NIH Releases Proposed Rule on FDAAA Requirements for ClinicalTrials.Gov Registration and Results Submission

NIH has just released a proposed rule that would clarify and expand requirements for the submission of clinical trial registration and results information, including adverse event information, to the ClinicalTrials.gov database in conformance with the Food and Drug Administration Amendments Act of 2007 (FDAAA). The rule would implement the statutory requirement for the submission of summary results information for trials involving drugs, biological products, and devices that are approved, licensed, or cleared by FDA, and it proposes to extend such requirements to clinical trials of drugs, biological products, and devices that are not approved, licensed, or cleared by FDA. Among other things, the proposed rule would require the responsible party (i.e., the trial sponsor or principal investigator) to register an applicable clinical trial no later than 21 days after enrolling the first participant, and results generally would be required to be submitted no later than 1 year after the completion date of the clinical trial (the date of final data collection for the primary outcome measure studied). Results submission could be delayed for up to two additional years with certification that either an unapproved, unlicensed, or uncleared product studied in the trial is still under development by the manufacturer or that approval will be sought for a new use of an approved, licensed, or cleared product that is being studied in the trial. Extension requests also could be submitted for “good cause.” With regard to adverse events reporting, the proposed rule would require the responsible party to submit information summarizing the number and frequency of adverse events experienced by participants enrolled in a clinical trial, by arm and organ system, and it specifies the form of that reporting. The proposed rule would require submitted information to be updated at least annually if there are changes to report, with provisions for more rapid updating in certain circumstances. The proposed rule does not impose requirements on the design or conduct of clinical trials or on the data that must be collected during clinical trials. The proposed rule is scheduled to be published on November 21, 2014, and comments will be accepted for 90 days after publication.

Draft HHS Guidance on Disclosing Risks in Standards of Care Research

On October 24, 2014, the HHS Office for Human Research Protections published a notice announcing that it is seeking comments on draft guidance for the research community entitled “Guidance on Disclosing Reasonably Foreseeable Risks in Research Evaluating Standards of Care.” The guidance addresses risks to subjects that are presented by research evaluating risks associated with standards of care, and which of these risks are reasonably foreseeable and should be disclosed to prospective research subjects as part of their informed consent. Comments on the guidance will be accepted until December 23, 2014. 

FDA Seeks Comments to Updated Guidance on Informed Consent in Clinical Trials

This post was written by Jennifer Pike and Vicki Morris.

Earlier this summer, the Food and Drug Administration (FDA) issued a draft 42-page "Informed Consent Information Sheet" that provides guidance for institutional review boards (IRBs), clinical investigators, and clinical trial sponsors on complying with the Agency’s informed consent regulations. Once finalized, the draft guidance will supersede FDA’s previous Information Sheet on this topic, "A Guide to Informed Consent," which was last updated over 15 years ago, in 1998.  The guidance, which is a compilation of FDA’s regulations and past guidances on informed consent, also reflects the Agency’s coordinated efforts with the Department of Health and Human Services (HHS) to facilitate consistency across informed consent requirements and policies among federal government agencies.

Broadly, the new guidance indicates FDA policy shifting towards enhanced informed consent processes. More narrowly, the draft guidance explains the various and often caveated elements of informed consent (including providing patients with a description of the trial, its risks, benefits, alternative treatments, confidentiality and compensation in the event of injury), depicts the detailed responsibilities of IRBs, clinical investigators and sponsors of clinical trials (including compliance with the process, elements and documentation of informed consent), and provides examples of recommended language to assist industry parties in complying with FDA’s informed consent regulations. FDA accomplishes this task by clarifying some aspects of existing guidance and creating additional guidance in new areas.

The following provides an overview of some of the draft guidance’s notable new and revised provisions.

