International Consortium for Harmonization of Clinical Laboratory Results. Operating Procedures

Transcription

1 International Consortium for Harmonization of Clinical Laboratory Results Operating Procedures Approved: February 11, 2014

2 Background Results from clinical laboratory measurement procedures should be comparable irrespective of the laboratory, method or time when measurements are made. Comparable results are necessary to allow meaningful interpretation of a patient s condition over time, to allow clinical practice guidelines to be implemented, to allow data from clinical research to be used to develop guidelines, and for results to be aggregated into electronic health records. A lack of recognition that results are neither standardized nor harmonized may lead to erroneous clinical, financial, regulatory, or technical decisions. To address these problems, an international conference recommended that an international infrastructure be developed to provide: a systematic approach for prioritization of measurands to be harmonized based on medical importance and the technical feasibility to achieve harmonization; an information portal on global harmonization activities to avoid duplication of effort; and procedures to implement harmonization for measurands for which no reference measurement procedure was likely to be developed. (Roadmap for harmonization of clinical laboratory measurement procedures. Clinical Chemistry 2011;57: ) Mission Provide a centralized process to organize global efforts to achieve harmonization of clinical laboratory test results. Scope Provide a global infrastructure to prioritize, organize and manage harmonization of clinical laboratory results which will optimize public health activities and patient care. These activities will eliminate duplication of effort and maximize resource utilization. The infrastructure includes: A systematic process that will allow the prioritization and organization of work, on a global scale, for those measurands that are the most medically important and technically feasible for harmonization. Processes for harmonization of a measurand when no reference measurement procedure is available. Work products for harmonization that will be listed by the Joint Committee on Traceability in Laboratory Medicine (JCTLM) permitting IVD manufacturers to meet various traceability requirements for regulatory purposes. A website that will serve as a resource for information on global activities to harmonize or standardize clinical laboratory measurement procedures. 2 P age

3 Value proposition Clinical practice guidelines frequently base diagnostic and therapeutic decisions on laboratory test results. Such clinical decisions will be compromised, leading to erroneous clinical, financial, regulatory, or technical decisions, if the test results are not consistent among different measurement procedures, laboratories and times of measurement. Although several organizations are addressing harmonization of test results, there is no global organizational oversight to inform decisions on prioritization and to ensure resources and technical solutions are optimally applied. This international consortium will provide oversight for prioritization of the medical importance of measurands for harmonization, information on the technical feasibility to achieve harmonization, coordination of harmonization activities, and management of specific technical processes to achieve harmonization of a measurand. Implementation of the infrastructure for a harmonization process will require the involvement and cooperation of international clinical laboratory and medical organizations, IVD manufacturers, metrology institutes, standard-setting organizations, public health organizations and regulatory agencies. Structure and Operational Overview International Consortium for Harmonization of Clinical Laboratory Results Strategic Partners Group Council Harmonization Oversight Group Harmonization Implementation Groups Special Working Groups Secretariat/Host - AACC The International Consortium for Harmonization of Clinical Laboratory Results (ICHCLR) will be a hosted by the AACC which will serve as the Secretariat. As the Secretariat/host organization, the AACC will manage all administrative, finance, accounting, and marketing services for a fee. The AACC will also 3 P age

