Clinical Trials Reporting and Publication

Congressional research reportJul 12, 2007

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Order Code RL32832

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

[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 110th 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 110th 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 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 postmarket 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

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.

“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

Robert Steinbrook, “Public Registration of Clinical Trials,” JAMA, vol. 351, no. 4 (July

22, 2004), p. 315.

Robert Steinbrook, “Gag Clauses in Clinical-Trial Agreements,” New England Journal of

Medicine, vol. 352, no. 21 (May 26, 2005), p. 2160.

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.

For further information on the role of federal agencies in evaluating biomedical products,

(continued...)

CRS-3

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

(...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.

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].

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].

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...)

CRS-4

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

(...continued)

accompany H.R. 5006, 108th Cong., 2nd sess., H.Rept. 108-636 (Washington, GPO, 2004).

Pursuant to 21 U.S.C. § 355(i).

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)).

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].

Shankar Vedantam, “Drugmakers Prefer Silence on Test Data,” Washington Post, July 6,

(continued...)

CRS-5

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

(...continued)

2004, p. A1.

“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].

“FDA to Stop Tracking Industry Compliance With Clinical Trial Registry,” Inside

Washington Publishers, September 26, 2006.

“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].

“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].

CRS-6

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

“International Clinical Trials Registry Platform” World Health Organization website, May

19, 2006, [http://www.who.int/ictrp/en/].

“PhRMA Opposes UN Plan for Trial Data Disclosure,” Inside Washington Publishers,

May 30, 2006.

“AdvaMed, WHO at Odds Over Global Trial Registry Standards,” Inside Washington

Publishers, July 19, 2006.

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].

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].

CRS-7

[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

participants presented a range of views on the need for registries, registry content,

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].

American Medical Association, “610. Physicians and Clinical Trials,” December 2004

Resolutions, at [http://www.ama-assn.org/meetings/public/interim04/resolutions.pdf].

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/print/13909.html].

“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].

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].

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].

CRS-8

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

Legislation

A number of bills related to clinical trials reporting and publication have been

introduced in the 110th Congress.

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].

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

[http://www.ifpma.org/News/NewsReleaseDetail.aspx?nID=2205].

IFPMA, “IFPMA Improves Biomedical Data Transparency with Launch of First

Worldwide Clinical Trials Portal,” IFPMA Press Release, September 21, 2005, at

[http://www.ifpma.org/clinicaltrials.html].

CRS-9

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 110th Congress 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).

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

CRS-10

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.

CRS-11

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 industry

consensus.32 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

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

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

CRS-13

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 110th Congress

Title

Sponsor

Current Law

S. 1082

H.R. 2900

Data bank of

information on

clinical trials for

drugs for serious or

life-threatening

diseases and

conditions

Food and Drug

Administration

Revitalization Act

Food and Drug

Administration

Amendments Act

of 2007

FACT Act

Food and Drug

Enhancing Drug

Administration

Safety and

Revitalization Act Innovation Act of

2007

Senator Kennedy

Representative

Pallone

Senator Dodd

Senator Enzi

Representative

Waxman

Subsection (i) of

section 402 of

PHSA (42 USC

282 as amended

by PL 109-482).

Subsection (i) of

section 402 of

PHSA (42 USC

282), as amended

by PL 109-482.

Both

Law Amended

(Existing law) PHSA PHSA (42 U.S.C.

(42 U.S.C. § 282 (j)) 282), as amended;

and Section 492

A(a) of the PHSA

Registry and/or

Results

Database

Required

Registry expanded, Both.

Registry only

and includes links

(clinicaltrials.gov);

with sponsor consent, to certain results.

Results database to

registry may also

include information be created by HHS

Secretary

about the results of

rulemaking

registered trials,

S. 467

PHSA Title IV (42 PHSA (42 U.S.C.

U.S.C. 281, et seq.) 282), as amended

by Public Law

109-482; and

Section 492 A(a)

of the PHSA

Both

S. 484

H.R. 1561

CRS-15

Current Law

S. 1082

H.R. 2900

including potential

toxicities or adverse

effects

following

recommendations

to be made in NIH

Director’s report

about best,

validated method of

making trial results

publically

available.

Product Trial

Types Included

REGISTRY:

Drugs

REGISTRY:

Drugs, devices,

biologics

Public Access

REGISTRY:

Yes, via information

systems, which are to

include toll-free

telephone

communications

BOTH:

REGISTRY:

Yes, via Internet. Yes, via Internet.

