed by its respective chamber of Congress, leaving differences
between the bills to be addressed in conference. The Food and Drug Administration
Reauthorization Act (S. 1082), introduced by Senator Kennedy, passed the Senate on
May 9, 2007. The bill is composed of titles on the topics of reauthorizing the
Prescription Drug User Fee Act and the Medical Device User Fee Act, promoting
drug safety, encouraging the development of pediatric medical drugs and devices,
addressing drug importation, promoting food safety, and enabling domestic pet turtle
market access. One subtitle of the drug safety provisions (Title II, Subtitle C) would
create a clinical trial registry and could lead to the creation of a results database
following rulemaking by the HHS Secretary.
The Food and Drug Administration Amendments Act of 2007 (H.R. 2900),
introduced by Representative Pallone on June 28, 2007, passed the House on July 11,
2007. H.R. 2900 is similar to S. 1082, but does not contain provisions related to drug
importation, food safety, or domestic pet turtle market access. Its title on clinical
trials databanks (Title VIII) would require both the registration of clinical trials and
the posting of their results. One controversial provision that was dropped from H.R.
2900 (and was never present in S. 1082) specified that Act would not have had any
legal effect on — and thus would have allowed — causes of action for damages
under state law.
Other Clinical Trials Bills
One bill introduced in the 110^th Congress is solely focused on clinical trials
registration and reporting: S. 467, the Fair Access to Clinical Trials (FACT) Act,^th
introduced by Senator Dodd. Similar legislation was introduced in the 109
Congress by Senator Dodd (S. 470) and Representative Waxman (H.R. 3196), and^th
in the 108 Congress by Senator Dodd (S. 2933) and Representative Markey (H.R.

5252).

Several other bills focused on promoting drug and device safety at the FDA
contain clinical trials databank provisions as well. The Enhancing Drug Safety and
Innovation Act of 2007 (S. 484/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. This measure 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 postmarket 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
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. 1082, H.R. 2900, S. 467, 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 similar reasons, S. 468/H.R. 788 is not
incorporated into the 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. 1082, H.R. 2900, S. 467, 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
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 industry³²
consensus. All of the bills would contain information accessible to both the general
public and professionals. Three bills, H.R. 2900, 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. 1082 and S. 467 would generally require registration within
21 days that a trial is opened for enrollment. H.R. 2900, S. 484, and H.R. 1561
would require enrollment within 14 days after the first patient is enrolled, except for

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].

medical device clinical trials. H.R. 2900 would not allow the public release of the
information until the device is approved or cleared by FDA. S. 467/H.R. 788 would
require that information about the study be posted not less frequently than every 90
days.
For clinical trial results, H.R. 2900, 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. S. 1082 does not create
a results databank and, therefore, does not specify when results would have to be
released.
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 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-14
Table 1. Comparison of Proposals for Clinical Trials Reporting and Publication in the 110^th Congress
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
TitleData bank ofFood and DrugFood and DrugFACT ActFood and DrugEnhancing Drug
information onAdministrationAdministrationAdministrationSafety and
clinical trials forRevitalization ActAmendments ActRevitalization ActInnovation Act of
drugs for serious orof 2007 2007
life-threatening
diseases and
conditions
ⁱ^{ki/CRS-RL32832}
^g/wSponsorSenator KennedyRepresentativeSenator DoddSenator EnziRepresentative
^s^.or Pallone Waxman
^le^ak
Law Amended(Existing law) PHSAPHSA (42 U.S.C.PHSA Title IV (42PHSA (42 U.S.C.Subsection (i) ofSubsection (i) of
^://wiki(42 U.S.C. § 282 (j))282), as amended;U.S.C. 281, et seq.)282), as amendedsection 402 ofsection 402 of
^h^ttpand Section 492by Public LawPHSA (42 USCPHSA (42 USC
A(a) of the PHSA109-482; and282 as amended282), as amended
Section 492 A(a)by PL 109-482).by PL 109-482.
of the PHSA
Registry and/orRegistry onlyRegistry expanded,Both.BothBothBoth

Results(clinicaltrials.gov);and includes links
Databasewith sponsor consent,to certain results.
Requiredregistry may alsoResults database to
include informationbe created by HHS
about the results ofSecretary
registered trials,rulemaking

CRS-15
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
including potentialfollowing
toxicities or adverserecommendations
effectsto be made in NIH
Director’s report
about best,
validated method of
making trial results
publically
available.
ⁱ^{ki/CRS-RL32832}Product TrialREGISTRY:REGISTRY:BOTH:BOTH:BOTH:BOTH:
^g/wTypes IncludedDrugsDrugs, devices, Drugs, devices, Drugs, biologics,Drugs, biologics,Drugs, devices,
^s^.or
^le^akbiologicsand biologics.devices. eventuallybiologics
Information aboutpossibly devices
^://wikiother trials may be
^h^ttp voluntarily
submitted.
Public AccessREGISTRY: REGISTRY:BOTH: BOTH:BOTH:BOTH:
Yes, via informationYes, via Internet. Yes, via Internet. Yes, viaYes, via Internet. Yes, via Internet.
systems, which are toInternet posting andFOIA requestinformationInternet postingFOIA request
include toll-freeFOIA requestdisclosures notsystems, which areand FOIA requestdisclosures not
telephonedisclosures limitedavailable for resultsto include toll-freedisclosures limitedavailable for
communicationsto terms of the act. for which thetelephoneto terms of the act. results for which
Secretaryprincipalcommunications. Secretarythe principal
promulgatesinvestigator isProvisions relatedpromulgatesinvestigator is
regulations thatseekingto disclosure ofregulations thatseeking

CRS-16
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
notice of posting bepublication. FDA reviewsnotice of postingpublication.
part of informedOld versions ofsupersede FOIA.be part of
consent.updated postingsinformed consent.
remain available,
with trackable
changes the public
can see.
Location ofREGISTRY:REGISTRY:BOTH: NLM andBOTH:BOTH:BOTH:
ⁱ^{ki/CRS-RL32832}Databases NLM at NIH iscurrent locationNLM at NIHNIHREGISTRY: Not specified, butbill amends theNIH. REGISTRY: NIH. REGISTRY:
^g/wEither supplants orportion of theEither supplants orEither supplants or
^s^.or
^le^akbuilds onUSC related to thebuilds onbuilds on
clinicaltrials.gov,current registry,clinicaltrials.gov,clinicaltrials.gov,
^://wikiwhichever is morewhich is located atwhichever is morewhichever is more
^h^ttpefficient.NLM at NIH.efficient.efficient.
Links BetweenREGISTRY:REGISTRY:BOTH:Not specified,REGISTRY:BOTH:
Registry,Not specified; exceptEntries link toCorrespondingexcept that theEntries link toCorresponding
Resultsthat the activities ofcertain existingregistry and resultsSecretary shallresults entries.registry and
Databasethe data bank are toresults.database entriesassign eachresults database
be integrated andlink to one another.clinical trial aentries link to one
coordinated withunique identifieranother.

related activities ofto be included in
other agencies of thethe registry and in
DHHS, and, to thethe database.
extent practicable,