4 provide liability protection and tax exempt status, and will serve as the title-holding entity in all matters regarding the ICHCLR (intellectual property rights copyrights, trademarks, patents, etc.). The Consortium will be governed by a Council whose members represent organizations that contribute at an annual financial level defined by the Council to support the core administrative functions of the program. The Council will be responsible for the fiduciary and administrative oversight of the consortium. The Council will be responsible for determining the scope of operations of the ICHCLR within a budget approved by the AACC. Stakeholders who are committed to harmonization of clinical laboratory results (e.g. clinical laboratory and medical organizations, IVD manufacturers, metrology institutes, standard-setting organizations, public health organizations, regulatory agencies and individuals) may become members of the Strategic Partners Group (SPG). The SPG supports the program by submitting measurands in need of harmonization, nominating experts for consideration to serve on the Harmonization Oversight Group (HOG), and reviewing and commenting on harmonization project plans and milestone updates from Harmonization Implementation Groups (HIGs). Council members are also members of the Strategic Partners Group. The Harmonization Oversight Group (HOG) is the body responsible for organization and coordination of the harmonization process. The HOG will proactively communicate with stakeholders to provide updates on harmonization activities and to solicit input from them on relevant activities in their organizations. The HOG will establish and maintain a web site to coordinate information about harmonization activities. The HOG will review measurand submissions. In most cases, a Special Working Group (SWG) of experts in a particular measurand will be appointed to review the data and make a recommendation to the HOG. The HOG will assign a medical importance classification, and provide information on the technical feasibility to achieve harmonization for a measurand. The HOG will cooperate with other organizations to coordinate harmonization work. When a reference measurement procedure can be developed, the HOG will preferentially refer the harmonization activity to an organization with expertise in such work. For harmonization of a particular measurand to be managed by the HOG, a Harmonization Implementation Group (HIG) will be formed, funding obtained and the HIG given responsibility to organize and conduct the harmonization activity. Funding Members of the Council will fund the adminsitrative costs of the program with an annual contribution of $50,000 (subject to annual review) per member per year. Members of the Strategic Partners Group will be assessed a fee of $500 (subject to annual review) per year. Financial support for harmonization of a specific measurand, under the direction of a HIG, will be obtained from interested stakeholders by the HOG in advance of initiating a specific project. 4 P age

5 The work products, e.g. reference materials, of HIGs may generate revenue as the program progresses. Such revenue will go to a general fund to offset operating expenses or to be reinvested in other harmonization projects. Detailed Operational Procedures for the Harmonization Oversight Group Table of Contents 1. Definitions 2. Abbreviations 3. Harmonization Oversight Group 4. Special Working Group 5. Harmonization Implementation Group 6. Funding for harmonization of a specific measurand 7. Acceptance of new harmonization materials and/or procedures for a measurand 8. Revision of Operational Procedures for the Harmonization Oversight Group 9. Policies 10. Forms 5 P age

6 1. Definitions A. Essential terms: Harmonization A process that achieves uniform results among measurement procedures when no reference measurement procedure exists. Standardization - A process that achieves uniform results among measurement procedures based on calibration traceability to Système International d'unités (SI; International System of Units) using a reference measurement procedure. NOTE: the term harmonization is used in this document to refer to either harmonization or standardization as applicable. B. Other terms: Higher-order reference measurement procedure a measurement procedure that is highly specific for a measurand, thoroughly validated, and whose calibration is directly traceable to SI using a primary reference material or the measurement procedure itself defines the SI. Industry - an organization that manufactures and/or distributes materials used in clinical laboratory testing. For example, industry includes manufacturers or distributors of instruments, reagents, cell lines, calibrators, controls, reference materials, proficiency testing or external quality assessment programs. Note that reference materials may also be provided by metrology organizations and proficiency testing or external quality assessment programs may also be provided by public health or professional organizations. Measurand the quantity intended to be measured. Specification of a measurand includes the specific molecular form or species that is measured as well as the matrix in which that molecule is contained. Note the term analyte (component represented in the name of a measurable quantity) is sometimes used when measurand is intended. Primary reference material a pure substance with a certificate of analysis that describes its purity and the molecular form of the substance. Secondary reference material a material, frequently in the matrix of the clinical samples intended to be measured, which has its value assigned by measurement or by a consensus process. Stakeholder - any individual or entity with an interest in harmonization of clinical laboratory results including: clinical practice groups, laboratory practice groups, in-vitro diagnostics manufacturers, public health organizations, metrology institutes, standards development organizations, regulatory organizations, proficiency testing or external quality assessment providers. 6 P age