Yes, via

Yes, via Internet.

FOIA request

Internet posting

information

Internet posting and FOIA request

systems, which are and FOIA request disclosures not

disclosures not

FOIA request

disclosures limited available for results to include toll-free disclosures limited available for

to terms of the act. results for which

telephone

to terms of the act. for which the

the principal

communications. Secretary

principal

Secretary

investigator is

Provisions related promulgates

investigator is

promulgates

seeking

regulations that

to disclosure of

seeking

regulations that

BOTH:

Drugs, devices,

and biologics.

S. 467

S. 484

BOTH:

Drugs, biologics, Drugs, biologics,

eventually

devices.

Information about possibly devices

other trials may be

voluntarily

submitted.

H.R. 1561

BOTH:

Drugs, devices,

biologics

CRS-16

Current Law

S. 1082

H.R. 2900

S. 467

notice of posting be publication.

part of informed

Old versions of

consent.

updated postings

remain available,

with trackable

changes the public

can see.

FDA reviews

supersede FOIA.

S. 484

H.R. 1561

notice of posting publication.

be part of

informed consent.

Location of

Databases

REGISTRY:

NLM at NIH is

current location

REGISTRY:

NLM at NIH

BOTH: NLM and

NIH

REGISTRY:

Either supplants or

builds on

clinicaltrials.gov,

whichever is more

efficient.

BOTH:

NIH.

Not specified, but NIH.

REGISTRY:

bill amends the

Either supplants or Either supplants or

portion of the

builds on

USC related to the builds on

clinicaltrials.gov, clinicaltrials.gov,

current registry,

which is located at whichever is more whichever is more

efficient.

NLM at NIH.

Links Between

Registry,

Results

Database

REGISTRY:

Not specified; except

that the activities of

the data bank are to

be integrated and

coordinated with

related activities of

other agencies of the

DHHS, and, to the

extent practicable,

REGISTRY:

Entries link to

certain existing

results.

BOTH:

Corresponding

registry and results

database entries

link to one another.

REGISTRY:

Not specified,

Entries link to

except that the

results entries.

Secretary shall

assign each

clinical trial a

unique identifier

to be included in

the registry and in

the database.

BOTH:

Corresponding

registry and

results database

entries link to one

another.

CRS-17

Current Law

S. 1082

H.R. 2900

S. 467

S. 484

H.R. 1561

BOTH:

Responsible party

(RP): if such

clinical trial is the

subject of an

investigational

new drug

application or an

application for an

investigational

device exemption

— the sponsor; if

not — the person

that provides the

largest share of

monetary support,

but if that person

is federal or state

agency — the

principal

investigator; if the

main funder is a

nonprofit — the

BOTH:

Responsible party

(RP): sponsor, or

principal

investigator if

designated by

sponsor

BOTH:

Responsible party

(RP): primary

sponsor as defined

by WHO, or

principal

investigator (PI) if

designated by

sponsor and if PI

is responsible for

conducting the

trial, has access to

and control over

data, has the right

to publish trial

results, and has

the responsibility

to meet the RP

responsibilities.

coordinated with

other data banks

containing similar

information.

Who Submits

Information

REGISTRY:

Sponsor

BOTH:

REGISTRY:

Responsible party Responsible party

(RP): sponsor; if no (RP): primary

sponsor as defined

sponsor existsgrantee, contractor by WHO, or

principal

or awardee of

federal funding; if investigator (PI) if

designated by

sponsor and if PI is

sponsor, grantee,

responsible for

contractor or

awardee - principal conducting the

trial, has access to

investigator.

and control over

data, has the right

to publish trial

results, and has the

responsibility to

meet the RP

responsibilities.

CRS-18

Current Law

S. 1082

H.R. 2900

S. 467

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.

S. 484

H.R. 1561

CRS-19

Current Law

S. 1082

H.R. 2900

Who Receives

Information

REGISTRY:

HHS Secretary,

acting through the

NIH Director

REGISTRY:

Director of NIH

BOTH:

Director of NIH

Timing of

Submission

REGISTRY:

Not later than 21

days after the

approval of the

protocol

REGISTRY:

-Initially: not later -Initially: not later

than 21 days after than 14 days after

first patient is

the first patient is

enrolled

enrolled.

