Clinical Trial Contracting Negotiations to Compliance NCURA WESTERN REGIONAL MEETING Presenters: Erik Lium, Ph.D. Director, Industry Contracts University of California San Francisco Lewis Barbieri Director, Office of Research and Contract Analysis University of Arizona, Tucson, AZ

Overview PRIMER FOCUS ON INDUSTRY FUNDED CLINICAL TRIALS INDUSTRY-SPONSORED INVESTIGATOR-AUTHORED NOT FOCUSING ON DEVICE TRIALS ADD’L FOCUS ON COMPLIANCE INTERACTIVE SESSION

TYPICAL CONTRACTING SITUATIONS The Basics Regulatory Bodies PARTIES AND FUNCTIONS TYPICAL CONTRACTING SITUATIONS

Regulatory Bodies Which Bodies govern Clinical Trial Research? Which rules and regulations control SAID research? How are these requirements implemented and enforced?

Clinical Trial Phases After promising treatments are explored in animal and/or laboratory studies, researchers perform clinical trials. Once the drug, device or procedure enters the clinical trials process, it must go through several phases: Phase I trials determine the safety of a new treatment Phase II trials determine efficacy and dosing for a new treatment Phase III trials study whether a new treatment is better than standard treatment Phase IV trials find more information about a new treatment that has been already approved for use in patients                                                        

Institution Review Board – “IRB” An Institutional Review Board is a group that has been formally designated to approve, monitor, and review research involving humans with an aim of protecting the rights and welfare of the subjects. FDA Regulations state the requirements for Institutional Review Boards These requirements are stated in the Code of Federal Regulations: 21 CFR Part 56, subparts A-D At any time, the FDA can audit/inspect an Institutional Review Board for compliance with said regulations and issue findings on the audit

Health Insurance Portability and Accountability Act – “HIPAA” HIPAA establishes regulations for the use and disclosure of Protected Health Information (PHI). PHI is any information about health status, provision of health care, or payment for health care that can be linked to an individual. This is interpreted rather broadly and includes any part of a patient’s medical record or payment history. Entities must disclose PHI to the individual patient within 30 days upon request. They also must disclose PHI when required to do so by law, such as reporting suspected abuse to state child welfare agencies. Entities may also disclose PHI to facilitate treatment, payment, or health care operations or if the covered entity has obtained authorization from the individual. When a covered entity discloses any PHI, it must make a reasonable effort to disclose only the minimum necessary information required to achieve its purpose.

FDA Investigator Financial Disclosure This disclosure requires that the Principal Investigator certifies that s/he does not have a significant financial holding in the company with which he wishes to contract. This helps to avoid conflict of interest situations in which the Investigator’s data may be called into question because of financial interest in the company. Financial Arrangements that require disclosure include: Compensation made to the investigator in which the value of compensation could be affected by study outcome. A proprietary interest in the tested product, including, but not limited to, a patent, trademark, copyright or licensing agreement. Any equity interest in the sponsor of a covered study, i.e., any ownership interest, stock options, or other financial interest whose value cannot be readily determined through reference to public prices. Any equity interest in a publicly held company that exceeds $50,000 in value. Significant payments of other sorts, which are payments that have a cumulative monetary value of $25,000 or more made by the sponsor of a covered study to the investigator or the investigators' institution to support activities of the investigator exclusive of the costs of conducting the clinical study or other clinical studies, (e.g., a grant to fund ongoing research, compensation in the form of equipment or retainers for ongoing consultation or honoraria) during the time the clinical investigator is carrying out the study and for 1 year following completion of the study.

Clinical Trial Contracting WHO ARE THE PARTIES TO A CLINICAL TRIAL? WHAT THE PARTIES NEED TO NEGOTIATE? WHAT IS THE APPROVAL PROCESS FOR THE FINAL DOCUMENT?

