1. ClinicalTrials.gov and FDAAA for NIH Grantees NIH Regional Seminar – May Rebecca J. Williams, Pharm.D., MPH Assistant Director, ClinicalTrials.gov National Library of Medicine

2. Overview
Introduction to Section 801 of the Food and Drug Administration Amendments Act of 2007 (FDAAA)
Rationale
Requirements
ClinicalTrials.gov Practical Considerations
FDAAA Next steps
Protocol Registration and Results System (PRS)
Resources
NIH Office of Extramural Research (OER) Resources and Tips

3. Rationale for Trial Registration & Summary Results Reporting

4. Why Conduct Clinical Trials?
To obtain new and generalizable knowledge
Key component of the body of scientific evidence that is used to inform medical decision making

5. How It’s Supposed to Work
Clinical Trials
Journals
FDA Reviews
Systematic Reviews
Meta-analyses
Guidelines
Informed Decisions
Health Outcomes

6. Three Key Issues Not all trials are published
Publications do not always include all pre-specified outcome measures
Unacknowledged changes are made to the trial protocol that would affect the interpretation of the findings
e.g., changes to the pre-specified outcome measures

7. Zarin CTSA Webinar (10-21-09)
Kaplan-Meier estimates for ulcer complications according to traditional definition. Results are truncated after 12 months, no ulcer complications occurred after this period. Adapted from Lu Source: Jüni P, Rutjes AW, Dieppe PA. BMJ Jun 1;324(7349):
ClinicalTrials.gov / NLM 7

9. Summary of Findings
Fewer than half of NIH funded trials registered at ClinicalTrials.gov after September 2005 and completed by December 2008 were published in a peer reviewed biomedical journal indexed by Medline within 30 months of trial completion
After a median of 51 months after study completion, a third of NIH-funded trials in the sample remained unpublished
BMJ 2011;344:d7292 doi

10. Public Benefits of Access to Clinical Trial Data
Meet ethical obligation to human subjects (i.e., that results will be used to help others/inform science)
Inform future research and research funding decisions
Mitigate information bias (e.g., non publication)
Evaluate research integrity (e.g.,adherence to protocol)
Prevent duplication of trials of unsafe or ineffective interventions
Provide access to data to support evidence-based medicine
Enhance patient access to enrollment in clinical trials
All contribute to increased public trust in clinical research

11. Levels of Transparency
Zarin CTSA Webinar ( )
Levels of Transparency 11
Zarin DA, Tse T. Science
ClinicalTrials.gov / NLM

12. About ClinicalTrials.gov
Clinical studies registry and results database
Over 210,000 studies (trials & observational studies)
Studies with locations in all 50 states and 193 countries
Privately and publicly funded studies involving humans
Study information submitted by study sponsors or investigators
Web Site & registry launched in February 2000
Results database, in September 2008
Over 21,000 studies with results
Database updated daily
Usage
65,000 unique visitors per day

13. FDAAA and Other Trial Disclosure Policies

14. Why Register and Report Results?
Required by most medical journals (ICMJE*)
Registration for all clinical trials (all interventions)
It is Federal law! (FDAAA 801**)
Registration & results submission for “applicable clinical trials”
Encouraged for all NIH-supported trials
Registration & results submission, even if not subject to FDAAA 801
New NIH Policy Proposal to make this *required*
* International Committee of Medical Journal Editors
** Section 801 of the Food and Drug Administration Amendments Act of 2007

15. Other reasons …
Center for Medicare and Medicaid Services (CMS) requires NCT Number for coverage of routine costs of qualifying clinical trials
U.S. Department of Veterans Affairs (VA) requires registration and results reporting of clinical trials funded by the VA Office of Research & Development
U.S. National Cancer Institute (NCI) requires results reporting in a peer-reviewed scientific journal or ClinicalTrials.gov

16. And more reasons…
European Union requires registration and results reporting of certain drug and biologic clinical trials
Declaration of Helsinki states that all research studies involving human subjects must be registered & researchers have a responsibility to make research results publicly available
World Health Organization (WHO) considers registration a “scientific, ethical and moral responsibility” and states that there is an ethical imperative to report results
And others!!

17. “Medical advances would not be possible without participants in clinical trials,” said NIH Director Francis S. Collins, M.D., Ph.D. “We owe it to every participant and the public at large to support the maximal use of this knowledge for the greatest benefit to human health. This important commitment from researchers to research participants must always be upheld.”