-Updates: not less

-Change in

enrollment status: than once every 6

months

not later than 30

days after change. -Change in

Enrollment

-Completion of

trial: not later than Status: not later

than 30 days after

30 days after the

last patient enrolled change

in the clinical trial -Notice of trial

has completed his completion: Not

or her last medical later than 30 days

after final

visit, whether the

collection of data

clinical trial

from subjects for

conducted

primary and

according to the

secondary

prespecified

outcomes

protocol or plan

RESULTS:

was terminated

-Generally: Not

(extensions

later than 1 year

possible).

S. 467

S. 484

H.R. 1561

BOTH:

Director of NIH

HHS Secretary,

acting through the

NIH Director

BOTH:

Director of NIH

REGISTRY:

-Initially: not

later than 21 days later than 14 days

after the trial is

after first patient

opened for

is enrolled

enrollment.

-Change in

RESULTS:

Enrollment

-Initially: implied Status: not later

same date as for

than 30 days after

registry. (To the

change

extent practicable, -Final

the Secretary

Submission: Not

ensures that where later than 30 days

the same

after last enrolled

information is

patient has last

required for the

medical visit

registry and the

RESULTS:

database (such as -Generally: Not

initial information later than 1 year

after last enrolled

required for the

patient has last

database), a

medical visit

process exists to

(extensions

allow the RP to

possible).

make only one

-Changes in

submission.

REGISTRY:

-Initially: not

later than 14 days

after first patient

is enrolled

-Updates: not less

than once every 6

months

-Change in

Enrollment

Status: not later

than 30 days after

change

-Notice of trial

completion: Not

later than 30 days

after final

collection of data

from subjects for

primary and

secondary

outcomes

RESULTS:

-Generally: Not

later than 1 year

CRS-20

Current Law

S. 1082

H.R. 2900

S. 467

S. 484

H.R. 1561

-Results: not later regulatory status: after earlier of

after earlier of

within 30 days

estimated or actual

estimated or actual than 1 year than

after change

completion date

the earlier of the

completion date

(extensions

trials’ estimated or

(extensions

possible)

actual completion

possible)

-Updates: every 6

-Updates: every 6 date (extensions

months for 10

months for 10 years possible).

years from when

BOTH:

from when initial

initial posting was

-Changes:

posting was

required

within 30 days of

required

-Changes in

the date on which

-Changes in

regulatory status:

regulatory status: the RP or principal

within 30 days

within 30 days after investigator

after change

became aware of

change

the change

Timing of

Posting

REGISTRY:

Not specified

REGISTRY:

-Trials of drugs

and biological

products: within

30 days of

submission

-Trials of devices:

within 30 days of

clearance under

section 510(k) of

the FFDCA or

approval under

sections 515 or

520(m) of the

REGISTRY:

-Not specified

(NIH Director

ensures the registry

information is

made publically

available via

Internet) except

that NIH Director

may not make

registry

information about

device trials public

until the device is

REGISTRY:

BOTH:

In making

-Not specified

information about (NIH Director

clinical trials

ensures the

publicly available, registry

the Secretary shall information is

make information made publically

available as soon available via

as practicable after Internet)

receiving the data, RESULTS:

and shall seek to (delays of up to 2

be as timely and

years possible if

transparent as

seeking

possible.

publication)

REGISTRY:

-Not specified

(NIH Director

ensures the

registry

information is

made publically

available via

Internet)

RESULTS:

(delays of up to 2

years possible if

seeking

publication)

CRS-21

Current Law

S. 1082

H.R. 2900

S. 467

approved or cleared (Postponement

FFDCA

and extensions for

by FDA.

-Links to trial

results (from FDA RESULTS: (delays publication are

possible).

of up to 2 years

and NIH

information) that possible if seeking

form the basis of publication)

an efficacy claim -Pre-approval

or are conducted studies: not later

after the drug or than 30 days after

approval or

biologic is

issuance of not

approved or the

approvable letter

device is cleared

or approved: not -Summaries of

earlier than 30 days medical, clinical

pharmacology

after the date of

reviews of preapproval or

clearance, not later approval and new

than 30 days after use studies: within

90 days of

the produce

becomes publically applicable date

-Post-approval

available.

studies generally:

within 30 days of

submission

-Post-approval

studies of new

uses in which

manufacturer is a

trial sponsor and

certifies it is

S. 484

H.R. 1561

-Pre-approval

studies: not later studies: not later

than 30 days after than 30 days after

approval or

issuance of not

approvable letter approvable letter

-Post-approval

-Summaries of

studies generally: medical, clinical

not later than 30

pharmacology

days after

reviews of presubmission

approval and

-Post-approval

new use studies:

studies of new

within 90 days of

uses in which the applicable date

manufacturer is a -Post-approval

trial sponsor and studies generally:

certifies it is

within 30 days of

seeking or will

submission

seek approval

-Post-approval

within 1 year: not studies of new

later than 30 days uses in which

after approval,

manufacturer is a

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

CRS-22

Current Law

S. 1082

H.R. 2900

S. 467

S. 484

approvable letter,

or application

withdrawal; or 2

years after

certification.

seeking or will

seek approval

within 1 year: not

later than 30 days

after approval,

issuance of not

approvable letter,

or application

withdrawal; or 2

years after

certification.