Clinical Trial Overview Sponsor Develops Protocol Provides Contractual and Budgetary guidelines to Contract Research Organization (CRO) CRO Negotiates Investigator Budget with University Negotiates Clinical Trial Terms and Conditions with University Pays University through funding supplied by Sponsor Monitors study sites for source document comparison and Case Report Form Retrieval University Sends invoices to CRO Sends final data to Sponsor or CRO Designee Indemnified by Sponsor (usually through a Letter of Indemnification)

Common “sticking points” between Sponsors/CROs and Universities in Contract Negotiation Confidentiality Protection of Sponsor Confidential Information Maintenance of Patient Records Intellectual Property Sponsor Protocol University Idea Who should own it? Publication When can results be published? Why can publication be delayed? What about multi-center publications? Indemnification Some Universities cannot reciprocate Sponsor indemnification, even for University employee’s misconduct.

Contract Process: Clinical Trial Agreements (“CTAs”) SPS/ORCA Interaction Routing the Draft Agreement Agreement comes to Investigator or Contract Office Investigator forwards agreement to Contract Office Tracking the Agreement Sponsored Programs logs agreement into University database as a draft Negotiating the Agreement Contract Office contacts Sponsor for purpose of negotiating terms of CDAs and CTAs Works as needed with: Investigator Office of Technology Transfer Office of General Counsel Risk Management Pending Finalization Sponsored Programs receives internal routing documents and fully approved budget Signing the Agreement Upon receipt of routing documents, Contracting Office executes the agreement, and forwards copies to Investigator and Study Coordinator

Typical CTA Contracting Situations WHO WRITES THE PROTOCOL? WHO PROVIDES INDEMNITY? HOW ARE THE PARTIES BOUND TO THE AGREEMENT TERMS?

Traditional Sponsored Clinical Trial Agreement Situation 1 Pharma Company University of Arizona UA and Pharmaceutical Company enter into a contractual agreement Pharma Co writes the Protocol Pharma Co offers UA full indemnification Protocol

Traditional Investigator-Initiated Clinical Trial Situation 2 Pharma Company University of Arizona UA and Pharmaceutical Company enter into a contractual agreement University PI writes the Protocol Pharma Company indemnifies UA: limited to manufacturing defects in the drug and use of the Study results Protocol

Situation 3 Incoming IIR Subcontract through Coordinating Institution Pharma Company University of Arizona Coordinating Institution UA and Coordinating Institution enter into a contractual agreement (Subcontract) Coordinating Institution has an agreement with the Pharma Company (Prime Award): Terms flow down to the Subcontract (IP, Publication, Confidentiality) Coordinating Institution PI writes the Protocol Each Institution is responsible for its own acts and omissions Pharma Co indemnifies UA for manufacturing defects in the drug and use of the Study results Indemnity Protocol

Situation 4 Incoming IIR Contract: Other Institution’s Protocol Pharma Company University of Arizona Coordinating Institution UA and Pharmaceutical Company enter into a contractual agreement Coordinating Institution has an agreement with the Pharma Company Coordinating Institution PI writes the Protocol Each Institution is responsible for its own acts and omissions as agreed in a letter of responsibility Pharma Co indemnifies UA for manufacturing defects in the drug and use of the Study results Indemnity Protocol

Outgoing IIR Subcontract through UA Situation 5 University of Arizona Pharma Company Other Institution UA and Pharmaceutical Company enter into a contractual agreement (Prime Award): Terms flow down to the Subcontract (IP, Publication, Confidentiality) UA has an agreement with the Other Institution (Subcontract) University PI writes the Protocol Each Institution is responsible for its own acts and omissions Pharma Co indemnifies UA for manufacturing defects in the drug and use of the Study results Indemnity Protocol

Compliance Overview… FEDERAL ANTI-KICKBACK STATUTE FEDERAL FALSE CLAIMS ACT REGISTRATION OF CLINICAL TRIALS

Federal Anti-Kickback Statute … Purpose: To protect patients and federal health care programs from fraud and abuse Summary: Prohibits the solicitation, receipt, offer or payment of remuneration “in return for” or “to induce” the referral of program related business, arranging for, or recommending, the purchase, lease, or ordering of any item or service reimbursed by a federal healthcare program Penalties: Civil: Fines up to $50,000 Exclusion from federal health care programs Criminal: Felony Up to five years in prison Fines up to $25,000

Anti-Kickback: Trial Risks … Direct payments to investigators Incentives for investigators (i.e. exotic meeting locations) Unbudgeted payments Financial COI Study biases (i.e. site selection, prescribing…) Excess funds Study merit

