New York State's Proposal to Redefine Approval Processes for Advanced LDTs

On March 1, 2016, the New York State Department of Health - which has special rules that apply nationally to labs processing New York origin lab specimens - proposed a new "risk based policy" for LDT evaluation.

The home page for the effort is here.  The Agency accepted comment last spring, through April 29.

The full four page risk assessment proposal, as originally drafted for comment, is online here.

Tests that are LDTs will be quickly classified as low risk, moderate risk, or high risk "by CLRS staff."  Low risk LDts will will receive full approval and "validation will be reviewed as part of routine laboratory surveys."  Moderate risk LDTs will receive "conditional" review but this is discretionary on the judgment of staff.  High risk LDTs will not have the conditional approval option: they will need to complete a full CLRS review process before approval.

Although the PDF is the best reading format, I've clipped the text online, below the break.

One major stakeholder submitted a comment that test review times may now already take over a year and that this timeline could get worse due to understaffing and new rules.

NYSDOH Proposed Policy for 

Risk-based Evaluation of Laboratory Developed Tests (LDT)

March 2016

http://www.wadsworth.org/sites/default/files/WebDoc/308752912/Risk-based_LDT_Proposed%20Policy_3-10-16_final.pdf 

NYSDOH Wadsworth Center’s Clinical Laboratory Evaluation Program (CLEP) and its Clinical Laboratory Reference System (CLRS) scientific staff are proposing a three-tiered risk-based model for the review and approval of laboratory developed tests (LDT) to begin this year. This policy applies to laboratories holding a NYS clinical laboratory permit in the appropriate category of testing, and applies to all assays that require submission as directed in the Comprehensive Test Approval Policy and Submission Guidelines that can be found on our webpage at http://www.wadsworth.org/regulatory/clep/clinical-labs/obtain-permit/test-approval.

Features of the risk based evaluation process

1. All LDTs must be submitted to CLEP following the Test submission guidelines and include all the required materials. In addition, laboratories must address the four questions listed at the end of this document.

2. Assignment of risk into one of three classifications, high, moderate or low, will be made by CLRS scientific staff as part of the existing CLEP LDT validation review and approval process described on the CLEP Test Approval webpage.

3. Low risk LDTs will receive full approval and not be subject to review by CLRS staff, provided the laboratory holds a permit in the appropriate category of testing. Laboratories will be able to offer the test once notified by CLEP of the low risk designation. Validation will be reviewed as part of the routine laboratory surveys. However, we reserve the right to withhold approval and/or require review of the test at our discretion.

4. Moderate risk LDTs will receive Conditional Approval if the laboratory holds a permit in the appropriate category of testing. However, we reserve the right to withhold conditional approval at our discretion. Moderate risk LDTs still require review before full approval can be granted.

5. High risk LDTs will NOT receive Conditional Approval and will need to complete the CLRS review process before full approval will be granted. Review of High risk LDTs will be prioritized.

Definitions of terms used in risk classifications

• Well-established: the methodology and indications for use have been previously approved by the FDA and/or have been described in multiple peer-reviewed publications, and have been used by multiple laboratories as described without any modifications.
• Key determinant: the test result provides critical or essential information to 1) diagnose or 2) indicate a greater likelihood of developing a disease or condition, and/or indicates eligibility for a specific treatment.
• Impact: the extent to which the result could have an impact on the patient’s morbidity, mortality or condition if the result were not accurate. An LDT will have a high impact if an analytically or clinically inaccurate result leads to erroneous diagnosis and/or prediction of an inappropriate treatment, thereby increasing the morbidity or even cause death.

LDT Risk Classifications (see also flow diagram below)

• Low Risk LDT:
o An LDT that uses a well-established methodology, does not provide critical or essential information (key determinant) about a serious or life-threatening disease, disorder or condition, and an inaccurate result is not likely to lead to increased morbidity or mortality (low impact).

• Moderate Risk LDT:
o An LDT that uses a well-established methodology and provides critical or essential information (key determinant) about a serious or life-threatening disease, disorder or condition, whether or not the reported result, if inaccurate, could be used to support an incorrect diagnosis and/or an inappropriate clinical treatment that is likely to result in serious morbidity or mortality (high impact), or
o An LDT that uses methodology that is well-established, does not provide critical or essential information (key determinant) about a serious or life-threatening disease, disorder or condition, but the reported result, if inaccurate, could be used to support an incorrect diagnosis and/or an inappropriate clinical treatment that is likely to result in serious morbidity or mortality (high impact)
o An LDT that uses a methodology that is not well-established, but is not considered a key determinant and an inaccurate reported result is not likely to lead to increased morbidity or mortality (low impact).
• High Risk LDT:
o An LDT that uses methodology that is not well-established and provides critical or essential information (key determinant) about a serious or life-threatening disease, disorder or condition, whether or not the reported result, if inaccurate, could be used to support an incorrect diagnosis and/or an inappropriate clinical treatment that is likely to result in serious morbidity or mortality (high impact), or
o An LDT that uses methodology that is not well-established, does not provide critical or essential information (key determinant) about a serious or life-threatening disease, disorder or condition, but the reported result, if inaccurate, could be used to support an incorrect diagnosis and/or an inappropriate clinical treatment that is likely to result in serious morbidity or mortality (high impact).

Questions that will be used to inform risk classification

1. Does the LDT utilize a well-established methodology? If so provide supporting evidence e.g. references, and/or if available FDA approval/clearance/exemption.
2. Was the intended clinical use or claim for the LDT established via literature, clinical trial, or both? Supporting clinical data and/or publications must be included in the submission package.
3. Briefly explain why this LDT does, or does not, provide critical or essential information to 1) diagnose or 2) indicate a greater likelihood of developing a disease or condition, and/or indicate eligibility for a specific treatment.
4. Briefly describe the potential impact of an inaccurate test result.