CRS-17
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
coordinated with
other data banks
containing similar
information.
Who SubmitsREGISTRY:REGISTRY:BOTH:BOTH:BOTH:BOTH:
InformationSponsorResponsible partyResponsible partyResponsible partyResponsible partyResponsible party
(RP): sponsor; if no(RP): primary(RP): if such(RP): sponsor, or(RP): primary
sponsor exists-sponsor as definedclinical trial is theprincipalsponsor as defined
ⁱ^{ki/CRS-RL32832}grantee, contractoror awardee ofby WHO, orprincipalsubject of aninvestigationalinvestigator ifdesignated byby WHO, orprincipal
^g/wfederal funding; ifinvestigator (PI) ifnew drugsponsorinvestigator (PI) if
^s^.or
^le^akdesignated bydesignated byapplication or andesignated by
sponsor, grantee,sponsor and if PI isapplication for ansponsor and if PI
^://wikicontractor or responsible forinvestigationalis responsible for
^h^ttpawardee - principalconducting thedevice exemption conducting the
investigator.trial, has access to — the sponsor; iftrial, has access to
and control overnot — the personand control over
data, has the rightthat provides thedata, has the right
to publish triallargest share ofto publish trial
results, and has themonetary support,results, and has
responsibility tobut if that personthe responsibility
meet the RPis federal or stateto meet the RP
responsibilities.agency — theresponsibilities.

principal
investigator; if the
main funder is a
nonprofit — the

CRS-18
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
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
ⁱ^{ki/CRS-RL32832}monetary support
^g/wfor the trial is
^s^.orresponsible for the
^le^akconduct of the trial
and will be
^://wikiresponsible for
^h^ttp submitting
required trial
information —
that person.

CRS-19
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
Who ReceivesREGISTRY:REGISTRY:BOTH:BOTH:BOTH:BOTH:
Information HHS Secretary,Director of NIHDirector of NIHHHS Secretary,Director of NIHDirector of NIH
acting through theacting through the
NIH DirectorNIH Director
Timing ofREGISTRY:REGISTRY:REGISTRY:REGISTRY: REGISTRY: REGISTRY:
Submission Not later than 21-Initially: not later-Initially: not later-Initially: not-Initially: not-Initially: not
days after thethan 21 days afterthan 14 days afterlater than 21 dayslater than 14 dayslater than 14 days
approval of thethe first patient isfirst patient isafter the trial isafter first patientafter first patient
protocolenrolled.enrolledopened foris enrolledis enrolled
-Change in-Updates: not lessenrollment.-Change in-Updates: not less
ⁱ^{ki/CRS-RL32832}enrollment status:not later than 30than once every 6monthsRESULTS:-Initially: impliedEnrollmentStatus: not laterthan once every 6months
^g/wdays after change.-Change insame date as forthan 30 days after-Change in
^s^.or-Completion ofEnrollmentregistry. (To thechangeEnrollment
^le^aktrial: not later thanStatus: not laterextent practicable,-FinalStatus: not later
^://wiki30 days after thethan 30 days afterthe SecretarySubmission: Notthan 30 days after
^h^ttplast patient enrolledchangeensures that wherelater than 30 dayschange
in the clinical trial-Notice of trialthe sameafter last enrolled-Notice of trial
has completed hiscompletion: Notinformation ispatient has lastcompletion: Not
or her last medicallater than 30 daysrequired for themedical visitlater than 30 days
visit, whether theafter finalregistry and theRESULTS:after final
clinical trialcollection of datadatabase (such as-Generally: Notcollection of data
conductedfrom subjects forinitial informationlater than 1 yearfrom subjects for
according to theprimary andrequired for theafter last enrolledprimary and
prespecifiedsecondarydatabase), apatient has lastsecondary
protocol or planoutcomesprocess exists tomedical visitoutcomes
was terminatedRESULTS:allow the RP to(extensionsRESULTS:
(extensions-Generally: Notmake only onepossible).-Generally: Not
possible).later than 1 yearsubmission.-Changes inlater than 1 year

CRS-20
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
after earlier of-Results: not laterregulatory status:after earlier of
estimated or actualthan 1 year thanwithin 30 daysestimated or actual
completion datethe earlier of theafter changecompletion date
(extensionstrials’ estimated or(extensions
possible)actual completionpossible)
-Updates: every 6date (extensions-Updates: every 6
months for 10 yearspossible).months for 10
from when initialBOTH:years from when
posting was-Changes:initial posting was
required within 30 days ofrequired
-Changes inthe date on which-Changes in
ⁱ^{ki/CRS-RL32832}regulatory status:the RP or principalregulatory status:
^g/wwithin 30 days afterinvestigatorwithin 30 days
^s^.orchangebecame aware ofafter change
^le^akthe change
^://wikiTiming ofREGISTRY:REGISTRY:REGISTRY:BOTH:REGISTRY: REGISTRY:
^h^ttpPostingNot specified-Trials of drugs-Not specifiedIn making-Not specified-Not specified
and biological(NIH Directorinformation about(NIH Director(NIH Director
products: withinensures the registryclinical trialsensures theensures the
30 days ofinformation ispublicly available, registryregistry
submissionmade publicallythe Secretary shallinformation isinformation is
-Trials of devices:available viamake informationmade publicallymade publically
within 30 days ofInternet) exceptavailable as soonavailable viaavailable via
clearance underthat NIH Directoras practicable afterInternet)Internet)
section 510(k) ofmay not makereceiving the data,RESULTS:RESULTS:
the FFDCA orregistryand shall seek to(delays of up to 2(delays of up to 2
approval underinformation aboutbe as timely andyears possible ifyears possible if
sections 515 ordevice trials publictransparent asseekingseeking

520(m) of theuntil the device ispossible.publication)publication)

CRS-21
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
FFDCA approved or cleared(Postponement-Pre-approval-Pre-approval
-Links to trialby FDA. and extensions forstudies: not laterstudies: not later
results (from FDARESULTS: (delayspublication arethan 30 days afterthan 30 days after
and NIHof up to 2 yearspossible).approval orapproval or
information) thatpossible if seekingissuance of notissuance of not
form the basis ofpublication)approvable letterapprovable letter
an efficacy claim-Pre-approval-Post-approval-Summaries of
or are conductedstudies: not laterstudies generally:medical, clinical
after the drug orthan 30 days afternot later than 30pharmacology
biologic isapproval ordays afterreviews of pre-
approved or theissuance of notsubmissionapproval and
ⁱ^{ki/CRS-RL32832}device is clearedapprovable letter -Post-approvalnew use studies:
^g/wor approved: not-Summaries ofstudies of newwithin 90 days of
^s^.orearlier than 30 daysmedical, clinicaluses in which theapplicable date
^le^akafter the date ofpharmacologymanufacturer is a-Post-approval
approval orreviews of pre-trial sponsor andstudies generally:
^://wikiclearance, not laterapproval and newcertifies it iswithin 30 days of
^h^ttpthan 30 days afteruse studies: withinseeking or willsubmission
the produce90 days ofseek approval-Post-approval
becomes publicallyapplicable date within 1 year: notstudies of new
available.-Post-approvallater than 30 daysuses in which
studies generally:after approval,manufacturer is a
within 30 days ofissuance of nottrial sponsor and
submissionapprovable letter,certifies it is
-Post-approvalor applicationseeking or will
studies of newwithdrawal, or 2seek approval
uses in whichyears afterwithin 1 year: not
manufacturer is acertification. later than 30 days
trial sponsor andafter approval,
certifies it isissuance of not

