CMS Proposes Clinical Trial Coverage Policy

Background

July 26, 2007 - In 2000 the Centers for Medicare and Medicaid Services (CMS) published the Clinical Trial Policy (CTP) National Coverage Determination (NCD) in response to a Presidential Executive Memorandum concerning payment for routine costs incurred by Medicare beneficiaries participating in clinical trials.

In July 2006, CMS began a reconsideration of that 2000 NCD to address several issues about the policy. A proposed decision memorandum was released for public comment in April 2007. On July 9, 2007, CMS released a final decision memorandum on this proposed document. This document finalized policy on two issues while remaining silent on the vast majority of policies proposed in the April 2007 proposed memorandum.

On July 19, 2007, CMS released another proposed decision memo, “Proposed Decision Memo for Clinical Trial Policy (CAG-0071R2)”, as a reconsideration of the CTP which has been renamed Clinical Research Policy (CRP). This proposal addresses many of the issues that were included in the original April 2007 proposed policy document, but were not finalized in the July 9, 2007 final decision memorandum.

The proposed decision memo that was released on July 19, 2007, is open for public comments. Comments are due to CMS on August 19, 2007.

Issues to Consider

While addressing similar issues as the original proposed decision memo, CMS has stated that their intention with the new document is to clarify questions that were raised in the public comments received in response to the April 2007 proposed decision memo. In assessing the impact of this policy on hematology/oncology related research, we propose you consider the following questions:

1. Is the definition of research broad enough to encompass research conducted by your specialty?
   
   
2. Are the burdens of the standards fair and reasonable? Does meeting the standards cause an undue burden?
   
   
3. Are appropriate studies excluded from the standards? Should there be additional studies excluded?
   
   
4. Is the definition of covered services fair and reasonable? Does it provide for coverage of expected items and services?
   
   
5. What is the burden level of the approval process? Does it seem fair and reasonable?

Brief Summary

A brief summary that highlights relevant issues follows.

1. Is the definition of research broad enough to encompass research conducted by your specialty?

CMS has proposed the following definition of clinical research: “…any systematic investigation involving human participants which is designed to contribute to generalizable knowledge and which involves a clinical intervention, care delivery strategy, or diagnostic technique designed to potentially improve predefined health outcomes.”

2. Are the burdens of the standards fair and reasonable? Does meeting the standards cause an undue burden?

CMS is proposing a set of standards for clinical research studies. These standards were created with input from other Federal Agencies that conduct clinical research, the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) and the Agency for Healthcare Research and Quality (AHRQ). They cover a wide range of issues from the intent of the research, research-protocol-related issues and compliance with Federal regulations.

Standards worth noting and considering their level of burden and overall feasibility include:

• Publication of results: The research study protocol specifies the method and timing of public release of all pre-specified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early. The results must be made public within 24 months of the end of data collection. If a report is planned to be published in a peer-reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors. However, a full report of the outcomes must be made public no later than three years after the end of data collection.
  
  
• How protocol relates to subpopulations: The research study protocol must explicitly discuss subpopulations affected by the treatment under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria affect enrollment of these populations, and a plan for the retention and reporting of said populations on the trial. If the inclusion and exclusion criteria are expected to have a negative effect on the recruitment or retention of underrepresented populations, the protocol must discuss why these criteria are necessary.
  
  
• How results are generalizable to the Medicare population: The research study protocol explicitly discusses how the results are or are not expected to be generalizable to the Medicare population to infer whether Medicare patients may benefit from the intervention. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability or Medicaid eligibility.

The complete list of standards can be found below in Appendix A.

3. Are appropriate studies excluded from the standards? Should there be additional studies excluded?

CMS is proposing to exclude certain studies from the standards requirement. Studies that would be excluded include data collection processes, that while are by definition clinical research, are based upon previously collected data, or data collected in such a manner as to not influence current patient management or health outcomes. These studies would have no pre-specified interventions. CMS has provided the following examples:

• Simple non-comparative case reports an case series
  
  
• Retrospective studies that evaluate events that have already occurred including studies that rely exclusively on previously collected administrative records, medical data, or other available data
  
  
• Quality assessment, quality improvement, or performance improvement studies
  
  
• Prospective studies in which natural human behavior is observed in a way that does not intentionally or unintentionally change or potentially change the behavior of patients or providers
  
  

4. Is the definition of covered services fair and reasonable? Does it provide for coverage of expected items and services?