  • Risks and discomforts: In a new policy, FDA states that “all possible risks do not need to be described in detail in the informed consent form, especially if it could be overwhelming for subjects to read.” Instead, FDA states that only risks that are more likely to occur and those that are serious should be included. This is a change from the 1998 information sheet in which FDA stated that “[a]ny procedures relating solely to research…should be explained to the subjects.”
  • Alternative procedures: Like FDA’s new stance on risks and discomforts, the Agency does not require that all alternative treatments be explained. Unlike the 1998 information sheet, which stated that “subjects should be aware of the full range of options available to them,” now the Agency states that “it may be appropriate to refer the subject to a healthcare professional who can more fully discuss the alternatives.” Although FDA clarifies that such a referral should be completed before the subject signs and dates the informed consent form, the question remains as to how an investigator should document the referral.
  • Off-label use disclosure: FDA clarifies in the guidance that disclosures of alternative treatment, as required under 21 C.F.R. 50.25(a)(4), must include a description of medically recognized standards of care, which may include off-label uses of approved products. FDA’ position on the disclosure of off-label uses is likely to create a new burden for investigators and sponsors to determine when an off-label use of a product has become a “standard of care.”
  • Impaired consent capacity: The guidance introduces a new section on obtaining informed consent of patients with impaired consent capacity, ranging from minor or temporary impairments to complete or permanent impairments. In these cases, FDA suggests that clinical trial enrollment forms may require modification, and that investigators should consider if including patients with impaired consent capacity is “ethically appropriate and scientifically necessary.”
  • Alternative methods of obtaining informed consent: In this new section, FDA recognizes that new technologies (e.g., fax or email) may be used as part of the consent process and may serve as an alternative to the traditional paper consent form. FDA encourages those interested in pursuing alternative methods of obtaining informed consent to contact the Agency and provide comments on these alternative methods.
  • Reviewing patient records: The guidance indicates that sponsors and investigators may seek to review patient medical records for a variety of reasons related to a clinical investigation, such as to determine if a patient is eligible for a clinical trial or to retrospectively review the records of a previously enrolled patient. Whether consent or “reconsent” of the patient is necessary is determined on a case-by-case basis. Apart from a potential need for consent, sponsors and investigators must also consider the need to comply with federal and state privacy laws, such as HIPAA.
  • Multiple trial participants: FDA “strongly discourages” the practice of individual patients participating in multiple and simultaneous clinical trials or enrolling in a single clinical investigation multiple times. The Agency’s rationale is partly due to medical safety reasons for the patient, and also due to the high likelihood of trial subjects not fully understanding all the risks, proposed benefits and demands of multiple trial protocols, thereby delegitimizing informed consent.
  • Affirmative right to compensation for injury: Expanding FDA regulation that requires informed consent documents to include a “statement that compensation or medical treatment are or are not available if unanticipated injuries occur and of what they consist,” the draft guidance encourages sponsors to include in informed consent forms an affirmative statement that subjects are “not precluded from seeking to collect compensation for injury related to malpractice, fault or blame on the part of those involved in the research.”

In addition to the above new and expanded sections, the guidance also offers additional insight into topics such as “assent” to research by children, informed consent of non-English-speaking clinical trial participates, and when to disclose to subjects when an investigator conflict of interest exists or when a study has been suspended or terminated.

The new guidance raises many questions and considerations for clinical trial sponsors, investigators and IRBs and provides an important opportunity for these industry parties to provide comments to FDA. Comments on the draft guidance are due to FDA by September 15, 2014 and can be submitted here.

About the Authors: Jennifer Pike (associate) and Vicki Morris (Law Clerk) are members of the firm’s Life Sciences Health Industry Group and is based in our Washington, D.C. office.

Ways and Means Committee Seeks Comments on Medicare Program Integrity Bill

The Chairman of the House Ways and Means Subcommittee on Health is seeking comments on a draft bill, the Protecting Integrity in Medicare Act of 2014, that is “aimed at combating fraud, waste and abuse in the Medicare program.” The bill covers a range of Medicare and Medicaid policies, from establishing new alternative sanctions for technical physician self-referral violations to providing more flexibility in meeting durable medical equipment (DME) documentation requirements. Among other things, the bill would: 

  • Establish an alternative fixed financial penalty for individuals and entities that voluntarily disclose a technical Stark violation (e.g., an arrangement that is not in writing or that is not signed by one or more parties) through the Self-Referral Disclosure Protocol; the per-arrangement penalty would be capped at $5,000 if submitted within the year of the noncompliance and $10,000 thereafter;
  • Require a study on how to establish a permanent physician-hospital gainsharing program;
  • Expand the professionals who can document DME face-to-face encounters beyond physicians to align with the professionals who can furnish such encounters;
  • Establish claims processing edits to prevent Medicare payments for incarcerated, unlawfully present, and deceased individuals;
  • Require Medicare administrative contractors (MACs) to establish improper payment outreach and education programs, and modify how MACs prioritize efforts to reduce improper payment or error rates;
  • Allow Medicaid fraud control units to investigate abuse and neglect in home and community based facilities;
  • Provide the HHS OIG with up to 1.5% of all amounts collected from Medicare false claim and fraud cases;
  • Give the Secretary greater flexibility to protect Medicaid from fraud, waste, and abuse;
  • Improve incentives for individuals to report Medicare fraud and abuse under the Senior Medicare Patrol;
  • Require valid prescriber National Provider Identifiers to be included on pharmacy claims;
  • Revise the process for renewing MAC contracts;
  • Create a high-risk beneficiary drug management program under the supervision of a Part D plan sponsor;
  • Require the Secretary to issue guidance on the application of the “Common Rule” to clinical data registries;
  • Revoke eligibility for Medicare benefits for providers convicted of defrauding the Medicare program under certain circumstances;
  • Require home health agencies to obtain a surety bond in the amount of at least $50,000 as a condition of Medicare participation;
  • Require prior authorization (PA) for certain chiropractic visits, blepharoplasty, and browplasty surgeries and expand a PA demonstration for non-emergent ambulance services;
  • Require Social Security numbers to be removed from beneficiary Medicare cards; and
  • Require the Secretary to include vacuum erection systems in the DME competitive bidding program by 2016.