Anti-Kickback: Trial Risks & Solutions… Direct payments to investigators Institutional financial management Incentives for investigators (i.e. exotic meeting locations) Institutional contracting Unbudgeted payments Financial COI Published and enforced COI policies Study biases (i.e. site selection, prescribing, …) IRB and training Excess funds Fair market value pricing Published policies on the disposition of excess funds Study merit IRB review and approval

Federal False Claims Act … Purpose: To counteract fraudulent billing of the federal government Summary: Implicates anyone who knowingly submit claims … in order to obtain payment of a false or fraudulent claim by the federal government Intent to defraud is not required Qui Tam / Whistleblower Law Penalties: Civil: Treble damages per false claim, plus Civil penalties of $5,500 to $11,000 per false claim Criminal penalties: Predicated on willful violations

False Claims: Risks … Centers for Medicare and Medicaid Services (CMS): Medicare basics Routine clinical services vs. investigational clinical services Qualified clinical trials Double billing or billing for items covered by the Sponsor Secondary Payor (MSP)

False Claims: Medicare Basics … Centers for Medicare and Medicaid Services (CMS): Medicare general coverage: Items and services that are reasonable and necessary for the diagnosis or treatment of illness or injury Clinical Trial National Coverage Determination (NCD) Coverage: Items or services provided pursuant to trials if the items or services would otherwise be covered outside of a trial Routine clinical services of qualified clinical trials “Standard of Care” is not a defined term Exceptions apply 25

False Claims: Routine Services… Routine clinical services (covered): Items and services covered outside of a trial Items and services used for direct patient management in a trial Items or services required solely for the provision of the investigational item or service (i.e. infusion of experimental chemotherapeutic) Items or services required for the prevention, diagnosis, or treatment of complications related to an investigational item or service Investigational clinical services (not covered): Items and services being investigated as a trial objective Agency for Healthcare Research and Quality (AHRQ)

False Claims: Qualifying Clinical Trials … Qualifying Clinical Trials (QCT): Two-part test: Part 1: (all three criteria are required) Trial must investigate an item or service for which Medicare pays Trial must enroll patients with diagnosed disease Trial must have therapeutic intent Part 2: (1 out of 5 criteria required) Trial funded by AHRQ, CMS, CDC, DOD, NIH or VA Trials supported by cooperatives supported by the agencies listed in “a” Trials conducted under an IND Trials conducted under an IND exemption Trials conducted under the Coverage with Evidence Development process (rare)

False Claims: Non-QCT … Non-Qualifying Clinical Trials Nutraceuticals / Vitamins Preventative care studies Phase I drug studies Studies funded by non-qualifying government agencies Some investigator-initiated studies Routine Clinical Care under non-qualifying studies Not covered when conducted under a NQT 28

False Claims: Secondary Payor … Medicare Secondary Payor (MSP) Under MSP, a Medicare payment "may not be made . . . with respect to any item or service to the extent that payment has been made or can reasonably be expected to be made" under a primary plan. Example contract language: Unacceptable: “In the event Site is not reimbursed for routine clinical services contemplated in the Protocol, Site may remit an invoice to Sponsor.“ Acceptable: “Sponsor will be charged for items and services pursuant to the study that are not routine clinical services. Agency for Healthcare Research and Quality (AHRQ)

False Claims: Solution … Determine whether a trial is a “Qualified Clinical Trial” Convert trial protocol into a series of events Perform a coverage analysis to identify Routine clinical services Investigational clinical services Identify coverage exceptions Align the informed consent, budget, contract and planned billing practices Eliminate double billing, and billing for items covered by sponsor Eliminate contract language implicating MSP Coordinate with charge capture / billing Agency for Healthcare Research and Quality (AHRQ)

False Claims: Cases … Rush University Medical Center Settlement: Improper Medicare Billing in Clinical Trials Under September 2000 NCD On December 8, 2005, the United States Attorney’s Office for the Northern District of Illinois reached a settlement with Rush University Medical Center in Chicago, under which Rush agreed to repay approximately $1 million to the federal and state governments for inappropriate clinical trials charges submitted to Medicare and Medicaid. According … these charges relate to services and items provided … to patients enrolled in oncology clinical trials. …voluntary disclosure by Rush to federal authorities. University Of Alabama-birmingham will Pay U.S. $3.39 Million to Resolve False Billing Allegations WASHINGTON, D.C. - The University of Alabama at Birmingham and two related entities will pay the United States $3.39 million to settle allegations that they violated the False Claims Act with respect to claims submitted in connection with the school's health science research activities.