Searchable By

REGISTRY:

Not specified (But

for a list of required

data elements, see

that entry below.)

REGISTRY:

-Trial enrollment

-Indication, using

status

Medical Subject

-Trial sponsor

Headers

-Source of support RESULTS:

-Status of FDA

-Study phase

application

-Treatment

-Recruitment status -Trial phase

-Product name

-Age group

(including pediatric -Each financial

sponsor

subpopulations)

BOTH:

-Study location

-National Clinical -Indication, using

Medical Subject

Trial number or

other identification Headers

-Safety issue being

number

studied

H.R. 1561

BOTH:

Not specified (But

for a list of

required data

elements, see that

entry below.)

REGISTRY:

-Enrollment status

-Approval status

RESULTS:

-Each financial

sponsor

-Clinical trial

phase

-Safety issue

-Drug name

BOTH:

-Indication, using

Medical Subject

Headers

-Sponsor

REGISTRY:

-Trial enrollment

status

-Trial sponsor

RESULTS:

-Status of FDA

application

-Trial phase

-Product name

-Each financial

sponsor

BOTH:

-Indication, using

Medical Subject

Headers

-Safety issue

being studied

-Trial sponsor

CRS-23

Current Law

Trials Included

S. 1082

H.R. 2900

BOTH:

REGISTRY:

-Drug, device,

-Investigational new -Device trials:

biologic clinical

prospective study

drug trials: trials

(whether federally or of health outcomes trials: trials testing

a products’ safety

privately funded) of comparing an

intervention against or effectiveness if

experimental

treatments for serious a control in human conducted in the

subjects intended to U.S. or if the

or life- threatening

product has FDA

support an

diseases and

approval or is the

application under

conditions under

section 520 (m) [re subject of an

regulations

application for

promulgated pursuant humanitarian

devices] or 515 [re FDA approval.

to section 21 USC

premarket approval

355(i) [re

of devices] or a

investigational new

report under section

drugs].

510(k) [re device

-Treatment use of

investigational new clearance] of the

FFDCA; pediatric

drugs:

postmarket

information

surveillance as

pertaining to

required under

experimental

treatments for serious section 522 of the

FFDCA (as

or life-threatening

amended by the

diseases and

conditions that may bill).

-Drug and biologic

be available (i) under a treatment trials: a controlled

clinical

investigational new

drug application that investigation of a

has been submitted to product subject to

S. 467

S. 484

H.R. 1561

REGISTRY:

BOTH:

REGISTRY:

- Non-phase I

-Drug, device,

-Premarket:

clinical trials of

biologic clinical

Trials to verify

drugs, devices,

trials: Trials

efficacy and

biologics: trials

testing a products’

establish doses

testing a treatment -Confirmatory:

safety or

for a

effectiveness if

All

life-threatening

conducted in the

RESULTS:

disease or

U.S. or if the

-Premarket:

condition, that are Trials to verify

product has FDA

federally funded, efficacy and

approval or is the

used in requesting establish doses if subject of an

FDA approval,

recommended by a application for

and/or conducted required GAO

FDA approval.

in the United

study and required

States.

by the HHS

RESULTS:

Secretary through

- Non-phase I

rulemaking;

Drug, device, or fast track product

biologic clinical trials if used as the

trials, and those basis for efficacy.

required by the

-Confirmatory:

HHS Secretary in Premarket

confirmatory trials

the interest of

public health: if BOTH:

federally funded, -Postmarket: all.

used in requesting -Pediatric

Pharmacokinetic:

FDA approval,

all

and/or

conducted in the

United States.

CRS-24

Exceptions

(trials not

included)

Current Law

S. 1082

the Secretary under

21 USC 360bbb(c);

(ii) as a Group C

cancer drug (as

defined by the

National Cancer

Institute).

section 505 [re

drug approval] or

351 [re approval of

biological

products] of the

FFDCA.