Subcommittee Chairman Kevin Brady (R-TX) will accept comments on the discussion draft until September 1, 2014.

July Congressional Health Policy Hearings

Congressional panels have held numerous hearings on health policy issues this month, including the following:

  • The House Energy and Commerce Committee held a series of hearings on its “21st Century Cures” initiative, focusing on personalized medicine, barriers to evidence development and communication, technological innovations, the patient perspective, and modernizing clinical trials. A separate hearing focused on ACA’s insurance eligibility verification system. Coming up, the Committee will examine plan “bailouts” and cancellations under the ACA (July 28) and the status of ACA payment and verification systems (July 31).
  • The Ways and Means Committee held hearings on the integrity of the ACA’s premium tax credit verification system and the future of Medicare Advantage health plans.
  • The House Oversight Committee held a hearing on Medicare appeals reform.
  • The House Science, Space, and Technology Committee examined “Policies to Spur Innovative Medical Breakthroughs from Laboratories to Patients.” 
  • A Senate Finance Committee hearing focused on chronic illness and patients’ unmet needs.
  • The Senate Health, Education, Labor and Pensions Committee examined preventable deaths and improving patient safety. The Committee also approved a number of bipartisan bills, including S. 315, the "Paul D. Wellstone Muscular Dystrophy Community Assistance, Research and Education Amendments; S 2154, the Emergency Medical Services for Children Reauthorization Act; S. 2405, the Trauma Systems and Regionalization of Emergency Care Reauthorization Act; S. 2406, the Improving Trauma Care Act; and S. 2539, the Traumatic Brain Injury Reauthorization Act.

FDA Meeting on Biomarker Development (Sept. 5)

On September 5, 2014, the FDA is holding a public meeting at the Washington Plaza Hotel, in Washington DC, to discuss current scientific and regulatory approaches to biomarker development, acceptance, and utility in the development of therapeutic products (e.g., drugs and biologics). Specifically, FDA will focus on (1) identifying challenges for biomarker applications in early- and late- phase clinical trials, and (2) emerging best practices for successful biomarker-based programs (including codevelopment of in vitro diagnostic devices and use of biomarkers as outcome measures in clinical trials). Public input from the meeting will be used to identify opportunities for biomarker-related regulatory guidance, improve understanding and consistency in regulatory review of therapeutic product applications that incorporate biomarkers in clinical trial designs, and identify potential strategies to facilitate scientific exchanges in regulatory and non-regulatory contexts. For more information on the meeting, which is being held in collaboration with Brookings Institution, and for early registration deadlines to attend the live meeting, see the FDA announcement.  FDA will also accept comments on this topic through November 5, 2014.

Full Energy and Commerce Committee Approves Three Bipartisan Health Bills

On June 10, 2014, the full House Energy and Commerce Committee approved by voice vote three bipartisan public health bills:

  • H.R. 4299, “Improving Regulatory Transparency for New Medical Therapies Act,” which is intended to improve the Drug Enforcement Agency scheduling process for new FDA-approved drugs under the Controlled Substances Act and the registration process for the use of controlled substances in clinical trials to allow treatments to get to patients in a more timely and predictable manner.
  • H.R. 4709, “Ensuring Patient Access and Effective Drug Enforcement Act,” which would amend the Controlled Substances Act to clarify definitions, allow parties to submit a corrective action plan prior to revocation or suspension of a registration, and require a report identifying how collaboration between agencies and stakeholders can benefit patient access to medications and prevent diversion and abuse of controlled substances.
  • H.R. 4631, the "Autism Collaboration, Accountability, Research, Education and Support (CARES) Act," which would continue autism-related federal research, early identification and intervention, education, and activities of the Interagency Autism Coordinating Committee.

House Energy and Commerce Subcommittee Approves Health Bills

On May 28, 2014 the House Energy and Commerce Subcommittee on Health approved by voice vote three bipartisan public health bills:

  • H.R. 4299, “Improving Regulatory Transparency for New Medical Therapies Act,” which is intended to improve the Drug Enforcement Agency scheduling process for new FDA-approved drugs under the Controlled Substances Act and the registration process for the use of controlled substances in clinical trials to allow treatments to get to patients in a more timely and predictable manner.
  • H.R. 4709, “Ensuring Patient Access and Effective Drug Enforcement Act,” which would amend the Controlled Substances Act to clarify definitions, allow parties to submit a corrective action plan prior to revocation or suspension of a registration, and require a report identifying how collaboration between agencies and stakeholders can benefit patient access to medications and prevent diversion and abuse of controlled substances.
  • H.R. 4631, “Combating Autism Reauthorization Act of 2014,” which would continue autism-related federal research, early identification and intervention, education, and activities of the Interagency Autism Coordinating Committee.