CRS-22
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
seeking or willapprovable letter,
seek approvalor application
within 1 year: notwithdrawal; or 2
later than 30 daysyears after
after approval,certification.
issuance of not
approvable letter,
or application
withdrawal; or 2
years after
certification.
ⁱ^{ki/CRS-RL32832}Searchable ByREGISTRY:REGISTRY:REGISTRY:BOTH:REGISTRY:REGISTRY:
^g/w Not specified (But-Indication, using-Trial enrollmentNot specified (But-Enrollment status -Trial enrollment
^s^.orfor a list of requiredMedical Subjectstatusfor a list of-Approval statusstatus
^le^akdata elements, seeHeaders-Trial sponsorrequired dataRESULTS: -Trial sponsor
^://wikithat entry below.) -Source of supportRESULTS:elements, see that-Each financialRESULTS:
^h^ttp-Study phase-Status of FDAentry below.)sponsor -Status of FDA
-Treatmentapplication-Clinical trialapplication
-Recruitment status-Trial phasephase -Trial phase
-Age group-Product name-Safety issue-Product name
(including pediatric-Each financial-Drug name-Each financial
subpopulations) sponsor BOTH: sponsor
-Study locationBOTH:-Indication, usingBOTH:
-National Clinical-Indication, usingMedical Subject-Indication, using
Trial number orMedical SubjectHeaders Medical Subject
other identificationHeaders-SponsorHeaders
number-Safety issue being-Safety issue
studiedbeing studied
-Trial sponsor

CRS-23
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
Trials IncludedREGISTRY:REGISTRY:BOTH:REGISTRY:REGISTRY:BOTH:
-Investigational new-Device trials:-Drug, device,- Non-phase I-Premarket:-Drug, device,
drug trials: trialsprospective studybiologic clinicalclinical trials ofTrials to verifybiologic clinical
(whether federally orof health outcomestrials: trials testingdrugs, devices,efficacy andtrials: Trials
privately funded) ofcomparing ana products’ safetybiologics: trialsestablish dosestesting a products’
experimentalintervention againstor effectiveness iftesting a treatment-Confirmatory:safety or
treatments for seriousa control in humanconducted in thefor a Alleffectiveness if
or life- threateningsubjects intended toU.S. or if thelife-threateningRESULTS:conducted in the
diseases andsupport anproduct has FDAdisease or-Premarket:U.S. or if the
conditions underapplication underapproval or is thecondition, that areTrials to verifyproduct has FDA
regulationssection 520 (m) [resubject of anfederally funded,efficacy andapproval or is the
ⁱ^{ki/CRS-RL32832}promulgated pursuanthumanitarianapplication forused in requestingestablish doses ifsubject of an
^g/wto section 21 USCdevices] or 515 [reFDA approval. FDA approval,recommended by aapplication for
^s^.or355(i) [repremarket approvaland/or conductedrequired GAOFDA approval.

^le^akinvestigational newof devices] or ain the Unitedstudy and required
drugs].report under sectionStates.by the HHS
^://wiki-Treatment use of 510(k) [re deviceRESULTS:Secretary through
^h^ttpinvestigational newclearance] of the- Non-phase Irulemaking;
drugs:FFDCA; pediatricDrug, device, or fast track product
informationpostmarketbiologic clinicaltrials if used as the
pertaining tosurveillance astrials, and thosebasis for efficacy.
experimentalrequired underrequired by the-Confirmatory:
treatments for serioussection 522 of theHHS Secretary inPremarket
or life-threateningFFDCA (asthe interest ofconfirmatory trials
diseases andamended by thepublic health: if BOTH:
conditions that maybill).federally funded,-Postmarket: all.
be available - -Drug and biologicused in requesting-Pediatric
(i) under a treatmenttrials: a controlledFDA approval,Pharmacokinetic:
investigational newclinicaland/orall
drug application thatinvestigation of aconducted in the
has been submitted toproduct subject toUnited States.

CRS-24
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
the Secretary undersection 505 [reBOTH:
21 USC 360bbb(c);drug approval] orclinical trial
or351 [re approval ofmeans a research
(ii) as a Group Cbiologicalstudy in human
cancer drug (asproducts] of thevolunteers to
defined by theFFDCA.answer specific
National Cancer-Other trials:health questions,
Institute). voluntary including
submissions maytreatment,
be made.prevention,
diagnostic,
ⁱ^{ki/CRS-RL32832}screening, and
^g/w quality-of-life
^s^.or trials
^le^akExcept i o ns REGI STRY : REGI STRY : BOTH: BOTH: BOTH: BOTH:
^://wiki(trials not Information relating-Device trials:-Pharmacokinetic-Phase I clinical-Exploratory-Pharmacokinetic
^h^ttpincluded)to an investigation iflimited studies toand toxicitytrials conductedtrials solely toand toxicity
the sponsor hasgather essentialstudies: a clinicalsolely to test theassess safety,studies: a clinical
provided a detailedinformation used totrial to determinesafety of anevaluatetrial to determine
certification to therefine the device orthe safety of a useunapproved drugpharmacokinetics,the safety of a use
Secretary thatdesign a pivotalof a drug that isor unlicensedor verify efficacyof a drug that is
disclosure wouldtrial and that is notdesigned solely tobiological product,-Observationaldesigned solely to
substantially interfereintended todetect majorpilot or feasibilitystudiesdetect major
with the timelydetermine safetytoxicities in thestudies conductedtoxicities in the
enrollment ofand effectiveness ofdrug or toto confirm thedrug or to
subjects in thea device.investigatedesign andinvestigate
investigation, unless-Drug andpharmacokinetics,operatingpharmacokinetics,
the Secretary, afterBiologic Trials:unless the clinicalspecifications ofunless the clinical
the receipt of the Phase I trials.trial is designed toan unapproved ortrial is designed to
certification, providesinvestigatenot yet clearedinvestigate

CRS-25
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
the sponsor with apharmacokineticsmedical devicepharmacokinetics
detailed writtenin a specialmay be includedin a special
determination thatpopulation orwith RP consent.population or
such disclosurepopulations; and-Clinical trials ofpopulations; and
would not-Feasibilityother health--Feasibility
substantially interferestudies: a smallrelatedstudies: a small
with such enrollment.clinical trial tointerventions mayclinical trial to
determine thebe included withdetermine the
feasibility of aconsent of RP.feasibility of a
device, or a clinicaldevice, or a
trial to testclinical trial to test
ⁱ^{ki/CRS-RL32832}prototype devicesprototype devices
^g/wwhere the primarywhere the primary
^s^.orfocus is feasibility.focus is feasibility.
^le^akRegistry Data-Purpose of each-WHO elements-WHO elements-Trial title-Sponsor-WHO elements
^://wikiElements experimental drug(See Appendix A.)(See Appendix A.)-Unique identifier-Trial purpose(See Appendix
^h^ttp-Eligibility criteria-City, state, zip-City, state, zip-Trial description-PatientA.)
-Location of trialcode of studycode, toll free-Trial phasepopulation-City, state, zip
sites-Toll free numberphone number of-Trial typedescription code of study
-Point of contact forfor studystudy-Trial purpose-General-Estimated
enrollment-Whether there is-Estimated-Primary,description ofcompletion date
-Description ofexpanded accesscompletion datesecondaryresults, trial design-RP identity and
whether and how thefor unapproved-RP identity andoutcome measureschanges, andcontact
manufacturer ordrugs and biologicscontact information-Date outcomereasons forinformation
sponsor will respondunder FFDCA-Whether there ismeasures will bechanges-Whether there is
to requests forsection 561 [reexpanded accessassessed-WHO elementsexpanded access
protocol exception,emergencyfor unapproved-Dates and details(See Appendixfor unapproved
with appropriatesituations, patientdrugs and biologicsof revisions toA.) drugs and
safeguards, foraccess tounder FFDCAoutcomes-City, state, zipbiologics under
single- patient andtreatments forsection 561 [re-Eligibility andcode of studyFFDCA section