18. NIH Policy Proposal Guide Notice: NOT-OD-15-019
NIH-funded awardees & investigators conducting clinical trials, funded in whole or in part by NIH
NIH-funded clinical trials must be registered and have summary results, including adverse event information, submitted to ClinicalTrials.gov
NIH revised definition of clinical trial (Oct 2014)
Includes Phase 1, all intervention types (broader than “ACT”)
Same type of registration and results data and in the same timeframes as the trials subject to FDAAA
Comment period closed March 2015
NIH Policy Proposal:
Revised NIH Definition of “Clinical Trial”:

19. NCI Clinical Trial Access Policy Guide Notice: NOT-CA-15-011
Released: January 28, 2015
Final Trial Results are expected to be reported in a publicly accessible manner (peer-reviewed scientific journal or ClinicalTrials.gov) within twelve (12) months of the Trial’s Primary Completion Date regardless of whether the clinical trial was completed as planned or terminated earlier
Will be incorporated as a Term and Condition of the award
NCI = U.S. National Institutes of Health, National Cancer Institute

20. What does FDAAA 801 require?
The responsible party for an applicable clinical trial (ACT) subject to FDAAA must :
Register the ACT in ClinicalTrials.gov no later than 21 days after enrollment of the first participant;
Update the ACT in ClinicalTrials.gov at least once every 12 months (Recruitment Status and Primary Completion Date within 30 days)
Submit summary results (including adverse event information) for certain trials not later than 1 year after the trial’s Primary Completion Date.
Delays allowed in some circumstances 20

21. The Clinical Trial Lifecycle & ClinicalTrials.gov

22. What Studies to Register?
All Clinical Trials (ICMJE)
“Applicable Clinical Trials - ACTs”* (FDAAA 801)
Interventional study of drug, biologic, or device
Exception: Phase 1 drug trials and small feasibility device trials
US FDA jurisdiction (e.g., US site or IND/IDE)
ACTs initiated on or after 9/27/07 or ongoing as of 12/26/07
*Complete definitions at:

23. Where to Register? ClinicalTrials.gov
Protocol Registration and Results System (PRS)
Log-in at:
Interactive data entry or XML upload
Tool also available for cancer centers submitting protocol information to NCI Clinical Trials Reporting Program (CTRP)
Studies conducted outside the U.S.
Be aware of all local requirements!
May also be required to register in local trial registry

24. Prior to Trial Initiation
Identify roles and responsibilities
Responsible Party* (FDAAA 801)
Sponsor
IND/IDE holder; if none, then
Person or entity who “initiated” the trial
Funding recipient if grant or sponsored research agreement
Funder if procurement funding agreement (contract)
Sponsor may designate the Principal Investigator (PI) as Responsible Party if PI meets certain requirements (e.g., has access to and control over data, right to publish)
*Complete definition at
IND/IDE= Investigational New Drug Application/Investigational Device Exemption

25. Prior to Trial Initiation (cont.)
Register the trial at ClinicalTrials.gov
Before 1st participant is enrolled (ICMJE)
Within 21 days of 1st participant enrolled (FDAAA 801)
Tip: Enter NIH Grant number in record (Secondary ID)
FDA Informed Consent Regulations (21 CFR§50.25(c))
A statement must be included in informed consent documents of applicable clinical trials initiated on or after March 7, 2012 regarding availability of information at ClinicalTrials.gov
21 CFR 50.25(c):
FDA Guidance:

26. While the Trial is Ongoing
Updates to ClinicalTrials.gov
Required at least once every 12 months (FDAAA 801)
Update/verify “active” trials once every 6 mo. (ClinicalTrials.gov)
Consider any protocol amendments that impact registration
Recruitment status and (primary) completion date must be updated within 30 days of a change (FDAAA 801)

27. Throughout Trial Lifecycle
Certification of Compliance to FDA
Form 3674 must accompany human drug, biological, and device product submissions
CMS Medicare National Coverage Determination (NCD) for Routine Costs in Clinical Trials*
Must provide NCT Number if submitting claims for routine costs that occur during a clinical trial
Mandatory as of January 1, 2015
Support Materials:

28. Throughout Trial Lifecycle (cont.)
Certification of Compliance to NIH
All grants supporting ACTs; whether grantee is RP or not
See:
Competing awards (applications):
SF 424: Part II, section 4.1.6
PHS 398: Part II, section 4.1.6
Non-competing continuation progress reports:
Research Performance Progress Report (RPPR):
All SNAP and non-SNAP awards
Section 6.7 of RPPR Instruction Guide available at:
Unrelated to the FDA certification of compliance

29. NIH Certification of Compliance: Competing applications and PHS 2590
In the “Human Subjects” section:
Add a heading entitled “ClinicalTrials.gov”
Under the heading, registered trials provide:
NCT number/s
Brief Title/s
ID and contact info for the RP
Under the heading, trials not yet registered:
Include a clear statement that the project includes an ACT which will require registration in ClinicalTrials.gov.

30. NIH Certification of Compliance: RPPR
Section G. Special Reporting Requirements
G.4.c ClinicalTrials.gov
Does this project include one or more applicable clinical trials that must be registered in ClinicalTrials.gov under FDAAA?
Yes No
If yes, provide the ClinicalTrials.gov Identifier, NCT Number (e.g., NCT ) for those trials.

31. After the Trial “Completes”
(NIH/FDA Certifications may still apply)
Definitions
Primary Completion Date - PCD (FDAAA 801)
“The date that the final subject was examined or received an intervention for the purposes of final collection of data for the primary outcome, whether the clinical trial concluded according to the prespecified protocol or was terminated.”
Study Completion Date (last subject, last visit)
Final date on which data were collected
See ClinicalTrials.gov Protocol Data Element Definitions:

32. After the Trial “Completes” (cont.)
Submit Summary Results (FDAAA 801)
Which Trials?
ACTs of FDA-approved or -cleared drugs, biologics, & devices;
Initiated on or after 9/27/07 or “ongoing” as of 12/26/07
When to Submit?
< 1 year after PCD (or < 30 days of approval or clearance)
Delays possible
Seeking approval of a new use (if Sponsor = manufacturer)
Extensions for “good cause”
Pending publication is not considered “good cause”
ACT = applicable clinical trial
PCD = primary completion date

33. After the Trial “Completes” (cont.)
Submit Summary Results
Scientific Information (“per arm”)*
Participant Flow
Baseline Characteristics
Primary and Secondary Outcome Measures
Statistical analyses, as appropriate
Adverse Events – Serious and “Other”
Administrative Information
Results Point of Contact
Certain Agreements (related to investigator’s right to publish, if not an employee of sponsor)
*ClinicalTrials.gov Results Data Element Definitions at 33 33

34. FDAAA Results Clarifications
Summary results at the end of the trial
No interim or “real-time” reporting
No participant-level reporting
Summary results submission not required for:
Registered non-ACTs (e.g., observational, Phase 1)
Trials completed by 12/26/07
Relationship to publication (ICMJE)
Submitting summary results to ClinicalTrials.gov will not interfere with publication*
(But, failing to register the trial will!) *

35. FDAAA Enforcement Provisions
Notices of non-compliance
Civil monetary penalties (up to $10,000/day)
Withholding of NIH grant funds

36. Studies Evaluating Rates of Results Reporting
Prayle et al. (2012)
Anderson et al. (2015)
Anderson et al. (2015) – subsample
Sample
Trials likely to be subject to FDAAA* completed 1/1/2009 – 12/31/2009
(analyzed Jan 2011)
Trials likely to be subject to FDAAA* completed 1/1/2008 – 8/31/2012
(analyzed Sep 2013)
Main sample + assessment of approval status of product in trial
Trials in Sample
738
13,327
205
Study Follow-up after PCD
Up to 2 years
By 12 months
Up to 5 years
Overall Rate of Results Reporting
All Trials
22%
13.4%
38.3% --
Industry
40%
17.0%
41.5%
79 – 80%
NIH 8%
8.1%
38.9%
49 – 50%
Other 7%
5.7%
27.7%
42- 45%
* Methods for determining “subject to FDAAA” were different in each analysis and both had limitations
Prayle AP et al. BMJ. 2012: Anderson M et al. N Engl J Med