FDA Releases Final Guidance on Qualification Process for Drug Development Tools

This post was written by Jennifer Pike.

The Food and Drug Administration (FDA) has announced the availability of a final guidance document which describes the qualification process for drug development tools (DDTs) intended for use, over time, in multiple drug development programs. DDTs are methods, materials, or measures that aid drug development. Examples of DDTs include biomarkers and patient reported outcome instruments.

The purpose of the guidance document is to describe the formal process that FDA will use in working with sponsors of DDTs to guide them as they refine the tools and rigorously evaluate them for use in the regulatory process. The guidance also provides a framework for interactions between FDA and sponsors to support work towards qualification of DDTs, as well as explains the kinds of data that should be submitted to support qualification of a DDT and creates a mechanism for FDA’s formal review of the data to ultimately qualify the DDT. For purposes of the guidance, the submitter of a DDT is the person, group, organization (including the federal government), or consortium that takes responsibility for and initiates a DDT qualification proposal using the procedures described in the guidance.

The creation of the DDT qualification process is one of multiple initiatives FDA has undertaken, as a result of its 2004 FDA’s Critical Path Initiative, to support the development of new DDTs. DDTs can help streamline the drug development process, improve the chances for clinical trial success, and yield more information about a treatment or disease. Comments to the guidance may be submitted at any time at www.regulations.gov.

CMS Updates Medicare Physician Fee Schedule, Other Part B Policies for CY 2014

On December 10, 2013, CMS published its final rule updating Medicare physician fee schedule (PFS) rates and polices for calendar year (CY) 2014, which includes a 20.1% across-the-board cut in PFS rates in 2014 (down from 24.4% projected under the proposed rule). The cuts are largely due to the statutory Sustainable Growth Rate (SGR) update formula, although lawmakers are seeking agreement on legislation to block the automatic cuts. The rule also includes a number of significant Part B policy changes, including the following highlights:
 

  • The final 2014 conversion factor (CF) is $27.2006, compared to the 2013 CF of $34.0230, mainly as a result of the statutory SGR formula. Congress is expected to override this formula, either on a temporary or permanent basis, but final action is still uncertain (see legislative update below). CMS estimates that if Congress freezes the PFS update for 2014, it would actually result in a CF of $35.6446, an increase compared to 2013, due to the application of a budget neutrality adjustment. Reimbursement changes for individual procedures vary based on numerous other policies. 
  • CMS did not finalize a controversial proposal under its potentially misvalued code initiative to reduce PFS rates for more than 200 codes if Medicare physician office payment exceeds the payment under the hospital outpatient prospective payment system (OPPS) or ambulatory surgical center (ASC) prospective payment system (PPS). CMS expects to develop a revised proposal for using OPPS and ASC rates in establishing physician practice expense relative value units, which CMS will propose through future notice and comment rulemaking. CMS is continuing its efforts to identify and adjust payment for potentially misvalued codes, however, including by adopting on an interim basis work relative value units for approximately 200 additional codes. These interim values are subject for public comment until January 27, 2014.
  • CMS will make payment for non-face-to-face complex chronic care management services for Medicare beneficiaries who have multiple (two or more) significant chronic conditions, beginning in 2015. CMS will establish practice standards for such chronic care management services through future rulemaking. 
  • CMS is modifying the definition of eligible telehealth originating sites to include health professional shortage areas (HPSAs) located in rural census tracts of urban areas as determined by the Office of Rural Health Policy, which CMS expects to result in the inclusion of additional HPSAs as areas for telehealth originating sites. CMS is adding transitional care management services to the list of eligible Medicare telehealth services.
  • CMS will continue implementation of the physician value-based payment modifier, which was mandated by the Affordable Care Act (ACA) to reward physicians for providing higher quality and more efficient care. The value modifier is being phased in from CY 2015 to CY 2017. CY 2014 is the performance period for the CY 2016 value modifier. CMS is finalizing plans to apply the value modifier to groups of 10 or more eligible physicians in 2016 (compared to groups of 100 or more in 2015), and increase the amount of payment at risk from 1% to 2% in 2016. CMS also is refining the methodologies used to calculate the value modifier to better identify both high and low performers for upward and downward payment adjustments. 
  • CMS has adopted its proposal to amend the “incident to” regulations to require that services and supplies be furnished in accordance with applicable state law, and that the individual performing “incident to” services meet any applicable requirements to provide the services, including state licensure requirements. The policy is intended to ensure that auxiliary personnel providing services to Medicare beneficiaries “incident to” the services of other practitioners do so in accordance with applicable state requirements, and that Medicare payments can be recovered when such services are not furnished in compliance with the state law.
  • CMS has adopted without change its proposed process to systematically reexamine payment amounts under the Clinical Laboratory Fee Schedule to determine if changes in technology for the delivery of that service (e.g., changes to the tools, machines, supplies, labor, instruments, skills, techniques, and devices by which laboratory tests are produced and used) warrant an adjustment to the payment amount. Beginning with the CY 2015 PFS proposed rule, CMS will identify the test code, discuss how it has been impacted by technological changes, and propose an associated payment adjustment. CMS will solicit comments, and any payment adjustment would be adopted in the final rule, beginning with the CY 2015 final rule. 
  • CMS is establishing a centralized review process under which a single entity will make Investigational Device Exemption (IDE) coverage decisions, although the policy will not be implemented until 2015. The rule also establishes minimum standards for IDE studies and trials for which Medicare coverage of devices or routine items and services is provided (but CMS dropped earlier references to pivotal study and superiority study design criteria). 
  • CMS will apply the outpatient therapy cap limitations and related policies to outpatient therapy services furnished in a critical access hospital beginning on January 1, 2014, in conformance with the American Taxpayers Relief Act (ATRA). 
  • The final rule also addresses, among many other things: updates to the geographic practice cost indices; revisions to the calculation of the Medicare Economic Index; revisions to the Physician Quality Reporting System and the Electronic Health Record (EHR) Incentive program; revisions to regulations regarding liability for overpayments to conform to ATRA provisions with regard to the timing of the triggering event for the ‘‘without fault’’ and ‘‘against equity and good conscience’’ presumptions; and updates to the ambulance fee schedule regulations to conform with statutory requirements. 