CRS-26
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
expanded protocolserious diseases,emergencyexclusion criteria-Whether561 [re emergency
use of the new drug,treatment uses]situations, patient-Whether and howcompassionate usesituations, patient
particularly in-Other dataaccess torequests foris availableaccess to
childrenelements astreatments forsingle-patient and-Elementstreatments for
-With sponsorappropriateserious diseases,expanded protocolspecified byserious diseases,
consent, may include-Links to resultstreatment uses]use (particularly inSecretarytreatment uses]
information about thefrom certain FDA-Restrictions onchildren) will be-Restrictions on
results of includedsubmissions, NIHnon-employees’addressednon-employees’
trials, includinginformationdiscussion or-Trial anddiscussion or
potential toxicities or(Medline cites andpublication ofenrollment statuspublication of
adverse effectsNLM database ofresultsat individual sitesresults
ⁱ^{ki/CRS-RL32832}product labels), and-Elements specified-Estimated-Elements
^g/wpreviously existingby Secretarycompletion datespecified by
^s^.ordatabank entries-Trial locationSecretary

^le^ak-RP identity and
contact
^://wiki information
^h^ttp -Sponsor
-Funding source
-Experimental
treatments for
serious or life-
threatening
conditions
available under a
treatment
investigational
new drug
application or as a
Group C cancer
drug.

CRS-27
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
Results DataNone.None.-Registry data-Title-Indication studied-Indication studied
Elementselements, plus:-Unique identifier-Safety issue-Safety issue
TECHNICAL-Product tested-Status of FDA-Status of FDA
SUMMARY:-Trial descriptionapplicationapplication
-Each sponsorin lay language-Trial phase-Trial phase
-Scientific point of-Trial phase, typeTECHNICALTECHNICAL
contact-Trial purposeREPORT:REPORT:
-Description of-Demographic-Each sponsor-Each sponsor
patient populationdata -Scientific point of-Scientific point of
-Summary data-Estimatedcontactcontact
describingcompletion date-Description of-Description of
ⁱ^{ki/CRS-RL32832}achievement of-Study sponsorpatient populationpatient population
^g/wprimary andand funding-Summary of-Summary of
^s^.orsecondarysourceaggregate dataaggregate data
^le^akendpoints,-Primary,assessing primaryassessing primary
assessment ofsecondaryand secondaryand secondary
^://wikisecondaryoutcome measuresendpoints, safetyendpoints, safety
^h^ttpendpoints, safety-Date outcomeinformationinformation
informationmeasures assessed-Information about-Information about
-Information about-Dates, details ofsubjects quit trialsubjects quit trial
subjects who quitoutcome revisions-Restrictions on-Restrictions on
trial -Actual non-employees’ non-employees’
-Restrictions oncompletion date,discussion ordiscussion or
non-employees’reason forpublication ofpublication of
discussion ordifference fromresults.results.
publication ofestimate-Link to peer-Link to peer
results-If terminated,reviewedreviewed
-Link to peerreason forpublicationspublications
reviewedtermination-completion date-completion date
publications-Results summary-FDA adverse-FDA adverse
-completion datewith trial design,regulatory actionregulatory action

CRS-28
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
-FDA adversemethodology,NONTECHNICANONTECHNI-
regulatory actionoutcomeL REPORT:CAL REPORT:
NONTECHNI-measures,-Point of contact-Point of contact
CAL SUMMARY:summary data-General-General
-Point of contacttables, statisticaldescription ofdescription of
-Generalsignificance ofresults, trial designresults, trial design
description ofresultschanges, andchanges, and
results, trial design-Safety data,reasons forreasons for
changes, andincluding adversechangeschanges
reasons for changesevent informationBOTHBOTH
BOTH -Peer-r eviewed REP O RTS: REP O RTS:
ⁱ^{ki/CRS-RL32832}REPORTS:publications-Trial purpose-Trial purpose
^g/w-Trial purpose-Description of-Trial sponsor-Trial sponsor
^s^.or-Trial sponsorresults review-General-General
^le^ak-Generalprocess, protocoldescription ofdescription of
description of-Status of FDAresults, trial designresults, trial design
^://wikiresults, trial designapplication orchanges, andchanges, and
^h^ttpchanges, andreason trial notreasons forreasons for
reasons for changessubmitted to FDAchangeschanges
[NIH Director to
include links to
Medline citations,
NLM database
product labels,
prior databank
entries.]
Enf orcement REGI STRY : REGI STRY : BOTH: BOTH: BOTH: BOTH:
and CorrectionsNone specified.-RP ensures-RP ensures-Sponsors of FDA-RP ensures-RP ensures
General mechanismssubmissions notsubmissions notnew drugsubmissions notsubmissions not
for enforcingfalse or misleading.false or misleading.applicationsfalse orfalse or

CRS-29
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
compliance with-No federal agency-No federal agencysubmit tomisleading.misleading.
FDA requirementsmay releasemay releaseSecretary-No federal-No federal
may be applicable,research grantresearch grantcertification ofagency mayagency may
but have not beenfunds tofunds tocompliance withrelease grant fundsrelease research
applied by FDA.noncompliant RPs.noncompliant RPs.FFDCA. If not,to noncompliantgrant funds to
-For applicable-Secretary consultsafter hearing,RPs. noncompliant RPs.
trials funded bywith other federalSecretary imposes-FDA-For applicable
FDA, NIH, AHRQ,agencies to$10,000/day civilCommissionertrials funded by
or VA, progressdetermine whethermonetary penaltyverifies requiredFDA, NIH,
report formsstudies funded byuntil certificationsubmissions wereAHRQ, or VA,
includethem andsubmitted. Ifmade whenprogress report
ⁱ^{ki/CRS-RL32832}certification ofconducted under 45information isconsideringforms include
^g/wcompliance. CFR 46 [re federalinaccurate andapplications forcertification of
^s^.orAgency headsprotections forsponsor knew orinvestigationalcompliance.
^le^akverify compliancehuman subjects] areshould havedrug exemptions,Agency heads
before releasingapplicable clinicalknown, afternew drugverify compliance
^://wikigrant funds to RPs.trials, and tonotice andapprovals,before releasing
^h^ttpSecretary consultsdevelop procedureshearing, Secretarybiologics licences. grant funds to
with other federalto ensure resultsorders sponsor toAfter notice to RP,RPs. Secretary
agencies tosubmission.pay civil monetaryopportunity toconsults with
determine whether-NIH Directorpenalty ofcorrect, Secretaryother federal
studies funded bychecks registry to$100,000 torefuses to fileagencies to
them andensure$2,000,000 for anyapplication.determine whether
conducted under 45corresponding30-day period.-Secretary checksstudies funded by
CFR 46 [re federalresults are filed. -To be eligible forregistry to ensurethem and
protections forAfter notice to RP,a federal grant,correspondingconducted under
human subjects]opportunity tocontract, orresults are filed. 45 CFR 46 [re
merit similarcorrect, DirectorcooperativeAfter notice to RP,federal protections
procedures.reportsagreement,opportunity tofor human
-Applications ornoncompliance toprincipalcorrect, Secretarysubjects] merit
submissions underfederal agenciesinvestigatorreportssimilar