Registration of Trials: FDA … FDA Amendments Act (Public Law 110-05) Definition of clinical trial: Biologics: controlled, clinical investigations, other than Phase I investigations, of a product subject to FDA regulations Devices: controlled trials with health outcomes, other than small feasibility studies, and pediatric post-market surveillance When must registration be completed: Within 21 days of 1st subject being enrolled When must a registration be updated: Annually or within 30 days of any change in recruitment status or the completion of the study Penalties: Civil monetary penalties Loss of federal funding More information: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-014.html Guidance on New Law (Public Law 110-85) Enacted to Expand the Scope of ClinicalTrials.gov: Registration Notice Number: NOT-OD-08-014 -- (See Additional information in NOT-OD-08-023 ) Key Dates Release Date: November 16, 2007 Issued by National Institutes of Health (NIH), (http://www.nih.gov) A new law has been enacted to expand the scope of ClinicalTrials.gov. This notice provides information for NIH grantees on new responsibilities related to the first part of the law, the registration of clinical trials.  Public Law 110-85, which was enacted on September 27, 2007 [http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110.pdf] amends the Public Health Service Act to expand the scope of clinical trials that must be registered in ClinicalTrials.gov.  It also increases the number of registration fields that must be submitted, requires certain results information to be included and sets penalties for noncompliance. This notice provides information for NIH grantees and contractors on new responsibilities related to the first part of the law, the registration of clinical trials.    Additional information will be forthcoming. New Law Enacted to Expand ClinicalTrials.gov: The trials that must be registered are called “applicable clinical trials.”  Under the statute, these trials generally include:  (1) Trials of Drugs and Biologics:  Controlled, clinical investigations, other than Phase 1 investigations, of a product subject to FDA regulation; and (2) Trials of Devices:  Controlled trials with health outcomes, other than small feasibility studies, and pediatric postmarket surveillance. You should review the statutory definition of applicable clinical trial to identify if any of your trials must be registered to comply with the law [http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110.pdf ] See PL 110-85, Section 801(a), (adding new 42 U.S.C. 282(j)(1)(A)).  NIH encourages registration of ALL trials whether required under the law or not. Which Trials Must be Registered? Who is responsible? The entity responsible for registering is the “responsible party.”  The statute defines the responsible party as: (1) the sponsor of the clinical trial (as defined in 21 C.F.R. 50.3) [ http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/cfr_2003/aprqtr/pdf/21cfr50.3.pdf ], or (2) the principal investigator of such clinical trial if so designated by a sponsor, grantee, contractor, or awardee (provided that “the principal investigator is responsible for conducting the trial, has access to and control over the data from the clinical trial, has the right to publish the results of the trial, and has the ability to meet all of the requirements” for submitting information under the law.)  [http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110.pdf] See PL 110-85, Section 801(a), (adding new 42 U.S.C. 282(j)(1)(A)(ix)).  How do you determine if you are a responsible party? Investigators are encouraged to consult with their sponsored research office, institutional counsel, or other partners to determine if they are the “responsible party” for registering a trial.  It is your responsibility to determine if you are obligated to register any of your clinical trials. 1) If you are the Investigational New Drug Application (IND) or Investigational Device Exemption (IDE) holder, you may be the “sponsor” as that term is defined in the FDA regulations found at 21 C.F.R. 50.3.  For studies that are conducted under an IND or IDE, the “sponsor” is identified in the course of filing the IND (commonly called the “IND holder” or the “part 812 sponsor”) OR 2) You may not be the sponsor, but if you are the Principal Investigator you may have been delegated registration duties by the sponsor provided the other conditions for access and control over information are met.   OR 3)  For extramural trials, where there is no IND or IDE holder, NIH would not be the responsible party.  The funding recipient may be a “responsible party” as that term is defined in the Act, depending on the unique circumstances of the trial. When Must I Register My Trial? 1) Trials initiated after 9/27/2007, or trials that are ongoing as of 12/26/2007 must be registered in full by:  The later of 12/26/2007 or21 days after the first patient is enrolled. 3) Trials that were “ongoing” as of as of 9/27/2007, do involve a “serious or life threatening disease or condition,” and are completed (meaning, not “ongoing”) by 12/26/2007 are not subject to these requirements, though they may be subject to pre-existing registering requirements.   2) Trials that were “ongoing” as of as of 9/27/2007 and do not involve a “serious or life threatening disease or condition,” must be registered by 9/27/2008.   (“Ongoing” in this context means a trial had one or more patients enrolled, but had not examined the final subject or provided the final subject an intervention for the purposes of final collection of data for the primary outcome as of 9/27/2007.) What are the penalties for failing to register an “applicable clinical trial?”                                                            Penalties for responsible parties who fail to register, or provide false or misleading information in connection with, applicable clinical trials are significant  and may include civil monetary penalties and, for federally-funded trials, the withholding or recovery of grant funds.  See PL 110-85, Sections 801(a), (b), (adding new 42 U.S.C. 282(j), and new 21 U.S.C. 331(jj)). Obtaining Assistance from NIH: Existing mechanisms established by NIH ICs to assist funding recipients in registering trials with ClinicalTrials.gov can continue to be used to assist responsible parties with the new registration requirements. A list of IC liaisons is provided below.  While the NIH anticipates the continuation of this service, it is important to remember that the IC cannot in any way substitute for the responsible party in fulfilling its statutory duties. When requesting registration assistance from an IC, you are responsible for ensuring that all necessary information is provided to the IC in sufficient time to review and coordinate before the statutory deadlines described above for submission to ClinicalTrials.gov are triggered.  You will need to stay in contact with the IC liaison to ensure that your information has been registered properly.  Submission of registration information to an IC is not sufficient to satisfy the statutory obligations for submission to ClinicalTrials.gov.  Alternatively, you may register your trial directly by following the procedures outlined at http://prsinfo.clinicaltrials.gov/. Additional information on the new registration requirements is available on the PRS Web site http://prsinfo.clinicaltrials.gov/.