In light of the late release of the final Medicare PFS rule, CMS is extending the annual Medicare participation enrollment period for 2014 through January 31, 2014 (instead of the window ending on December 31, 2013). During this period, eligible physicians, practitioners, and suppliers may change their participation status, but the effective date for any participation status changes remains January 1, 2014.

OIG Examines Clinical Trial Data and Safety Monitoring Boards

The OIG has issued a report entitled “Data and Safety Monitoring Boards in NIH Clinical Trials: Meeting Guidance, But Facing Some Issues.” The report examines the effectiveness of data and safety monitoring boards (DSMB) – or committees of experts that provide ongoing reviews of clinical trial data to ensure the safety of study subjects and validity and integrity of data. Based on a review of 44 National Institutes of Health (NIH) funded Phase III multi-site clinical trials that were completed in 2009 and 2010 that entailed potential risk, the OIG concluded that DSMBs met general NIH guidance in this area, including with regard to the experience of DSMB members. The OIG identified several potential issues, however, including that NIH participation in closed DSMB meetings diminishes the appearance of independence and not all NIH Institutes and Centers (IC) policies reference DSMB access to unmasked data. Based on these findings, the OIG recommends that NIH: direct ICs to delineate the circumstances in which IC staff should participate in DSMB meetings; direct IC DSMB policies to explicitly reference DSMB access to unmasked data, and identify ways to recruit and train new DSMB members. NIH concurred with the recommendations. 
 

HHS Seeks Comments on IRB Assessment of Risks in Standard of Care Interventions Research; Aug. 28 Meeting Scheduled

The Department of Health and Human Services (HHS) is seeking input on how institutional review boards (IRBs) should assess the risks of research involving randomization to one or more treatments within the standard of care for particular interventions, and what reasonably foreseeable risks of the research should be disclosed to research subjects as part of the informed consent process. In a June 26, 2013 notice, HHS states that it “has become aware of differing perspectives in the scientific, research, and ethics communities about these issues and how the relevant requirements of the HHS protection of human subjects regulations should apply to research studying standard of care interventions.” To inform future guidance, HHS is hosting a meeting on this topic on August 28, 2013, and the agency is seeking public comment on a variety of related questions; comments will be accepted through September 9, 2013. 

Bioethics Panel Seeks Comments on Ethical/Legal Issues Involving "Incidental Findings" in Research and Testing

The Presidential Commission for the Study of Bioethical Issues is requesting public comment on the ethical, legal, and social issues raised by “incidental findings” (e.g., information obtained from testing that was not its intended or expected object) that arise from genetic and genomic testing, imaging, and testing of biological specimens conducted in the clinical, research, and direct-to-consumer contexts. The Commission is particularly interested in receiving public commentary regarding:

  • The likelihood of such incidental findings and any related case studies;
  • What, if anything, patients, participants, and/or consumers should be told about incidental findings resulting from large-scale genetic testing, imaging, and testing of biological specimens before tests are conducted;
  • Any duties or ethical obligations that clinicians, researchers, and direct-to-consumer companies might have to actively look for certain incidental findings;
  • Best practices, methods, and mechanisms for determining when and how incidental findings should be returned to patients, participants, and/or consumers;
  • The acceptability of holding back information--such as establishing “no return” policies, or advance stipulations that no incidental findings will be returned; and,
  • Any best practices or recommendations regarding incidental findings that apply no matter the type of test or context.