CRS-30
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
FFDCA sectionsand Office ofcertifies Actnoncompliance toprocedures.
505, 515, 520(m),Human Researchcompliance.federal agencies-NIH Director
351, or 510(k) [reProtections, postsNoncompliance,and Office ofchecks registry to
new drugs,notice ofafter notice, leadsHuman Researchensure
biologics andnoncompliance into ineligibility,Protections, postscorresponding
devices], must haveregistry andposting ofnotice ofresults are filed.
certifications ofdatabase.noncompliancenoncompliance inAfter notice to RP,
compliance. -FDAnotice in database. registry andopportunity to
-Secretary mayCommissioner todatabase. correct, Director
impose FFDCAverify submissions-In trial with-Secretary ensuresreports
penalties forare made for trialsnonfederalcontent is not falsenoncompliance to
ⁱ^{ki/CRS-RL32832}noncompliance. in applicationssupport, Actor misleading andfederal agencies
^g/wunder FFDCAnoncompliancenon-promotionaland Office of
^s^.orsections 505, 505(i)leads to notice,by checking aHuman Research
^le^ak515, 520(g), 351, oropportunity torepresentativeProtections, posts
510(k) [re new orcorrect, hearing,sample. Afternotice of
^://wikiexempt drugs,$10,000/daynotice to RP,noncompliance in
^h^ttpbiologics andpenalty untilopportunity toregistry and
devices]. After 30compliant.correct, Secretarydatabase.
days after notice,may impose-Applications or
failure to correctFFDCA penaltiessubmissions under
leads to Secretary’sFFDCA sections
refusal to file,505, 515, 351, or
approve, or clear510(k) [re new
application.drugs, biologics
-Secretary toand devices], must
review documentshave certifications
to ensure they areof compliance.
non-promotional,-Secretary may
not false orimpose FFDCA
misleading. 30penalties for

CRS-31
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
days after notice ofnoncompliance,
noncompliance,including civil
penalties maymonetary penalties
apply. ($10,000/day for
-Secretary mayfirst violation,
impose FFDCA$20,000/day for
penalties foreach subsequent
noncompliance,violation) created
including civilby Act.
monetary penalties
created by the Act
ⁱ^{ki/CRS-RL32832}(not more than
^g/w$10,000/day, and
^s^.ornot more than
^le^ak$15,000/ for all
violations of an
^://wikiindividual or
^h^ttp nonprofit
adjudicated in a
single proceeding).
RequiredNone.RESULTS:BOTH: Not laterBOTH:RESULTS: None required by
Studies orThe NIH Directorthan 1 year afterNot later than 1Not earlier than 2clinical trials title.

Reportsconducts a study toenactment,year afteryears after results
determine the best,Comptrollerenactment,database
validated methodsGeneral submits aSecretary submitsestablished,
of making trialreport to Congressto appropriateComptroller
results public afteron a study tocommittees ofGeneral initiates a
the approval of adetermine whetherCongress a reportGAO study of
drug that is theinformation in theon the status of theinclusion of
subject of anregistry andimplementation ofcertain premarket

CRS-32
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
applicable drugdatabase isAct requirementstrials: burden to
trial. Directorconsideredincluding numbersponsors and
submits findings topromotional and toand types of trialsagencies, benefit
the HHS Secretaryevaluate thesubmitted.to patients and
within 18 monthsimplementation ofREGISTRY:health providers,
of initiating thethe database. Secretaryrecommendations.
study.contracts withMakes report to
IOM to conduct aHELP, Energy and
study of the extentCommerce.
to which data
submitted to the
ⁱ^{ki/CRS-RL32832}registry and
^g/wdatabase have
^s^.orimpacted the
^le^akpublic health. Not
later than 6
^://wikimonths after the
^h^ttpcontract date, IOM
submits study to
Secretary
AuthorizedREGISTRY: BOTH:BOTH:BOTH: BOTH:BOTH:
AppropriationsSuch sums as may be$10,000,000 each$10,000,000 eachSuch sums as may$10,000,000 each$10,000,000 each
necessary; FeesFYFYbe necessaryFYFY

collected under
section 21 USC 379h
[re FDA prescription
drug user fees] may
not be used for the
registry.

CRS-33
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
PreemptionNone.BOTH: BOTH:None.BOTH:BOTH:
Yes. No state orYes. No state orYes. No state orYes. No state or
political political political political
subdivision of asubdivision of asubdivision of asubdivision of a
state may require orstate may require orstate may requirestate may require
effect registrationeffect registrationor effector effect
of trials or results.of trials or results.registration ofregistration of
trials or results.trials or results.
Safe HarborNone.BOTH:BOTH:None.BOTH:BOTH:
Somewhat.Somewhat. Somewhat. Somewhat.
ⁱ^{ki/CRS-RL32832}Compliantsubmissions shallCompliantsubmissions shallCompliantsubmissions shallCompliantsubmissions shall
^g/wnot be considerednot be considerednot be considerednot be considered
^s^.or(1) by Secretary as(1) by Secretary as(1) by Secretary as(1) by Secretary as
^le^akevidence of a newevidence of a newevidence of a newevidence of a new
^://wikiintended useintended useintended useintended use
^h^ttpdifferent fromdifferent fromdifferent fromdifferent from
labeling, or (2) aslabeling, or (2) aslabeling, or (2) aslabeling, or (2) as
FFDCA labeling,FFDCA labeling,FFDCA labeling,FFDCA labeling,
adulteration, oradulteration, oradulteration, oradulteration, or
mi sbranding. mi sbranding. mi sbranding. mi sbranding.
Effective DatesREGISTRY: REGISTRY: BOTH:Not specified.BOTH:BOTH:
Currently operational-Generally:-DatabasesDatabases to be-Databases
October 1, 2007established notestablished notestablished not
-Regulationslater than 1 yearlater than 1 yearlater than 1 year
become effectiveafter enactment.after enactment.after enactment.

90 days after
issuance of HHS
Secretary’ s
issuance of final

CRS-34
Current LawS. 1082H.R. 2900 S. 467S. 484H.R. 1561
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
ⁱ^{ki/CRS-RL32832}after regulations’
^g/weffective date.