7 2. Abbreviations GMT Greenwich Mean Time HOG Harmonization Oversight Group HIG Harmonization Implementation Group ISO International Organization for Standardization IVD In-Vitro Diagnostics JCTLM Joint Committee for Traceability in Laboratory Medicine NIST National Institute for Standards and Technology (USA) PT/EQA Proficiency Testing/ External Quality Assessment RMP Reference Measurement Procedure SI Système International d'unités (International System of Units) SWG - Special Working Group 3. Harmonization Oversight Group (HOG) The HOG is the body responsible for organization and coordination of the harmonization process. The HOG provides oversight for prioritization of measurands for harmonization, for organizing and disseminating information on global activities for harmonization of clinical laboratory measurement procedures, and for either referring work to another organization or managing a harmonization effort for a specific measurand. Figure 1 shows an organizational diagram for HOG operation. 7 P age

8 3.2 Stakeholders (Strategic Partners Group): Clinical practice groups Metrology Institutes Laboratory practice groups Standards organizations IVD manufacturers Regulatory organizations Public health organizations PT/EQA organizations / Coordination / Cooperation If work is underway, refer to that group If RMP is possible, refer to another group 3 Harmonization Oversight Group Communication Operation 3.3 Evaluate measurand proposals When no RMP / 6 Solicit champion and funding Clinically affected entity Economically affected entity / / 4 Special Working Group Review priority and technical feasibility Recommendation to Harmonization Oversight Group / 5 Harmonization Implementation Group Technical plan Surveillance plan Implement the plans Achieve JCTLM listing Figure 1. Organizational diagram for HOG operation. Numbers refer to sections in this document. Adapted from: Roadmap for harmonization of clinical laboratory measurement procedures; Clinical Chemistry 2011; 57: P age

9 The responsibilities of the HOG include: Communicating with the SPG for submission of measurands for consideration and reporting the status of harmonization for measurands. Decisions on the classification of medical importance for harmonizing a measurand based on input from a SWG. Decisions on the technical feasibility of harmonization based on input from a SWG. Creation and oversight of SWGs. Obtaining and providing information on the status of harmonization for measurands already being addressed, either within ICHCLR or by a cooperating organization. Cooperating with other organizations with expertise and interest to develop a reference measurement procedure or a strong interest in a particular measurand, and providing information on the status and a link to the organization addressing such a measurand. Creating a HIG and soliciting funding to develop and execute a harmonization plan for a high priority measurand for which no other organization is able to accept the task. Review progress of HIGs on a regular basis and provide feedback. Review and approve work products of HIGs prior to final implementation. Submission of approved work products of HIGs to the Joint Committee for Traceability in Laboratory Medicine (JCTLM) for review and listing. Communication of harmonization issues and technical advances to regulatory bodies. Dissemination of information on the status of harmonization activities being conducted by this or other organizations to avoid duplication of effort. Develop and coordinate collaborations and development of resources needed to support and promote harmonization in laboratory medicine. The HOG should meet at least annually (it is anticipated that an annual meeting will be face to face for at least the first 3 years). Virtual meetings will be preferred for most business, to minimize costs and to facilitate global participation. The HOG will issue an annual report, posted on the web site, describing the scientific and business status of its harmonization activities. The Council has the responsibility for oversight of the HOG. 3.1 HOG membership The HOG typically has 8 members. New members of the HOG will be selected by the Council from individuals nominated by the SPG. The Council is responsible to ensure that the HOG membership represents a broad range of existing and emerging technologies and disciplines. Appointments will be for 3 years on a calendar year starting January 1 (GMT -5) and ending December 31 (GMT-5). An individual may be reappointed for 1 additional 3 year term. The composition will include 2 members from industry (nominated by an industry or by an industry related SPG), 2 from non-industry organizations (nominated by an organization SPG) and 4 ad-hoc members based on expertise (nominated by any SPG). Four of the inaugural HOG members will serve initial 2 year terms to introduce stagger. The initial HOG terms will end December 31, 2015 (two year terms) or December 31, 2016 (three year terms). Nominators must provide a CV of the nominee and describe the expertise and experience of the individual with regard to harmonization development activities. Selection of HOG members should consider the 9 P age