Comments will be accepted until July 5, 2013. Additional information about the Commission’s work in this area is available here.  

FDA Issues New Draft Guidance Documents on Access to Investigational Drugs

This post was written by Jennifer Pike.

On May 9, 2013, the Food and Drug Administration (“FDA”) announced the availability of two new draft guidance documents answering common questions on FDA’s implementation of regulations related to access to investigational drugs. The first draft guidance, entitled “Charging for Investigational Drugs Under an IND – Qs & As,” addresses FDA’s implementation of 21 C.F.R. § 312.8 and answers the most frequently-asked questions about charging for investigational new drugs under an investigational new drug (IND) Application (IND). The regulation, which went into effect in October 2009, clarifies the circumstances under which charging for an investigational new drug in a clinical trial is appropriate. It also sets forth criteria for charging for an investigations drug and clarifies what costs can be recovered for an investigational drug.

The second draft guidance, entitled “Expanded Access to Investigational Drugs for Treatment Use – Qs & As,” answers the most frequently-asked questions related to FDA’s implementation of its expanded access regulations (21 CFR Part 312, Subpart I). The regulations, which went into effect on October 2009, contain the requirements for the use of investigational new drugs or approved drugs where availability is limited by a risk evaluation and mitigation strategy, when the primary purpose is to diagnose, monitor, or treat a patient’s disease or condition.

Comments on the draft guidance documents should be submitted in writing, or electronically at www.regulations.gov, on or before July 8, 2013.

FDA Issues New Guidance Documents

This post was written by Jennifer Pike.

In recent weeks, the Food and Drug Administration (FDA) has issued a number of new draft and final guidance documents on a range of issues, including financial disclosure by clinical investigators, medical device recalls, prescription drug labeling, and medical devices for pediatric uses. Highlights include the following:

FDA Releases Draft Guidance Documents on Providing Submissions in Electronic Format

This post was written by Jennifer Pike.

The FDA released draft guidance on January 3, 2013 entitled Providing Regulatory Submissions in Electronic Format – Certain Human Pharmaceutical Product Applications and Related Submissions Using eCTD Specifications. The guidance is being issued in accordance with the Food and Drug Administration Safety and Innovation Act, which amended to Federal Food, Drug, and Cosmetic Act to require that certain regulatory submissions be submitted in electronic format. The guidance describes how FDA plans to implement this requirement. According to the guidance, requirements for electronic submission will be phased in on the following schedule: (1) 24 months after publication of the final version of this draft guidance, the requirements will apply to new drug application (NDA), abbreviated new drug application (ANDA), and biologics license application (BLA) submissions, and (2) 36 months after publication of the final guidance, the requirements will apply to investigational new drug application (IND) submissions. Comments will be accepted until March 4, 2013. A second draft guidance document, Providing Submissions in Electronic Format – Summary Level Clinical Site Data for CDER’s Inspection Planning, is intended to assist applicants in the voluntary submission of a clinical dataset that describes and summarizes the characteristics and outcomes of clinical investigations at the individual study site level. Such datasets facilitate the use of a risk-based approach to timely identification of clinical investigator sites for onsite inspection by FDA during the review of marketing applications. The guidance describes a recommended electronic format for the datasets to be submitted voluntarily in NDA, BLA, and NDA and BLA supplemental applications submitted to CDER. Comments may be submitted to www.regulations.gov by February 19, 2013.

FDA Draft Guidance Addresses Clinical Trial Enrichment

This post was written by Jennifer Pike.

The FDA is seeking comments on draft guidance related to clinical trial enrichment: Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products. The document is designed to provide guidance to industry on enrichment strategies that can be used in clinical trials intended so support effectiveness and safety claims in NDAs and BLAs. According to FDA, enrichment could lead to smaller studies, lower development costs, and help develop more personalized medicine. The guidance defines and discusses three types of enrichment strategies: decreasing heterogeneity, predictive enrichment, and prognostic enrichment. The guidance also discusses general clinical trial design considerations, provides examples of various potential clinical trial designs, and discusses potential regulatory considerations when using enrichment strategies in clinical trials. Comments may be submitted at www.regulations.gov until February 15, 2013.

FDA Issues Two Final Guidances on Safety Reporting Requirements

This post was written by Jennifer Pike.