-Other trials:

voluntary

submissions may

be made.

H.R. 2900

BOTH:

REGISTRY:

-Pharmacokinetic

Information relating -Device trials:

and toxicity

to an investigation if limited studies to

studies: a clinical

gather essential

the sponsor has

information used to trial to determine

provided a detailed

refine the device or the safety of a use

certification to the

of a drug that is

design a pivotal

Secretary that

trial and that is not designed solely to

disclosure would

detect major

substantially interfere intended to

toxicities in the

determine safety

with the timely

and effectiveness of drug or to

enrollment of

investigate

a device.

subjects in the

pharmacokinetics,

investigation, unless -Drug and

unless the clinical

Biologic Trials:

the Secretary, after

trial is designed to

Phase I trials.

the receipt of the

investigate

certification, provides

S. 467

S. 484

H.R. 1561

BOTH:

clinical trial

means a research

study in human

volunteers to

answer specific

health questions,

including

treatment,

prevention,

diagnostic,

screening, and

quality-of-life

trials

BOTH:

-Phase I clinical -Exploratory

trials conducted

trials solely to

solely to test the

assess safety,

safety of an

evaluate

unapproved drug pharmacokinetics,

or unlicensed

or verify efficacy

biological product, -Observational

pilot or feasibility studies

studies conducted

to confirm the

design and

operating

specifications of

an unapproved or

not yet cleared

BOTH:

-Pharmacokinetic

and toxicity

studies: a clinical

trial to determine

the safety of a use

of a drug that is

designed solely to

detect major

toxicities in the

drug or to

investigate

pharmacokinetics,

unless the clinical

trial is designed to

investigate

CRS-25

Current Law

S. 1082

the sponsor with a

detailed written

determination that

such disclosure

would not

substantially interfere

with such enrollment.

Registry Data

Elements

-Purpose of each

experimental drug

-Eligibility criteria

-Location of trial

sites

-Point of contact for

enrollment

-Description of

whether and how the

manufacturer or

sponsor will respond

to requests for

protocol exception,

with appropriate

safeguards, for

single- patient and

-WHO elements

(See Appendix A.)

-City, state, zip

code of study

-Toll free number

for study

-Whether there is

expanded access

for unapproved

drugs and biologics

under FFDCA

section 561 [re

emergency

situations, patient

access to

treatments for

H.R. 2900

S. 467

S. 484

H.R. 1561

pharmacokinetics

in a special

population or

populations; and

-Feasibility

studies: a small

clinical trial to

determine the

feasibility of a

device, or a clinical

trial to test

prototype devices

where the primary

focus is feasibility.

medical device

may be included

with RP consent.

-Clinical trials of

other healthrelated

interventions may

be included with

consent of RP.

pharmacokinetics

in a special

population or

populations; and

-Feasibility

studies: a small

clinical trial to

determine the

feasibility of a

device, or a

clinical trial to test

prototype devices

where the primary

focus is feasibility.

-WHO elements

-Trial title

(See Appendix A.) -Unique identifier

-City, state, zip

-Trial description

code, toll free

-Trial phase

phone number of

-Trial type

study

-Trial purpose

-Estimated

-Primary,

completion date

secondary

-RP identity and

outcome measures

contact information -Date outcome

-Whether there is

measures will be

expanded access

assessed

for unapproved

-Dates and details

drugs and biologics of revisions to

under FFDCA

outcomes

section 561 [re

-Eligibility and

-WHO elements

-Sponsor

(See Appendix

-Trial purpose

A.)

-Patient

-City, state, zip

population

code of study

description

-Estimated

-General

completion date

description of

results, trial design -RP identity and

contact

changes, and

information

reasons for

-Whether there is

changes

expanded access

-WHO elements

for unapproved

(See Appendix

drugs and

A.)

biologics under

-City, state, zip

FFDCA section

code of study

CRS-26

Current Law

S. 1082

H.R. 2900

S. 467

S. 484

H.R. 1561

561 [re emergency

exclusion criteria -Whether

emergency

serious diseases,

expanded protocol

situations, patient -Whether and how compassionate use situations, patient

use of the new drug, treatment uses]

access to

is available

requests for

access to

-Other data

particularly in

treatments for

single-patient and -Elements

treatments for

elements as

children

serious diseases,

expanded protocol specified by

serious diseases,

appropriate

-With sponsor

treatment uses]

use (particularly in Secretary

treatment uses]

consent, may include -Links to results

-Restrictions on

children) will be

information about the from certain FDA -Restrictions on

non-employees’

addressed

submissions, NIH non-employees’

results of included

discussion or

-Trial and

discussion or

information

trials, including

publication of

enrollment status

potential toxicities or (Medline cites and publication of

results

at individual sites

results

NLM database of

adverse effects

-Elements

product labels), and -Elements specified -Estimated

specified by

completion date

previously existing by Secretary

Secretary

-Trial location

databank entries

-RP identity and

contact

information

-Sponsor

-Funding source

-Experimental

treatments for

serious or lifethreatening

conditions

available under a

treatment

investigational

new drug

application or as a

Group C cancer

drug.