In the original policy CMS provided for coverage of “routine costs” under a clinical trial. CMS is now proposing to adopt the term “usual patient care.” CMS has proposed the following definition for usual patient care:

“Usual patient care includes routine clinical services and investigational clinical services in clinical research when the investigational clinical services would be covered outside of the clinical research and the clinical research meets the standards for a clinical research study outlined in this policy.”

CMS has also proposed the following coverage determination:

“Medicare covers usual patient care in qualified clinical research. Medicare does not cover usual patient care when such care is provided free to the Medicare beneficiary or when the study sponsor agreement with investigator sites or the informed consent documents provided to the patient specify that the care will be provided free to participants “

5. What is the burden level of the approval process? Does it seem fair and reasonable?

In the 2000 policy CMS listed two processes for approving studies: deeming and self certification. Deeming allowed other Federal Agencies to deem that standards had been met. The self certification process was never developed.

In this proposed policy CMS dismissed self certification and using the Institutional Review Board (IRB) process, both which were proposed in public comments, as potential options for an approval process. Instead CMS has proposed the following approval process for studies:

• Study sponsor/principal investigator has certified to CMS that the standards in this policy have been met by sending a letter with the following information:
  
  • Name of research study
  • ClinicalTrials.gov registry number
  • Study start date
  • A point of contact with telephone number
  • Discussion as to how the study meets each of the standards in this policy
    
    
• CMS will announce the approval process by posting it on ClinicalTrials.gov
  
  
• Providers will add information to claim forms indicating that this study has met the standards of the policy as outlined by CMS

In considering the implementation of the approval process, questions that come to mind include not only the burden level on the investigator but the capacity and resources at CMS to process these requests in a timely manner.

Other Miscellaneous Issues

The proposed policy also addressed several other related miscellaneous issues.

• Local coverage determinations: Items and services provided with clinical research studies are subject to local policies including local coverage determinations (LCDs).
• Investigational Device Exemption (IDE): This policy does not alter previous policies related to IDEs.
• Transition period: This policy will not impact any clinical studies that was covered under a previous policy and that has begun enrollment.
• Humanitarian Device (HUD) exemptions: Local contractors will continue to make coverage determinations related to HUD.

Further Information
The complete proposed policy is posted on the CMS Web site.

APPENDIX A

Proposed Decision Memo for Clinical Trial Policy (CAG-0071R2)

Standards for clinical research to support Medicare coverage of items and services

Medicare will cover items and services furnished through clinical research only when the following standards are met:

• The principal purpose of the research study is to test whether a particular intervention potentially improves the participants’ health outcomes.
  
  
• The research study is well-supported by available scientific and medical information or it is intended to clarify or establish the health outcomes of interventions already in common clinical use.
  
  
• The research study does not unjustifiably duplicate existing studies.
  
  
• The research study design is appropriate to answer the research question being asked in the study.
  
  
• The research study is sponsored by an organization or individual capable of executing the proposed study successfully.
  
  
• The research study is in compliance with all applicable Federal regulations concerning the protection of human subjects found at 45 CFR Part 46. If a study is FDA-regulated, it also must be in compliance with 21 CFR Parts 50 and 56.
  
  
• All aspects of the research study are conducted according to the appropriate standards of scientific integrity.
  
  
• The research study has a written protocol that clearly addresses, or incorporates by reference, the Medicare standards.
  
  
• The clinical research study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals. Studies of all medical technologies measuring therapeutic outcomes as one of the objectives meet this standard only if the disease or condition being studied is life-threatening as defined in 21 CFR 312.81(a) and the patient has no other viable treatment options.
  
  
• The clinical research study is registered on the ClinicalTrials.gov website by the study sponsor/principal investigator prior to the enrollment of the first study subject.
  
  
• The research study protocol specifies the method and timing of public release of all pre-specified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early. The results must be made public within 24 months of the end of data collection. If a report is planned to be published in a peer-reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors. However, a full report of the outcomes must be made public no later than three years after the end of data collection.
  
  
• The research study protocol must explicitly discuss subpopulations affected by the treatment under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria affect enrollment of these populations, and a plan for the retention and reporting of said populations on the trial. If the inclusion and exclusion criteria are expected to have a negative effect on the recruitment or retention of underrepresented populations, the protocol must discuss why these criteria are necessary.

• The research study protocol explicitly discusses how the results are or are not expected to be generalizable to the Medicare population to infer whether Medicare patients may benefit from the intervention. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability, or Medicaid eligibility.