^s^.or
^le^ak
^://wiki
^h^ttp

Appendix A. World Health Organization,
International Clinical Trials Registry Platform,
Registration Data Set (Version 1.0)
ITEMDEFINITION / EXPLANATION
^Prim^ary^Nam^e^of^P^r^im^ary^R^e^gⁱ^s^t^{er, an}^{d th}^{e u}ⁿⁱ^qu^{e ID n}^u^m^{ber as}^sⁱ^gⁿ^e^{d by}^th^{e P}^r^im^ary
^R^e^gi^s^t^{er an}^d^Regⁱ^ster^to^th^{is tr}^ial.
^Tria^{l ID #}
^Da^{te o}^f^{Date w}^h^en^{trial w}^a^{s o}^f^fⁱ^cially^regⁱ^steredⁱⁿ^th^{e P}^r^im^ary^R^e^gⁱ^{ster YYYY/MM/DD.}
^R^e^gi^s^t^rati^onⁱⁿ
^Prim^ary
^Regⁱ^ster
^{Secondary I}^D^#s^Oth^e^r^id^en^tif^yⁱⁿ^gⁿ^u^m^b^e^r^s^an^d^issuⁱⁿ^g^au^th^o^r^{ities b}^e^sid^e^{s th}^{e P}^r^im^ar^y^Regⁱ^ster^{, if}
^an^y^.^In^cl^u^d^{e t}^h^{e s}^pon^s^o^{r n}^a^m^e^an^{d s}^pon^s^o^r-ⁱ^s^s^u^{ed t}^rⁱ^a^lⁿ^u^m^{ber (e.g}^{., prot}^ocol
ⁿ^u^m^{ber) if}^av^{ailable. A}^l^s^oⁱⁿ^clu^d^{e oth}^e^{r trial reg}ⁱ^s^t^ers^th^{at h}^a^v^e^is^s^u^{ed an}^ID
ⁿ^u^m^b^e^r^to^th^{is tr}^{ial. T}^h^er^{e is n}^o^lim^{it o}ⁿ^th^{e n}^u^m^b^e^r^o^f^Secoⁿ^d^ar^y^I^Dⁿ^u^m^b^e^r^s^th^at
^can^{be prov}ⁱ^d^ed.
^Source(s⁾^of^Maj^o^{r s}^o^u^r^ce(s⁾^of^m^oⁿ^e^t^a^ry^{or m}^a^t^e^ri^al^s^u^pport^f^o^{r t}^h^{e t}^rⁱ^a^l^(e.g^{., f}^uⁿ^dⁱⁿ^g^ag^en^cy^,
^Moⁿ^e^t^a^r^y^o^r^fo^und^a^tⁱ^o^n,^c^o^m^p^aⁿ^y⁾^.
^M^a^terial
^Suppo^rt
^Prim^ary^T^h^{e in}^dⁱ^vⁱ^d^u^{al, o}^r^g^aⁿⁱ^zatioⁿ^,^g^r^o^u^p^o^r^o^t^h^e^r^leg^a^{l p}^e^r^s^oⁿ^takⁱⁿ^g^r^e^sp^oⁿ^sib^ility^f^o^r
^Spo^nso^r^secu^rⁱⁿ^g^th^{e ar}^r^aⁿ^g^e^m^eⁿ^t^{s to}ⁱⁿ^{itiate an}^d^/^o^r^m^aⁿ^a^g^e^{a stu}^d^y⁽ⁱⁿ^c^lu^dⁱⁿ^g^ar^r^aⁿ^g^e^m^eⁿ^t^s
^{to en}^s^u^{re th}^{at th}^{e s}^t^u^d^y^desⁱ^gⁿ^m^eets^{appropriate s}^t^an^dards^an^{d to en}^s^u^re
^ap^p^r^o^p^r^{iate co}ⁿ^d^u^c^{t an}^d^r^e^p^o^r^tin^g⁾^{. I}ⁿ^co^m^m^e^r^c^{ial tr}^{ials, th}^{e p}^r^im^ar^y^sp^oⁿ^so^r^is
ⁿ^o^r^m^ally^th^{e m}^aⁱⁿ^ap^p^lican^{t f}^o^r^r^e^g^u^l^ato^r^y^au^th^o^r^izatioⁿ^to^b^e^gⁱⁿ^th^{e stu}^d^y^.^I^t^m^a^y
^o^r^m^a^yⁿ^o^{t b}^e^th^{e m}^aⁱⁿ^f^uⁿ^d^er^.
^Secondary^A^d^d^itioⁿ^a^{l in}^dⁱ^vⁱ^d^u^{als, o}^r^g^aⁿⁱ^zatioⁿ^s^o^r^o^t^h^e^r^leg^a^{l p}^e^r^s^oⁿ^{s, if}^an^y^,^th^{at h}^a^v^e^ag^r^eed
^Spo^nso^r⁽^s⁾^w^ith^th^{e p}^r^im^ar^y^sp^oⁿ^so^r^to^tak^e^oⁿ^r^e^sp^oⁿ^sib^{ilities o}^f^sp^oⁿ^so^r^s^hⁱ^p^.
^A^s^econ^d^ary^s^pon^s^o^{r m}^a^y^h^a^v^e^ag^reed
^-^t^o^tak^e^oⁿ^{all th}^{e r}^e^sp^oⁿ^sib^{ilities o}^f^sp^oⁿ^so^r^s^hⁱ^p^j^oⁱⁿ^tly^w^ith^th^{e p}^r^im^ar^y^sp^oⁿ^so^r^;
^or
^-^t^o^f^o^r^m^{a g}^r^o^u^p^w^ith^th^{e p}^r^im^ar^y^sp^oⁿ^so^rⁱⁿ^w^h^ich^th^{e r}^e^sp^oⁿ^sib^{ilities o}^f
^s^pon^s^o^rs^hⁱ^{p are allocated am}^on^g^th^{e m}^e^m^b^ers^of^th^{e g}^r^ou^{p; or}
^-^t^o^{act as th}^{e sp}^oⁿ^so^r^’^{s leg}^a^{l r}^e^p^r^esen^tativ^{e in}^r^e^latioⁿ^to^so^m^e^o^r^{all o}^f^th^{e tr}^ial
^{sites; o}^r
^-^t^o^tak^e^resp^oⁿ^sib^ility^f^o^{r th}^{e accu}^racy^o^f^{trial reg}ⁱ^stratioⁿⁱⁿ^f^o^rm^atioⁿ^su^b^m^itted^.
^Con^t^{act for}^Em^{ail ad}^d^r^{ess, telep}^h^oⁿ^{e n}^u^m^b^e^r^,^o^r^p^o^s^{tal ad}^d^r^{ess o}^f^th^{e co}ⁿ^t^{act w}^h^o^w^{ill r}^e^sp^oⁿ^d
^{Public Q}^u^eries^to^g^eⁿ^e^r^a^{l q}^u^er^{ies, in}^clu^dⁱⁿ^gⁱⁿ^f^o^r^m^atioⁿ^ab^o^u^{t cu}^r^r^en^{t r}^ecr^u^itm^en^{t statu}^s
^Con^t^{act for}^Em^{ail ad}^d^r^{ess, telep}^h^oⁿ^{e n}^u^m^b^e^r^,^o^r^p^o^s^{tal ad}^d^r^{ess, an}^d^af^f^iliatioⁿ^o^f^th^{e p}^e^r^s^oⁿ^to
^Scient^if^ic^coⁿ^t^{act f}^o^r^scien^tif^{ic q}^u^er^{ies ab}^o^u^{t th}^{e tr}^{ial (}^e^.g^{., p}^rⁱⁿ^cip^a^{l in}^v^e^stig^ato^r^{, m}^e^dⁱ^cal
^Q^u^eries^dⁱ^r^ecto^r^em^p^l^o^y^ed^b^y^th^{e sp}^oⁿ^so^r⁾^{. Fo}^r^{a m}^u^lti-^cen^ter^stu^d^y^,^en^ter^th^{e co}ⁿ^t^act
ⁱⁿ^f^o^r^m^atioⁿ^f^o^r^th^{e lead}^P^rⁱⁿ^cip^a^{l I}ⁿ^v^e^stig^ato^r^o^r^o^v^er^{all scien}^tif^{ic d}ⁱ^r^ecto^r^.
^{Public Tit}^l^e^Em^{ail ad}^d^r^{ess, telep}^h^oⁿ^{e n}^u^m^b^e^r^,^o^r^p^o^s^{tal ad}^d^r^{ess, an}^d^af^f^iliatioⁿ^o^f^th^{e p}^e^r^s^oⁿ^to
^coⁿ^t^{act f}^o^r^scien^tif^{ic q}^u^er^{ies ab}^o^u^{t th}^{e tr}^{ial (}^e^.g^{., p}^rⁱⁿ^cip^a^{l in}^v^e^stig^ato^r^{, m}^e^dⁱ^cal
^dⁱ^r^ecto^r^em^p^l^o^y^ed^b^y^th^{e sp}^oⁿ^so^r⁾^{. Fo}^r^{a m}^u^lti-^cen^ter^stu^d^y^,^en^ter^th^{e co}ⁿ^t^act
ⁱⁿ^f^o^r^m^atioⁿ^f^o^r^th^{e lead}^P^rⁱⁿ^cip^a^{l I}ⁿ^v^e^stig^ato^r^o^r^o^v^er^{all scien}^tif^{ic d}ⁱ^r^ecto^r^.