37. Zarin DA et al. N Engl J Med 2015. DOI: 10.1056/NEJMc1505965
Trials by 80 Sponsors Estimated to Be Subject to Proposed Results Reporting.
Figure 1. Trials by 80 Sponsors Estimated to Be Subject to Proposed Results Reporting. Each bar represents an academic medical center or other nonprofit organization with 10 or more registered trials in the sample, arranged according to the total percentage of registered trials sponsored by that organization and estimated to be subject to at least one of the two proposed results-reporting requirements. Algorithms involving ClinicalTrials.gov data elements ( were used to estimate trials subject to each proposal. For the Food and Drug Administration Amendments Act of 2007 (FDAAA) Notice of Proposed Rulemaking (NPRM), the algorithm and data elements were an “Interventional” Study Type; a Study Phase other than “0” or “1,” at least one Intervention Type as “Drug,” “Biologic” (or “Genetic”), or “Device” (or “Radiation”); at least one Facility Country as “United States” or Investigational New Drug Application (IND) or Investigational Device Exemption (IDE) Status as “Yes” (not available publicly); and a Primary Completion Date (if missing, Study Completion Date) as “January 2008” or later. For the draft National Institutes of Health (NIH) policy, the algorithm and data elements were an “Interventional” Study Type and at least one NIH Institute or Center as Collaborator.
Zarin DA et al. N Engl J Med DOI: /NEJMc

38. The ClinicalTrials.gov Results Database

39. Results: NCT
ClinicalTrials.gov:
Publication:

40. Results: Participant Flow
Adapted from Merrill JT et al. Arthrit Rheum 2010 and NCT
Publication (CONSORT Flow Diagram)
ClinicalTrials.gov
Patients
Randomized 2:1
(n=257)
Completed Week 52
(n=64) 73%
Rituximab + Prednisone
(n=169)
Placebo + Prednisone
(n=88)
(n=120) 71%
24 Withdrawals Total
13 Adverse Events
5 Patients’ Decision
4 Physicians’ Decision
2 Lost to Follow-up
0 Death
49 Withdrawals Total
19 Adverse Events
11 Patients’ Decision
13 Physicians’ Decision
3 Lost to Follow-up
3 Death
Period 1: 52 Weeks
Placebo + Prednisone
Rituximab + Prednisone
STARTED 88
169
COMPLETED 64
120
NOT COMPLETED 24 49
Adverse Event 13 19
Patients’ Decision 5 11
Physicians’ Decision 4
Lost to Follow-up 2 3
Death

41. Results: Baseline Characteristics
Publication (“Table 1”)
ClinicalTrials.gov
Baseline Measures
Adapted from Merrill JT et al. Arthrit Rheum 2010 and NCT
Placebo + Prednisone
Rituximab + Prednisone
Total
Number of Participants 88
169
257
Age
[units: years]
Mean (Standard Deviation)
40.5 (12.8)
40.2 (11.4)
40.3 (11.9)
Gender
[units: participants]
Female 82
152
234
Male 6 17 23
Race
White 49 95
144
African American 24 40 64
Hispanic 8 32
Asian/Pacific Islander 5 11
Other 2 4
Disease duration
8.7 (7.6)
8.5 (7.2)
8.6 (7.3)

42. Results: Outcome Measures
Publication
“At week 52, no difference was noted in major clinical responses or partial clinical responses between the placebo group (15.9% had a major clinical response …) and the rituximab group (12.4% had a major clinical response …)”
Figure 2A. Proportion of patients experiencing a major clinical response (MCR) … at 52 weeks
Adapted from Merrill JT et al. Arthrit Rheum 2010 and NCT
Measured Values
ClinicalTrials.gov
Primary Outcome
Measure Title
Participants Achieving Either a Major Clinical Response (MCR) or Partial Clinical Response (PCR) Defined by British Isles Lupus Assessment Group (BILAG) Scores Over the 52-week Treatment Period
Measure Description
The BILAG Index is used for measuring clinical disease activity in Systemic Lupus …
Time Frame
Baseline to 52 weeks
Placebo + Prednisone
Rituximab + Prednisone
Number of Participants Analyzed 88
169
[units: participants]
MCR (excluding PCR) 14 21
PCR 11 29
Nonclinical Response 63
119