CRS-27

Current Law

Results Data

Elements

None.

S. 1082

None.

H.R. 2900

S. 467

-Registry data

elements, plus:

TECHNICAL

SUMMARY:

-Each sponsor

-Scientific point of

contact

-Description of

patient population

-Summary data

describing

achievement of

primary and

secondary

endpoints,

assessment of

secondary

endpoints, safety

information

-Information about

subjects who quit

trial

-Restrictions on

non-employees’

discussion or

publication of

results

-Link to peer

reviewed

publications

-completion date

-Title

-Unique identifier

-Product tested

-Trial description

in lay language

-Trial phase, type

-Trial purpose

-Demographic

data

-Estimated

completion date

-Study sponsor

and funding

source

-Primary,

secondary

outcome measures

-Date outcome

measures assessed

-Dates, details of

outcome revisions

-Actual

completion date,

reason for

difference from

estimate

-If terminated,

reason for

termination

-Results summary

with trial design,

S. 484

H.R. 1561

-Indication studied -Indication studied

-Safety issue

-Status of FDA

application

-Trial phase

TECHNICAL

REPORT:

-Each sponsor

-Scientific point of -Scientific point of

contact

-Description of

patient population patient population

-Summary of

aggregate data

assessing primary assessing primary

and secondary

endpoints, safety endpoints, safety

information

-Information about -Information about

subjects quit trial subjects quit trial

-Restrictions on

non-employees’

discussion or

publication of

results.

-Link to peer

reviewed

publications

-completion date -completion date

-FDA adverse

regulatory action regulatory action

CRS-28

Current Law

S. 1082

H.R. 2900

S. 467

methodology,

-FDA adverse

outcome

regulatory action

measures,

NONTECHNICAL SUMMARY: summary data

tables, statistical

-Point of contact

significance of

-General

results

description of

results, trial design -Safety data,

including adverse

changes, and

reasons for changes event information

-Peer-reviewed

BOTH

publications

REPORTS:

-Description of

-Trial purpose

results review

-Trial sponsor

process, protocol

-General

-Status of FDA

description of

results, trial design application or

reason trial not

changes, and

reasons for changes submitted to FDA

[NIH Director to

include links to

Medline citations,

NLM database

product labels,

prior databank

entries.]

Enforcement

REGISTRY:

and Corrections None specified.

General mechanisms

for enforcing

REGISTRY:

BOTH:

-RP ensures

-Sponsors of FDA

submissions not

new drug

false or misleading. false or misleading. applications

S. 484

H.R. 1561

NONTECHNICA NONTECHNICAL REPORT:

L REPORT:

-Point of contact -Point of contact

-General

description of

results, trial design results, trial design

changes, and

reasons for

changes

BOTH

REPORTS:

-Trial purpose

-Trial sponsor

-General

description of

results, trial design results, trial design

changes, and

reasons for

changes

BOTH:

-RP ensures

submissions not

false or

BOTH:

-RP ensures

submissions not

false or

CRS-29

Current Law

compliance with

FDA requirements

may be applicable,

but have not been

applied by FDA.

S. 1082

H.R. 2900

S. 467

S. 484

H.R. 1561

misleading.

-No federal agency -No federal agency submit to

-No federal

Secretary

may release

-No federal

may release

agency may

certification of

research grant

agency may

research grant

compliance with

funds to

release grant funds release research

grant funds to

noncompliant RPs. noncompliant RPs. FFDCA. If not,

to noncompliant

-Secretary consults after hearing,

noncompliant RPs.

-For applicable

RPs.

with other federal Secretary imposes -FDA

-For applicable

trials funded by

$10,000/day civil Commissioner

trials funded by

FDA, NIH, AHRQ, agencies to

determine whether monetary penalty verifies required

FDA, NIH,

or VA, progress

studies funded by until certification submissions were AHRQ, or VA,

report forms

submitted. If

them and

progress report

include

made when

conducted under 45 information is

forms include

certification of

considering

CFR 46 [re federal inaccurate and

certification of

compliance.

applications for

sponsor knew or

protections for

compliance.