10 desirability of having a mix of senior and junior scientists who have demonstrated expertise in individual harmonization projects to ensure the sustainability of the harmonization program. A HOG member s duty will be to the HOG and not to be a representative of the particular SPG that made the nomination. HOG members will not represent a specific industry or organization but will ensure that the general perspective of industry and organizations is represented. All HOG members shall disclose (see Section 3.2) financial or other interests that may be perceived to have the potential to impact their ability to offer an unbiased view of matters that may come before the HOG. The HOG chair will be selected by the Council and must have a minimum of one year service as a HOG member to be eligible for chair. A vice-chair will also be selected by the Council and this person must be on a different term rotation schedule than the chair. The vice-chair will serve in a deputy role, but will not automatically be in line to become the next chair. Qualifications to be a HOG member: Breadth of experience in harmonization activity Experience in consensus committee work Commitment to the time necessary to fulfill the role (approximately 2 days per month plus an annual face-to-face meeting) 3.2 Communication with the Strategic Partners Group (stakeholders). The HOG will communicate with the SPG to provide updates on harmonization and to solicit input on relevant activities in their organizations. The HOG will establish and maintain a web site to coordinate information about harmonization activities. The web site will provide information on: the status of harmonization of measurands; organizations working to harmonize measurands; literature resources related to harmonization of measurement procedures; recommendations related to implementing harmonization of measurands, documenting such harmonization, and informing end users of the calibration traceability of measurement procedures for a particular measurand; and other information of interest to stakeholders as may be determined by the HOG. The web site will also provide an on-line process for submission of candidate measurands to be prioritized for harmonization. 3.3 Evaluation of measurands submitted for harmonization The HOG will review measurand submissions and determine if harmonization is likely to be medically important and technically feasible. The HOG will assign a medical importance classification and it will recommend that a medically important measurand be harmonized if it is technically feasible to do so. If it is not technically feasible to achieve harmonization, the medical importance will be unchanged and the measurand will be reviewed periodically for any change in feasibility Appoint a Special Working Group (SWG; see Section 4) If needed, the HOG will appoint a SWG to review available information (provided by the submitter of a measurand for consideration, obtained from available literature, or by solicitation from experts in the field) on a given measurand. The SWG will make a recommendation on the medical importance of harmonization, the technical feasibility for harmonization, and the gap between what is known about calibration for a measurand and what is determined to be needed to proceed with harmonization. 10 P age

11 3.3.3 Establish medical importance and technical feasibility for harmonization The HOG will establish the medical importance for harmonization of a measurand. Medical importance should have categories (e.g. high, medium, low) rather than a numerical ranking. The technical feasibility to achieve harmonization will be evaluated separately from medical importance. The categories will enable medically important analytes to be addressed based on the technical feasibility of achieving harmonization and the ability to raise funds. A list of measurands indicating medical importance will be maintained on the harmonization.net web site along with a summary of justifications for the medical importance and technical feasibility. The list will be reviewed periodically to determine if a change in classification for measurands is appropriate Appeal of a medical importance or technical feasibility decision An appeal for reconsideration may be made in writing to the HOG within 60 days of posting a medical importance or technical feasibility decision. The HOG and the SWG will review the evidence and respond to the appeal within 60 days Referral to other groups for harmonization of a given measurand In the event a submitted measurand is already being addressed by another organization, or an organization has expressed interest in harmonizing a specific measurand, the HOG will typically refer the work to that group unless the HOG determines there is a technical limitation in the approach being developed or used. The HOG will maintain communication with that group in order to report the status of the project via the harmonization.net website. 3.4 Establishing a harmonization activity for a measurand Measurands suitable for development of a reference measurement procedure (standardization) When the SWG determines that a reference measurement procedure is feasible and should be developed, the HOG will preferentially refer the standardization work to a group with experience in standardization and which expresses interest in the project. The HOG will maintain communication with that group in order to report the status of the project via the harmonization.net website. In the event no other group is available to standardize the measurand, the HOG may seek funding and create a HIG to standardize the measurand Measurands for which no reference measurement procedure is likely to be developed For a measurand that will have a harmonization program developed, the HOG will appoint a HIG (see Section 5) with initial responsibility for developing a harmonization project proposal. 11 P age