43. Results: Adverse Events
Publication
Serious Adverse Events
ClinicalTrials.gov
Placebo + Prednisone
Rituximab + Prednisone
Total # participants affected/at risk
32/88 (36.36%)
68/169 (40.24%)
Blood and lymphatic disorders
Neutropenia
0/88 (0.00%)
6/169 (3.55%)  
Pancytopenia
  1/88 (1.14%)  
1/169 (0.59%)  
Haemolytic Anaemia
  0/88 (0.00%)  
  1/169 (0.59%)  
Lymphophenia
Thrombocytopenia
Cardiac disorders
Coronary artery disease …. …

44. General Review Criteria
Protocol and results must be clear and informative
Review focuses on:
Logic and internal consistency
Apparent validity
Meaningful entries
Formatting 44

45. Experience with Results Database
Entering results is similar to the process of preparing a journal article
Data provider must be familiar with the study design and data analysis
Typically, the investigator and/or a statistician will need to be involved 45

46. ClinicalTrials.gov Practical Considerations

47. FDAAA - Next Steps
HHS published proposed rule for clinical trial registration and results submission under FDAAA.
Public comment period ended March 2015
Comments now under review.
Draft policy requiring all NIH clinical trial grantees to register and report results published in NOT-OD at:

48. Overview of Rulemaking Process
Food and Drug Administration Amendments Act of 2007
Announcement in Department’s Unified Agenda of Regulatory Action
Agency Develops Draft Notice of Proposed Rulemaking (NPRM)
Department and OMB Review
NPRM Published in Federal Register
Public Comment Period (typically 60 – 90 days)
Agency Responds to Comments/ Develops Final Rule
Final Rule Published in Federal Register 48

49. Determining if a Trial is an ACT
Use registration data elements to determine if study meets definition of ACT
Devices
Drugs (and Biologics)
Study Type
Interventional
Study Phase
Other than Feasibility
Controlled
Number of Arms > 2 OR
Single Arm Controlled = Yes
Intervention Type
Not Combination product
Studies FDA-Regulated Device?
Yes
FDA Jurisdiction
Facility Location in U.S. OR
Product Manufactured in U.S. OR
FDA IDE Number
- OR-
Pediatric Postmarket Surveillance of a Device?
Study Type
Interventional
Study Phase
Other than Phase 1
Controlled
Number of Arms > 2 OR
Single Arm Controlled = Yes
Studies FDA- Regulated Drug?
Yes
FDA Jurisdiction
Facility Location in U.S. OR
Product Manufactured in U.S. OR
FDA IND Number
-OR-
NPRM: Section IV.B.2 and 4; IDE = Investigational Device Exemption; IND = Investigational New Drug application

50. Results Submission Additional Issues Addressed in NPRM50
Topic Addressed
NPRM Proposal
EXTEND RESULTS SUBMISSION DEADLINE? Extend the deadline for submitting results from 12 to 18 mos.
NO. Little support from industry or patient groups
NARRATIVE SUMMARIES? Include technical and lay summaries if Secretary determines can be included without being misleading or promotional.
DEFERS DECISION. Invites additional public comment
PROTOCOLS? Require submission of the full protocol or such information as may be necessary to help to evaluate the results of the trial.
DEFERS DECISION. Invites additional public comment.
RESULTS FOR UNAPPROVED PRODUCTS? Require results for trials of drugs and devices that have not been approved by FDA? If so, deadline for submitting those results.
YES. Due within 12 months of completion date. May delay for up to 2 years w/ certification.
NPRM: Section III.C.5 to 8.

51. PRS Entry of NIH Grant Number

52. PRS Tools Protocol Registration and Results System (PRS)
NEW – Planning Report
Supports planning for when study records posted on ClinicalTrials.gov need to be updated and when results may need to be submitted
Tool to identify probable Applicable Clinical Trials
May be downloaded into a spreadsheet
Use with the Record List and Problems column on the home page to identify records that may need attention
Note: Report is for informational purposes only. The Responsible Party must determine if the trial is an “applicable clinical trial” subject to FDAAA requirements.