Registration of Trials: ICMJE … Int’l Council of Medical Journal Editors (ICMJE) Definition of clinical trail: Any … study that prospectively assigns human participants … to one or more health-related interventions to evaluate … health outcomes. Interventions include drugs, surgical procedures, devices, behavioral treatments, process-of-care changes, and the like. When must registration be completed: Prior to enrolling the 1st subject When must a registration be updated: Every 6 months Penalties: Publication of research results may be blocked by affiliate journals (NJM, JAMA, Lancet, …) More information: http://www.icmje.org/index.html#clin_trials Frequently Asked Questions Trials that began before July 1, 2005: Do trials that began before July 1, 2005 need to be enrolled before September 13, 2005 in order to be eligible for consideration at an ICMJE journal? Questions about Clinical Trials Registration Investigators should register trials that began enrolling patients any time before July 1, 2005 as soon as possible if they wish to submit them to a journal that follows the ICMJE policy. While the ICMJE hoped that all such trials would be registered by September 13, 2005, the committee understands that the policy statement was not entirely clear. Thus, ICMJE journals will consider trials that began before July 1, 2005 that were not registered prior to September 13, 2005. However, beginning on September 13, 2005, ICMJE journals will consider such trials only if they were adequately registered before journal submission. The ICMJE journals will accept "retrospective registration" of trials that began before July 1, 2005 (retrospective meaning registration occurs after patient enrollment begins). What is the ICMJE definition of an “ongoing” trial? ICMJE journals will consider trials beginning on or after July 1, 2005 only if registration occurred before the first patient was enrolled (“prospective registration”). Trials that began after July 1, 2005: The ICMJE considers trials that began enrollment before July 1, 2005 to be “ongoing” if the investigators were still collecting, cleaning, or analyzing data as of July 1, 2005. Ongoing trials require registration before submission to a journal. The most recent editorial on trails registration at www.icmje.org discusses the evolution of the ICMJE definition of clinical trials. In June 2007 the ICMJE adopted the WHO’s definition of clinical trial: “any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes.” Health-related interventions include any intervention used to modify a biomedical or health-related outcome (for example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and process-of-care changes). Health outcomes include any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events. Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) will not require registration. The ICMJE member journals will start to implement the expanded definition of clinically directive trials for all trials that begin enrollment on or after 1 July 2008. Those who are uncertain whether their trial meets the expanded ICMJE definition should err on the side of registration if they wish to seek publication in an ICMJE journal. The ICMJE secretariat office is unable to review specific studies to determine whether registration is necessary. If researchers or others have questions about the need to register a specific study, they should err on the side of registration or consult the editorial office of the journal they wish to publish the study in. What is the ICMJE definition of a clinical trial? In September 2005, the ICMJE implemented a policy that requires registration of clinically directive trials. The WHO is also working towards the implementation of an international trials registration process. Although several editors of ICMJE journals are independently involved as advisors to the WHO process, the two efforts are separate. The ICMJE welcomes the WHO initiative and is following its progress closely. When the final WHO policy is available, the ICMJE will determine whether to revise the ICMJE requirements to correspond to the WHO requirements. At present, the ICMJE expects investigators who wish to publish in ICMJE journals to adhere to the current ICMJE trials registry policy as documented on this web site (see May 2005 editorial and Frequently Asked Questions for details of the