^Scient^if^{ic Tit}^l^e^Scien^tif^{ic title o}^f^th^{e stu}^d^y^{as it ap}^p^ear^{s in}^th^{e p}^r^o^t^o^c^o^l^su^b^m^itted^f^o^r^f^uⁿ^dⁱⁿ^g^an^d
^ethⁱ^{cal rev}ⁱ^ew^{. In}^clu^d^{e trial acron}^y^m^if^av^ailable.
^Countries^of^T^h^{e co}^uⁿ^t^rⁱ^{es f}^r^o^m^w^h^ich^p^a^r^ticip^an^{ts w}^{ill b}^e^{, ar}^{e in}^ten^d^ed^to^b^e^{, o}^r^h^a^v^e^b^een
^Recruitm^e^nt^recru^ited.
^Heal^th^P^r^im^ar^y^h^ealth^coⁿ^d^itioⁿ⁽^s)^o^r^p^r^o^b^l^em⁽^s⁾^stu^d^ied⁽^e^.g^{., d}^e^p^r^essioⁿ^{, b}^r^{east can}^cer^,
^Con^dⁱ^ti^on^(s^{) or}^m^e^dⁱ^c^a^tⁱ^o^{n e}^r^r^o^r⁾^.^I^f^t^h^e^st^ud^yⁱ^s^c^o^nd^uc^t^e^d^oⁿ^he^a^l^t^h^y^hum^aⁿ^vo^l^unt^e^e^r^{s b}^e^l^o^ngi^ng
^Prob^lem⁽^s⁾^t^o^t^h^{e t}^a^rg^et^popu^l^a^tⁱ^oⁿ^of^t^h^{e i}ⁿ^t^e^rv^en^tⁱ^oⁿ^(e.g^{., prev}^en^t^a^tⁱ^v^{e or s}^c^reenⁱⁿ^g
^St^udiedⁱⁿ^ter^v^en^tioⁿ^s⁾^,^en^ter^th^{e p}^a^r^ticu^l^ar^h^ealth^coⁿ^d^itioⁿ⁽^s)^o^r^p^r^o^b^l^em⁽^s⁾^b^eⁱⁿ^g
^p^r^e^v^eⁿ^t^e^d^.^I^f^t^h^e^st^ud^yⁱ^s^c^o^nd^uc^t^e^d^usi^{ng he}^a^l^t^h^y^hum^aⁿ^vo^l^unt^e^e^r^{s no}^t^b^e^l^o^ngi^ng
^t^o^t^h^{e t}^a^rg^et^popu^l^a^tⁱ^oⁿ^(e.g^{., a prel}ⁱ^mⁱⁿ^ary^s^a^f^e^t^y^s^t^u^d^y⁾^{, an}^appropri^a^t^e^k^e^y^w^ord
^w^{ill b}^e^d^e^fⁱⁿ^e^d^f^o^r^u^s^er^{s to}^select.
^Iⁿ^tervention(s⁾^En^{ter th}^{e s}^p^ecifⁱ^{c n}^a^m^e^of^th^{e in}^terv^en^tion⁽^s⁾^an^{d th}^{e com}^p^arator/con^trol(s^{) bein}^g
^stu^d^ied^.^{Use th}^{e I}ⁿ^terⁿ^atioⁿ^a^{l No}ⁿ^-^P^r^o^p^r^ietar^y^Nam^e^if^p^o^ssib^l^{e (}ⁿ^o^t^b^r^an^d^/tr^ad^e
ⁿ^a^m^e^s⁾^{. For an}^uⁿ^r^eg^is^{tered dru}^g^,^th^{e g}^eⁿ^e^{ric n}^a^m^e^{, ch}^em^{ical n}^a^m^e^{, or com}^p^an^y
^s^e^{rial n}^u^m^{ber is}^{acceptable. If}^th^{e in}^terv^en^tion^con^s^is^ts^of^s^e^v^e^{ral s}^e^parate
^tr^eatm^eⁿ^t^{s, list th}^em^{all in}^oⁿ^{e lin}^{e sep}^a^r^a^ted^b^y^co^m^m^a^{s (}^e^.g^{., “}^l^o^w^-^f^a^{t d}ⁱ^et,
^ex^ercis^e”).
^T^h^{e co}ⁿ^t^r^o^{l in}^ter^v^en^tioⁿ⁽^s)^is/ar^e^th^{e in}^ter^v^en^tioⁿ^s^ag^ain^s^{t w}^h^ich^th^{e stu}^d^y
ⁱⁿ^terv^en^tion^is^ev^alu^a^{ted (e.g}^{., placebo, n}^o^treatm^eⁿ^t^{, activ}^{e con}^t^{rol). If}^an^activ^e
^coⁿ^t^r^o^{l is u}^s^ed^{, b}^e^su^r^e^to^en^terⁱⁿ^th^{e n}^a^m^e⁽^s⁾^o^f^th^{at in}^ter^v^en^tioⁿ^,^o^r^en^ter
^“^p^{lacebo” or “}ⁿ^{o treatm}^eⁿ^t^{” as}^applicable.
^{For each}ⁱⁿ^terv^en^tion^,^des^c^{ribe oth}^e^{r in}^terv^en^tion^details^as^{applicable (dos}^e,
^du^ratⁱ^oⁿ^,^m^{ode of}^admⁱⁿⁱ^s^t^ratⁱ^oⁿ^,^et^c).
^{Key I}ⁿ^cl^u^sⁱ^oⁿ^In^clu^s^ion^an^{d ex}^clu^s^ion^{criteria f}^o^{r partic}^ipan^{t s}^e^lection^,ⁱⁿ^clu^dⁱⁿ^g^ag^{e an}^{d s}^e^x^.
^a^{nd Exclusio}ⁿ
^Criteria
^St^udy^Ty^pe^A^sin^g^l^{e ar}^m^stu^d^y^{is o}ⁿ^{e in}^w^h^ich^{all p}^a^r^ticip^an^{ts ar}^{e g}ⁱ^v^eⁿ^th^{e sam}^eⁱⁿ^ter^v^en^tioⁿ^.
^T^r^ialsⁱⁿ^w^h^ich^participan^ts^{are as}^sⁱ^gⁿ^e^{d to receiv}^e^on^{e of}^tw^{o or m}^o^{re in}^terv^en^tion^s
^{are NOT}^sⁱⁿ^g^l^{e arm}^s^t^u^d^ies^.^C^r^os^s^o^v^e^{r trials}^{are NOT}^sⁱⁿ^g^l^{e arm}^s^t^u^d^ies^.
^A^tr^{ial is “}^r^an^d^o^m^ized^{” if}^p^a^r^ticip^an^{ts ar}^{e assig}ⁿ^e^d^toⁱⁿ^ter^v^en^tioⁿ^g^r^o^u^p^s^u^sⁱⁿ^g^a
^m^e^th^{od bas}^e^{d on}^ch^an^{ce (e.g}^{., ran}^domⁿ^u^m^{ber table, ran}^dom^com^p^u^t^er-^g^en^erated
^s^e^qu^en^{ce, m}ⁱⁿⁱ^mⁱ^zation^,^adaptiv^{e ran}^dom^ization⁾^.
^Da^{te o}^f^First^Aⁿ^ticip^ated^o^r^actu^a^{l d}^a^{te o}^f^en^ro^llm^en^{t o}^f^th^{e f}ⁱ^{rst p}^a^rticip^an^{t (YYYY/MM).}
^Eⁿ^rollm^ent
^T^a^{rget Sam}^p^le^Nu^m^b^er^o^f^p^a^r^ticip^an^{ts th}^{at th}^{is tr}^{ial p}^l^an^{s to}^en^r^o^ll.
^Size
^Recruitm^e^nt^Recr^u^itm^en^{t statu}^s^o^f^th^{is tr}^ial.
^St^a^t^us^-^P^en^dⁱⁿ^g^:^p^a^r^ticip^an^{ts ar}^{e n}^o^{t y}^e^{t b}^eⁱⁿ^g^r^ecr^u^ited^o^r^en^r^o^lled^{at an}^y^site
^-^A^ctiv^{e: participan}^ts^{are cu}^rren^tly^bein^g^recru^{ited an}^{d en}^rolled
^-^T^em^p^o^r^ar^y^h^a^{lt: th}^er^{e is a tem}^p^o^r^ar^y^h^a^{lt in}^r^ecr^u^itm^en^{t an}^d^en^r^o^llm^en^t
^-^C^lo^sed^:^p^a^r^ticip^an^{ts ar}^{e n}^o^loⁿ^g^e^r^b^eⁱⁿ^g^r^ecr^u^ited^o^r^en^r^o^lled
^Prim^ary^Ou^tcom^es^{are ev}^en^ts^{, v}^a^riables^,^{or ex}^perien^ces^th^{at are m}^eas^u^r^{ed becau}^s^e^{it is}
^Ou^tcom^e(s⁾^b^e^liev^e^d^th^{at th}^ey^m^a^y^b^eⁱⁿ^f^l^u^eⁿ^ced^b^y^th^{e in}^ter^v^en^tioⁿ^.^T^h^{e P}^r^im^ar^y^Ou^tco^m^e
^sh^o^u^ld^b^e^th^{e o}^u^tco^m^{e u}^s^edⁱⁿ^sam^p^{le size calcu}^latioⁿ^s^{, o}^r^th^{e m}^aⁱⁿ^o^u^tco^m^e(^s)
^u^s^ed^to^d^e^ter^mⁱⁿ^{e th}^{e ef}^f^{ects o}^f^th^{e in}^t[^er^v^eⁿ^tioⁿ⁽^s)^.
^En^ter^th^{e n}^a^m^e^{s o}^f^{all p}^r^im^ar^y^o^u^tco^m^{es in}^th^{e tr}^{ial as w}^e^{ll as th}^{e p}^r^e-^sp^ecifⁱ^ed
^tim^ep^oⁱⁿ^t⁽^s⁾^o^f^p^r^im^ar^yⁱⁿ^ter^e^{st. B}^e^{as sp}^ecifⁱ^{c as p}^o^ssib^l^{e w}^ith^th^{e m}^e^tr^{ic u}^s^ed
^(e.g^{., “}^%^w^ith^B^eck^Depres^sⁱ^on^{Score > 10” rath}^{er th}^an^j^u^s^t^“^d^epres^sⁱ^on^”).
^Ex^am^ples^:
^Ou^tco^m^{e Nam}^e^{: all-}^cau^{se m}^o^r^t^ality^{, T}ⁱ^m^e^p^oⁱⁿ^t^{s: 5}^y^ear^{s; o}^r^Ou^tco^m^{e Nam}^e^{: Mean}
^Beck^D^e^pres^sⁱ^on^S^c^{ore, T}ⁱ^m^e^poiⁿ^t^:^{18 w}^eek^s