The FDA has released two final guidance documents intended to help sponsors and investigators comply with safety reporting requirements for IND applications and bioavailability (BA) and bioequivalence (BE) studies: Safety Reporting Requirements for INDs and BA/BE Studies, and Safety Reporting Requirements for INDs and BA/BE Studies – Small Entity Compliance Guide. Comments regarding both guidance documents may be submitted at any time.

FDA Issues Two New Draft Guidance Documents Related to the Conduct of Clinical Trials

This post was written by Jennifer Pike.

The Food and Drug Administration (FDA) recently issued two draft guidance documents related to the conduct of clinical trials. The first draft guidance, Draft Guidance for IRBs, Clinical Investigators and Sponsors: IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE Is Needed is intended to assist institutional review boards (IRBs), clinical investigators, and sponsors involved in clinical investigations of FDA-regulated products in determining whether the proposed research satisfies the criteria for IRB approval. Specifically, the guidance addresses the IRB’s role in reviewing: (1) the qualifications of investigators; (2) the adequacy of research sites; and (3) the determination of whether an investigational new drug (IND) application or investigational device exemption (IDE) is needed. Many of the recommendations in the guidance have appeared in other FDA guidance documents or have been communicated to IRBs who have contacted the agency directly about these issues, but FDA has compiled the information here to ensure that all IRBs are aware of and have access to it. When finalized, this guidance will supersede Question 56 in FDA’s January 1998 guidance Institutional Review Board Frequently Asked Questions – Information Sheet Guidance for Institutional Review Boards and Clinical Investigators.

The second draft guidance, Draft Guidance for Industry: Electronic Source Data in Clinical Investigations, provides guidance to sponsors, contract research organizations (CROs), data management centers, clinical investigators, and others involved in capturing, reviewing, and archiving electronic source data in FDA-regulated clinical investigations. This guidance revises and updates the draft guidance Electronic Source Documentation in Clinical Investigations. The draft guidance addresses source data (from clinical investigations) used to fill the predefined fields in an electronic case report form (eCRF), according to protocol , and discusses the following topics related to electronic source data: (1) identifying and specifying authorized source data originators; (2) creating data element identifiers to facilitate sponsors, FDA, and other authorized parties in examining the audit trail of data; (3) capturing source data into the eCRF using either manual or electronic capture methods; and (4) investigator responsibilities with respect to reviewing and retaining electronic data. Comments on both guidance documents will be accepted at www.regulations.gov until January 22, 2013.

FDA Draft Guidance Document on Transferring Clinical Investigation Oversight to Another IRB

This post was written by Erin Janssen.

The FDA has published a notice announcing the availability of draft guidance on "Considerations When Transferring Clinical Investigation Oversight to Another IRB." This guidance discusses the regulatory responsibilities of institutional review boards (IRBs), clinical investigators, and sponsors when oversight of a previously approved clinical investigation under FDA’s jurisdiction is transferred from one IRB to another IRB. This guidance also addresses questions previously raised concerning procedures and processes that are required and/or recommended by FDA when such oversight is transferred. Comments are due by August 13, 2012.

Older Entries

May 11, 2012 — FDA Final Rule on Disqualification of Clinical Investigators

March 14, 2012 — FDA Public Hearing Regarding Regulation of Clinical Trials (April 23-24)

February 13, 2012 — FDA Issues Guidance on New Informed Consent Requirements

December 29, 2011 — FDA Issues Draft Guidance Regarding Evaluation of Sex Differences in Medical Device Clinical Studies

November 14, 2011 — CMS Solicits Comments on Coverage with Evidence Development Framework

September 26, 2011 — Draft FDA Guidance on Exculpatory Language in Informed Consent

September 26, 2011 — FDA Guidance on Reproductive and Developmental Toxicities

September 1, 2011 — Comment Period Extended for Proposed Rule Regarding Human Subject Protections

September 1, 2011 — FDA Issues Draft Guidance Proposing Risk Based Approach to Oversight of Clinical Investigations

August 31, 2011 — HHS Issues Final Financial Conflict-of-Interest Rules for Researchers

August 16, 2011 — FDA Issues Draft Guidance Regarding Design of Pivotal Clinical Investigations for Medical Devices

July 26, 2011 — FDA Announces Open Registration for Clinical Investigator Training Course

June 14, 2011 — GAO Report on FDA Tracking of Pediatric Research

May 31, 2011 — FDA Publishes Draft Guidance on Financial Disclosures by Clinical Investigators

March 8, 2011 — Presidential Commission Seeks Input on Protection of Study Participants

March 7, 2011 — FDA Draft Guidance Documents: Electronic Data Sets for Pharmacoepidemiologic Studies, Pharmacogenomics/Premarketing Evaluation, REMS Medication Guides

January 13, 2011 — FDA Updates Informed Consent Regulations to Require Statement on Government Databank Disclosure