current ICMJE policy including the definition of applicable trials, acceptable registries, timing of registration, and required data items). What is the relationship between the ICMJE trials registration policy and the ongoing WHO trials registry effort? The ICMJE accepts registration in the following registries: Which trials registries are acceptable to the ICMJE? www.actr.org.au www.clinicaltrials.gov www.trialregister.nl www.umin.ac.jp/ctr/index/htm www.ISRCTN.org In addition to the above registries, starting in June 2007 the ICMJE will also accept registration in any of the primary registries that participate in the WHO International Clinical Trials Portal (see http://www.who.int/ictrp/about/details/en/index.html ). Because it is critical that trial registries are independent of for-profit interests, the ICMJE policy requires registration in a WHO primary registry rather than solely in an associate registry, since for-profit entities manage some associate registries. Trial registration with missing or uninformative fields for the minimum data elements is inadequate even if the registration is in an acceptable registry. The ICMJE is no longer the entity that reviews registries for acceptability. Registries should consult the WHO International Clinical Trials Registry Platform. Registries that the WHO designates as primary registries will be acceptable to the ICMJE. What should trial registries that wish to be ICMJE-acceptable registries do? Where can I get information about how to register a trial? Please refer to the registry that you choose to register in for instructions about the registration process for that specific registry. The ICMJE is cooperating with the WHO effort and will adopt WHO policy with respect to registry language. However, until the WHO has a mechanism in place to solve the problems of searching across registries in different languages, the ICMJE feels that the minimal data items need to be registered in English as well as in the native language of the registry. Are clinical trials registries in languages other than English acceptable to meet the ICMJE’s trials registration policy? I'm having trouble registering my trial in ClinicalTrials.gov or believe that my trial is not eligible for registration in that registry… What now? Send an email to register@clinicaltrials.gov with your question or explaining the problems you are encountering. Some trials assign health care providers, rather than patients, to intervention and comparison/control groups. If the purpose of the trial is to examine the effect of the provider intervention on the health outcomes of the providers’ patients, then investigators shoudl register the trial.If the purpose if to examine the effect only on the providers (for example, provider knowledge or attitudes), then registration is not necessary. Do I need to register a trial if the subjects were health care providers and not patients? Questions about ICMJE Membership The ICMJE (previously known as the Vancouver Group) is not an open membership organization. It is a small working group of general medical journals. Occasionally, the ICMJE will invite a new member or guest when the committee feels that the new journal or organization will provide a needed perspective that is not already available within the existing committee. Open membership organizations for editors and others in biomedical publication include the World Association of Medical Editors www.WAME.org and the Council of Science Editors www.councilofscienceeditors. However, if your journal follows the ICMJE's Uniform Requirements for Manuscripts Submitted to Biomedical Journals and you would like the ICMJE to include it on the list of journals that follow ICMJE policy on www.ICMJE.org, just send an e-mail stating that request. If you include the URL for your journal's web site, we can post a link from www.ICMJE.org to your journal. How can I join the ICMJE? Annals of Internal Medicine, British Medical Journal, Canadian Medical Association Journal, Croatian Medical Journal, JAMA, Nederlands Tijdschrift voor Geneeskunde, New England Journal of Medicine, New Zealand Medical Journal, The Lancet, The Medical Journal of Australia,Tidsskrift for Den Norske Llegeforening, and Ugeskrift for Laeger are the member journals. However, a large number of non-member journals reports that they follow the ICMJE’s Uniform