Agency heads

investigational

verify compliance human subjects] are should have

drug exemptions, Agency heads

applicable clinical known, after

verify compliance

before releasing

new drug

notice and

before releasing

grant funds to RPs. trials, and to

approvals,

Secretary consults develop procedures hearing, Secretary biologics licences. grant funds to

orders sponsor to After notice to RP, RPs. Secretary

with other federal to ensure results

pay civil monetary opportunity to

submission.

consults with

agencies to

penalty of

determine whether -NIH Director

correct, Secretary other federal

$100,000 to

agencies to

studies funded by checks registry to

refuses to file

$2,000,000 for any application.

ensure

determine whether

them and

30-day period.

conducted under 45 corresponding

-Secretary checks studies funded by

-To be eligible for registry to ensure them and

CFR 46 [re federal results are filed.

After notice to RP, a federal grant,

conducted under

protections for

corresponding

contract, or

opportunity to

45 CFR 46 [re

human subjects]

results are filed.

cooperative

correct, Director

merit similar

After notice to RP, federal protections

agreement,

reports

for human

procedures.

opportunity to

noncompliance to principal

-Applications or

correct, Secretary subjects] merit

investigator

similar

submissions under federal agencies

reports

CRS-30

Current Law

S. 1082

H.R. 2900

S. 467

certifies Act

and Office of

FFDCA sections

compliance.

505, 515, 520(m), Human Research

351, or 510(k) [re Protections, posts Noncompliance,

after notice, leads

notice of

new drugs,

noncompliance in to ineligibility,

biologics and

posting of

devices], must have registry and

noncompliance

database.

certifications of

notice in database.

-FDA

compliance.

Commissioner to

-Secretary may

verify submissions -In trial with

impose FFDCA

are made for trials nonfederal

penalties for

support, Act

in applications

noncompliance.

noncompliance

under FFDCA

sections 505, 505(i) leads to notice,

515, 520(g), 351, or opportunity to

correct, hearing,

510(k) [re new or

$10,000/day

exempt drugs,

penalty until

biologics and

devices]. After 30 compliant.

days after notice,

failure to correct

leads to Secretary’s

refusal to file,

approve, or clear

application.

-Secretary to

review documents

to ensure they are

non-promotional,

not false or

misleading. 30

S. 484

H.R. 1561

noncompliance to procedures.

-NIH Director

federal agencies

checks registry to

and Office of

Human Research ensure

Protections, posts corresponding

results are filed.

notice of

noncompliance in After notice to RP,

opportunity to

registry and

correct, Director

database.

-Secretary ensures reports

content is not false noncompliance to

or misleading and federal agencies

non-promotional and Office of

Human Research

by checking a

Protections, posts

representative

notice of

sample. After

noncompliance in

notice to RP,

registry and

opportunity to

correct, Secretary database.

may impose

-Applications or

FFDCA penalties submissions under

FFDCA sections

505, 515, 351, or

510(k) [re new

drugs, biologics

and devices], must

have certifications

of compliance.

-Secretary may

impose FFDCA

penalties for

CRS-31

Current Law

Required

Studies or

Reports

None.

S. 1082

RESULTS:

The NIH Director

conducts a study to

determine the best,

validated methods

of making trial

results public after

the approval of a

drug that is the

subject of an

H.R. 2900

S. 467

S. 484

H.R. 1561

days after notice of

noncompliance,

penalties may

apply.

-Secretary may

impose FFDCA

penalties for

noncompliance,

including civil

monetary penalties

created by the Act

(not more than

$10,000/day, and

not more than

$15,000/ for all

violations of an

individual or

nonprofit

adjudicated in a

single proceeding).

noncompliance,

including civil

monetary penalties

($10,000/day for

first violation,

$20,000/day for

each subsequent

violation) created

by Act.

BOTH: Not later

than 1 year after

enactment,

Comptroller

General submits a

report to Congress

on a study to

determine whether

information in the

registry and

None required by

RESULTS:

BOTH:

Not earlier than 2 clinical trials title.