^Secondary^Secon^d^ary^ou^tcom^es^{are ev}^en^ts^{, v}^a^riables^,^{or ex}^perien^ces^th^{at are of}^s^econ^d^ary
^Ou^tcom^e(s⁾ⁱⁿ^teres^t^{or th}^{at are m}^eas^u^r^{ed at tim}^epoiⁿ^t^s^of^s^econ^d^aryⁱⁿ^teres^t^{. A}^s^econ^d^ary
^ou^tcom^{e m}^a^yⁱⁿ^v^o^lv^{e th}^{e s}^a^m^e^ev^en^{t, v}^a^{riable, or ex}^perien^{ce as}^th^{e prim}^ary
^ou^t^c^om^{e, bu}^t^m^eas^u^r^{ed at}^tⁱ^m^epoiⁿ^t^s^ot^h^e^{r t}^h^an^t^h^os^{e of}^pri^m^aryⁱⁿ^t^e^res^t^(e.g^.,
^P^r^im^ar^y^o^u^tco^m^{e: all-}^cau^{se m}^o^r^t^ality^{at 5}^y^ear^{s; Seco}ⁿ^d^ar^y^o^u^tco^m^{e: all-}^cau^se
^m^o^r^t^ality^{at 1}^y^ear^{, 3}^y^ear^s)^{, o}^r^m^a^yⁱⁿ^v^o^lv^{e a d}ⁱ^f^f^e^r^eⁿ^t^ev^en^{t, v}^a^rⁱ^ab^{le, o}^r
^ex^p^e^rⁱ^en^{ce alto}^g^e^th^er⁽^e^.g^{., P}^r^im^ar^y^o^u^tco^m^{e: all-}^cau^{se m}^o^r^t^ality^{at 5}^y^ear^s;
^Secon^d^ary^ou^tcom^{e: h}^o^s^p^italization^{rate at 5 y}^ears⁾^.
^En^{ter th}^{e n}^a^m^e^an^{d tim}^epoin^t^(s^{) f}^o^{r all s}^econ^d^ary^ou^tcom^es^of^clin^{ical an}^d/or
^scien^tif^{ic im}^p^o^r^tan^{ce. B}^e^{as sp}^ecifⁱ^{c as p}^o^ssib^l^{e w}^ith^th^{e m}^e^tr^{ic u}^s^ed⁽^e^.g^{., “}^%^w^ith
^B^eck^Depres^sⁱ^on^{Score > 10” rath}^{er th}^an^j^u^s^t^“^d^epres^sⁱ^on^{”). Ex}^am^ples^{: Ou}^tcom^e
^Nam^e^{: all-}^cau^{se m}^o^r^t^ality^{, T}ⁱ^m^e^p^oⁱⁿ^t^{s: 6}^m^oⁿ^t^h^s^{, 1}^y^ear^{; o}^r^Ou^tco^m^{e Nam}^e^{: Mean}
^g^l^y^c^os^y^l^at^{ed h}^e^m^o^g^l^obiⁿ^A¹^C^,^Tⁱ^m^e^poiⁿ^t^s^:^{4 an}^{d 8 w}^eek^s
^Source:^W^{HO, IC}^T^R^P^,^“^R^eg^is^tration^{Data Set (v}^ersⁱ^on^1.0),”^(March^16,^2007),^{at [h}^ttp://^www.^wh^o^.
ⁱⁿ^{t/ictrp/data_s}^et/en^/^{], v}ⁱ^s^{ited A}^p^{r. 16, 2007.}