Requirements for manuscripts Submitted to Biomedical Journals. Which journals are members of the ICMJE? Questions about the Uniform Requirements For Manuscripts Submitted to Biomedical Journals Can I translate/reprint the Uniform Requirements for Manuscripts Submitted to Biomedical Journals (URMs)? The ICMJE does not publish print copies of the current Uniform Requirements. The official and most current document is freely available to the public at on the ICMJE web site. Interested users can print a PDF version of this document from www.ICMJE.org. How do I obtain a print copy of the Uniform Requirements for Manuscripts Submitted to Biomedical Journals (URMs)? The ICMJE welcomes organizations to reprint/translate the URMs into languages other than English for non-profit purposes. However, the ICMJE does not have the resources to translate, to back translate, or to review or approve reprinted/translated versions of the document. Thus, any reprints/translations should prominently include the following statement: ICMJE Uniform Requirements for Manuscripts Submitted to Biomedical "This is a (insert language name) language translation/reprint of the Journals. (insert name of organization) prepared this reprint/translation with support from (insert name of funding source, if any). The ICMJE has not endorsed nor approved the contents of this reprint/translation. The official version of the Uniform Requirements for Manuscripts Submitted to Biomedical Journals is located at www.ICMJE.org. Users should cite this official version when citing the document.” How do I cite the Uniform Requirements for Manuscripts Submitted to Biomedical Journals? The ICMJE asks that anyone who reprints/translates the Uniform Requirements notify the ICMJE of that reprint/translation by sending an e-mail to the ICMJE secretariat office: claine@acponline.org International Committee of Medical Journal Editors [homepage on the Internet]. Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication [insert month/day/year you accessed site] Available from: http://www.ICMJE.org . There are only 12 journals that are official members of the ICMJE: Annals of Internal Medicine, British Medical Journal, Canadian Medical Association Journal, Croatian Medical Journal, JAMA, Nederlands Tijdschrift voor Geneeskunde, New England Journal of Medicine, New Zealand Medical Journal, The Lancet, The Medical Journal of Australia,Tidsskrift for Den Norske Llegeforening, and Ugeskrift for Laeger. Which journals follow the Uniform Requirements for Manuscripts Submitted to Biomedical Journals (URMs)? However, a large number of journals follow the URMs. A list of journals that have contacted the ICMJE to request listing as a publication that follows the URMS is available at www.ICMJE.org. There may be journals that follow the URMs that do not appear on this list. Users should also be aware that individual publications and their editors may have individual interpretations of and implementation of URM recommendations. The ICMJE cannot verify how closely listed journals follow the many specific recommendations contained within the URMs. If authors have questions about a What is the contact information or how do I submit an article to a specific journal? Questions about Other Issues particular journal to which they are considering submitting their work, they should consult the “Information for Authors” or the editorial office of that journal. Individuals with specific questions about a specific journal must contact that journal directly. The ICMJE does not maintain a directory of journals. However, some journals have included their internet addresses when requesting posting on the ICMJE’s list of journals that follow the Uniform Requirements for manuscripts Submitted to Biomedical Journals. However, if the internet address is not on the list, the ICMJE will not be able to provide you with this information. We suggest that you search for the journal of interest on the internet or consult the library at your institution. The ICMJE no longer publishes a list of reference formats, but instead recommends that authors follow the ANSI standard style adapted by the National Library of Medicine (NLM) for its databases. For samples of reference citation formats, authors should consult NLM’s Citing Medicine at www.nlm.nih.gov/citingmedicine/. How do I format a specific citation?