Not later than 1

years after results

year after

database

enactment,

Secretary submits established,

Comptroller

to appropriate

General initiates a

committees of

Congress a report GAO study of

on the status of the inclusion of

implementation of certain premarket

CRS-32

Current Law

Authorized

Appropriations

S. 1082

H.R. 2900

S. 467

S. 484

applicable drug

trial. Director

submits findings to

the HHS Secretary

within 18 months

of initiating the

study.

database is

considered

promotional and to

evaluate the

implementation of

the database.

Act requirements trials: burden to

including number sponsors and

and types of trials agencies, benefit

to patients and

submitted.

health providers,

REGISTRY:

recommendations.

Secretary

Makes report to

contracts with

IOM to conduct a HELP, Energy and

study of the extent 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

BOTH:

REGISTRY:

Such sums as may be $10,000,000 each

necessary; Fees

collected under

section 21 USC 379h

[re FDA prescription

drug user fees] may

not be used for the

registry.

BOTH:

$10,000,000 each

BOTH:

Such sums as may $10,000,000 each

be necessary

H.R. 1561

BOTH:

$10,000,000 each

CRS-33

Current Law

S. 1082

H.R. 2900

S. 467

Preemption

None.

BOTH:

Yes. No state or

political

subdivision of a

state may require or state may require or

effect registration effect registration

of trials or results. of trials or results.

Safe Harbor

None.

BOTH:

Somewhat.

Compliant

submissions shall

not be considered

(1) by Secretary as

evidence of a new

intended use

different from

labeling, or (2) as

FFDCA labeling,

adulteration, or

misbranding.

Effective Dates

REGISTRY:

Currently operational -Generally:

October 1, 2007

-Regulations

become effective

90 days after

issuance of HHS

Secretary’s

issuance of final

S. 484

H.R. 1561

BOTH:

Yes. No state or

political

subdivision of a

state may require

or effect

registration of

trials or results.

BOTH:

Yes. No state or

political

subdivision of a

state may require

or effect

registration of

trials or results.

BOTH:

Somewhat.

Compliant

submissions shall

not be considered

(1) by Secretary as

evidence of a new

intended use

different from

labeling, or (2) as

FFDCA labeling,

adulteration, or

misbranding.

None.

BOTH:

Somewhat.

Compliant

submissions shall submissions shall

not be considered not be considered

(1) by Secretary as (1) by Secretary as

evidence of a new evidence of a new

intended use

different from

labeling, or (2) as labeling, or (2) as

FFDCA labeling, FFDCA labeling,

adulteration, or

misbranding.

BOTH:

-Databases

established not

later than 1 year

after enactment.

Not specified.

BOTH:

Databases to be

established not

later than 1 year

after enactment.

BOTH:

-Databases

established not

later than 1 year

after enactment.

CRS-34

Current Law

S. 1082

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.

H.R. 2900

S. 467

S. 484

H.R. 1561

CRS-35

Appendix A. World Health Organization,

International Clinical Trials Registry Platform,

Registration Data Set (Version 1.0)

ITEM

DEFINITION / EXPLANATION

Primary

Trial ID #

Name of Primary Register, and the unique ID number assigned by the Primary

Date of

Registration in

Primary

Date when trial was officially registered in the Primary Register YYYY/MM/DD.

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

Monetary or

Material

Support

Major source(s) of monetary or material support for the trial (e.g., funding agency,

foundation, company).

Primary

Sponsor

The individual, organization, group or other legal person taking responsibility for

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

Sponsor(s)

Additional individuals, organizations or other legal persons, if any, that have agreed

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;

-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

Public Queries

Email address, telephone number, or postal address of the contact who will respond

to general queries, including information about current recruitment status

Contact for

Scientific

Queries

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.

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-36

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

Recruitment

The countries from which participants will be, are intended to be, or have been

recruited.

Health

Condition(s) or

Problem(s)

Studied

Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer,

medication error). If the study is conducted on healthy human volunteers belonging

to the target population of the intervention (e.g., preventative or screening

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

and Exclusion

Criteria

Inclusion and exclusion criteria for participant selection, including age and sex.

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

Enrollment

Anticipated or actual date of enrollment of the first participant (YYYY/MM).

Target Sample

Size

Number of participants that this trial plans to enroll.

Recruitment

Status

Recruitment status of this trial.

-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

Outcome(s)

Outcomes are events, variables, or experiences that are measured because it is

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

CRS-37

Secondary

Outcome(s)

Secondary outcomes are events, variables, or experiences that are of secondary

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/], visited Apr. 16, 2007.

This is a copy of a public record, reproduced as it was published. It is not legal advice, and it may not be the version a court would rely on. Check the official source before you cite it.