January 13, 2011 — FDA Issues Advanced Notice of New GLP Rules for Non-clinical Studies

January 13, 2011 — OIG Reports on Institutional Conflicts of Interest at NIH Grantees

January 13, 2011 — FDA Draft Guidance on Electronic Source Documents in Clinical Trials

December 15, 2010 — Guidance on Institutional Review Board (IRB) Approval and Continuing Review of Research

November 15, 2010 — FDA Issues Second Annual Report on Sponsor Compliance with Postmarketing Requirements

October 15, 2010 — Clinical Trial Compensation, Stem Cell Bills Signed Into Law

September 30, 2010 — HHS Guidance on Withdrawal of Subjects from Research

September 30, 2010 — FDA Issues Final Rule, Draft Guidance on Clinical Trial Safety Reporting Requirements

September 17, 2010 — FDA Draft Guidance on Occurrence of Suicidality in Clinical Trials

September 17, 2010 — FDA Public Workshop on Clinical Trials Involving Cell or Gene Therapy in Pediatric Populations (Nov. 2)

August 31, 2010 — GAO Report on New Drug Approvals Based on Non-Inferiority Trials

July 10, 2010 — FDA Monitoring and Inspection of Foreign Clinical Trials

July 7, 2010 — FDA Guidance on Frequently-Asked Questions for In Vitro Diagnostic Studies

July 7, 2010 — FDA Public Workshop on Development of Anti-Bacterial Drugs (Aug. 2-3, 2010)

May 27, 2010 — HHS Proposes Regulations on Financial Conflicts of Interest in Research

May 25, 2010 — IOM Recommendation for Greater FDA Authority on Post-market Surveillance

May 25, 2010 — FDA and NIH Launch Safety Reporting Website

March 15, 2010 — ICH Guidance on Non-Clinical Studies on Anti-Cancer Pharmaceuticals

March 15, 2010 — FDA Draft Guidance on Non-Inferiority Clinical Trials

March 15, 2010 — FDA Draft Guidance on Adaptive Design Clinical Trials for Drugs and Biologics

February 26, 2010 — FDA Proposed Rule on Reporting Information on Falsification of Data

February 12, 2010 — Draft Guidance on Continuing IRB Review after Clinical Investigation Approval

February 12, 2010 — Use of Bayesian Statistics in Medical Device Clinical Trials

February 12, 2010 — Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals

January 13, 2010 — Proposed Rule Amending Informed Consent Disclosure

December 21, 2009 — FDA Guidance on Use of Patient-Reported Outcome Measures to Support Labeling Claims

December 21, 2009 — Public Workshop on Clinical Trials (March 3-4, 2010)

December 4, 2009 — NIH Grantees' Financial Conflicts of Interest Policies

November 11, 2009 — Guidance on IRB Review of Clinical Research

November 11, 2009 — AHRQ Review of Impact of Payment Policy on Clinical Trials

October 30, 2009 — FDA Guidance Documents

October 30, 2009 — FDA Debarment and Disqualification Processes

September 23, 2009 — Promotion of Medical Products Using the Internet and Social Media

September 23, 2009 — FDA Guidance Documents

September 23, 2009 — Drug/Biologics Firm Performance Regarding Postmarketing Requirements

September 23, 2009 — Pediatric Clinical Trials Workshop

August 17, 2009 — FDA Issues Final Rules on Patient Access to Investigational Drugs

August 17, 2009 — FDA Targets Misconduct in Drug and Device Development

July 28, 2009 — FDA Guidance Documents & FAQs

June 23, 2009 — Clinical Trial Technology Assessment

May 7, 2009 — IOM Report on Conflicts of Interest in Medicine

April 24, 2009 — Routine Cost of Clinical Trials

March 24, 2009 — Congressional Institutional Review Board Hearing (March 26, 2009)

January 27, 2009 — Clinical Investigator Financial Disclosure

January 27, 2009 — Increasing Clinical Trial Enrollment; Comments Requested

January 27, 2009 — Certifications of Clinical Trial Registry/Results Submissions; Final Guidance

January 27, 2009 — Institutional Review Board Registration Requirements

January 16, 2009 — MedCAC Meeting on Medicare Coverage Evidence (March 18, 2009)

January 12, 2009 — FDA Proposes Guidance for Meeting Clinical Trial Registration Requirements

January 12, 2009 — AHRQ Study of Impact of Third-Party Payment on Clinical Trials

December 8, 2008 — Discontinuation of Human Subject Participation in Research.

October 28, 2008 — Guidance on Engagement of Institutions in HHS-Funded Human Subjects Research

October 7, 2008 — Medicare Routine Clinical Trial Costs

October 1, 2008 — Health Policy Legislation Moves Through Congress

September 10, 2008 — FDA Guidance: Bioequivalence (BE) Recommendations and Drug Clinical Trials