53. ClinicalTrials.gov PRS Resources
Protocol Registration and Results System (PRS)
General
Data element definitions
Review criteria
Recorded presentations:
Results Submission
Simple results templates
Results data preparation checklists
Example records using common study designs (e.g., parallel, cross-over, factorial, dose escalation)
Help [PRS Main Menu and data entry screens]
PRS staff:
Submit Studies > Support Materials:

54. Simple Results Templates: Basic Information Needed
* Outcome Measure Type
(Circle One) Primary Secondary Other Pre-specified Post-Hoc
Safety Issue?
(Circle One) Yes No
* Outcome Measure Title
Outcome Measure Description
* Outcome Measure Time Frame
* Arm/Group Title
Arm/Group Description
* Number of Participants Analyzed
Analysis Population Description
* Measure Type
* Measure of Dispersion/Precision
(Circle One)
Number
Mean
Median
Least Squares Mean
Geometric Mean
Log Mean
Not Applicable
Standard Deviation
Inter-Quartile Range
Full Range
Standard Error
95% Confidence Interval
90% Confidence Interval
Geometric Coefficient of Variation
[*] Category Title
* Unit of Measure
Updated with newer version of template

55. Results Data Preparation Checklists

56. Recorded Presentations
Available at:
Six presentations with audio and slides
General
Overview of ClinicalTrials.gov
Key FDAAA Issues
Results
3. Participant Flow Module
4. Baseline Characteristics Module
5. Outcome Measures and Statistical Analyses Module
6. Adverse Event Module

57. Contact Us!
If submitting results for the first time, we strongly encourage people to contact us before they begin. Our well-trained staff can provide 1-on-1 assistance with any results submission. us at:

58. NIH OER Resources and Tips

59. NIH OER Resources “What NIH Grantees Need to Know about FDAAA”
Step-by-step guidance
Flowcharts for ascertaining ACTs and RP
“At-a-glance” requirements
FAQs for NIH Grantees

60. Tips: Take a Team Approach
Be aware of your Institution’s approach/SOP
Work as a team to identify ACTs and RPs
Sponsored research office, PI, Counsel
Work across institutions
Take actions early to clarify roles and responsibilities
NIH’s role
Resources
Cannot make determinations or register/report results on behalf of Grantee or RP

61. Tips: Plan Ahead
Are the costs (including staff time) of … reporting … in ClinicalTrials.gov allowable charges on an NIH grant?
Given the nature of this requirement and that the project staff will generally be in the best position to submit and maintain these data, the costs of FDAAA compliance will generally be allowable as direct charges to NIH supported grants. While it is expected that these costs will be covered by the funds provided with the grant, administrative supplements could also be considered.
NIH Grants FAQs:

62. Tips: Manage Risk Wisely
Grantee Institutions as Sponsors
Do you have standard operating procedures?
Including process for when key staff leave the institution
Training
Monitor compliance
How will you ensure trials are registered and results reported?
(Some institutions require NCT Number for IRB approval)
Use personnel appropriately to fulfill FDAAA
Not necessary to have PI designated as RP in order for him/her to enter data
Plan for registration and results reporting early in the trial development process
Implement appropriate record retention

63. Tips: Understand FDAAA
Responsible Party must register and submit results for applicable clinical trials (ACTs)
Informed Consent
Updates throughout trial lifecycle
Certifications of Compliance
Be attentive to rulemaking and potential NIH policy
Last estimated date for publication was May 2016, but not yet sent to OMB for review
Draft policy requiring all NIH clinical trial grantees to register and report results published in NOT-OD

64. Tips: Create culture of disclosure
The NIH encourages registration and results reporting for all NIH-supported clinical trials, regardless of whether or not they are subject to FDAAA
FDA Compliance Program : Sponsors, Contract Research Organizations, and Monitors*
Instructs FDA staff to identify SOPs and determine if studies were registered on ClinicalTrials.gov appropriately *

65. NIH Grants Contact Information
Division of Grants Policy:
Phone:
Division of Grants Compliance & Oversight:

66. Select Publications
Available at:
Zarin DA, Tse T, Ross JS. Trial-results reporting and academic medical centers. N Engl J Med May 20.
Zarin DA, Tse T, Williams RJ, Califf RM, Ide NC. The ClinicalTrials.gov results database – update and key issues. N Engl J Med 2011;
Tse T, Williams RJ, Zarin DA. Reporting basic results in ClinicalTrials.gov. Chest 2009;136:

67. Additional Resources Contact us: register@clinicaltrials
Additional Resources Contact us: ClinicalTrials.gov information (Submit Studies page): Office of Extramural Research (OER) Food and Drug Administration (FDA) ls/FDAsRoleClinicalTrials.govInformation/default.htm