12 Based on the project proposal, the HOG and HIG will jointly solicit financial support for the harmonization activity. Once financial support is available, the HIG will be charged to undertake the harmonization activity. 3.5 Checklist maintenance The checklists and report formats used for measurand submission and evaluation are maintained by the HOG who may seek assistance from a SWG in maintaining the checklists. 4. Special Working Group (SWG) When needed, the HOG will create an ad-hoc Special Working Group to review available information and to determine if any other group is addressing that measurand. The SWG will provide a report to the HOG that addresses: the medical importance for harmonization, the technical feasibility for harmonization, and the gap between what is known about calibration for a measurand and what is determined to be needed to proceed with harmonization. The SWG will be dissolved upon submission of a report to the HOG. A SWG will typically include 4-6 members with expertise in the clinical use and laboratory measurement of the measurand. The HOG will appoint members based on nominations included with the submission of a measurand and on solicitation of candidates from colleagues. Potential members will be asked to commit the time necessary for the work (approximately 1 day per week for 3 months). The HOG will appoint one member to be chair of the SWG. Deliberations regarding the members for a SWG will be confidential. 4.1 Special Working Group (SWG) Operation The submitter of a request to harmonize a measurand will provide information using a structured submission checklist. The SWG will use this list as well as additional published or proprietary information, and expert opinion, to assist in the assessment. The SWG will not conduct original investigations to obtain missing information but may make a recommendation to the HOG that such information is needed to make a final determination of medical importance or technical feasibility for harmonization. The goal for the SWG is to assemble and evaluate information related to the need for and feasibility of harmonization, and report to the HOG in 3 months. The SWG will conduct meetings by electronic means Evaluation of medical importance for harmonization Medical importance will be based primarily on the impact on patient care of a lack of harmonized test results. Structured checklists will be used to evaluate the available information and to identify missing information Evaluation of technical feasibility of achieving harmonization Feasibility to achieve harmonization will be evaluated separately from medical importance. Feasibility will be evaluated based on available technical information using a structured checklist. 12 P age

13 4.1.3 Report of recommendations The SWG will issue a report of its findings using a structured format. The report will also include identification of missing information that is needed, or would be useful, to assess medical importance or technical feasibility, and suggestions for membership in a HIG that may be formed for that measurand. The SWG report and the final classification of medical importance and assessment of technical feasibility by the HOG with explanation will be posted to the harmonization.net web site. 5. Harmonization Implementation Group (HIG) For a measurand that is selected to have a harmonization program developed, the HOG will create a Harmonization Implementation Group with responsibility for developing and executing the program. The HOG will appoint members based on nominations included with the submission of a measurand, recommendations from the SWG for that measurand, and/or other experts in the clinical use and laboratory measurement of the measurand. In addition, potential members will be asked to confirm that they are able to commit the necessary time for the work. The HOG will appoint one member to be chair of the HIG. Deliberations regarding the members for a HIG will be kept confidential. 5.1 A Harmonization Implementation Group A HIG will consist of up to 10 members with an appropriate mix of expertise to accomplish harmonization for a measurand. The membership must include at least 1 industry professional, 1 clinical practitioner, 1 clinical laboratory professional and 1 member with expertise in implementing harmonization protocols (who may be one of the already named members). A HOG member will serve as a liaison to the HIG. The initial responsibility of the HIG is to develop a draft protocol that includes a technical approach, an estimated timeline and cost to achieve harmonization for a specific measurand. The draft protocol will be used to help solicit funding. The initial work of the HIG will be conducted by electronic communication. Once the harmonization project is initiated, it is anticipated that face-to-face meetings as well as teleconferences will be needed and these expenses will be included in the initial budget estimate. The initial draft protocol should be delivered to the HOG within 3 months. The HIG does not have authority to enter into any financial or contractual arrangements. The Council is responsible to approve any financial arrangements with another group involved in a harmonization activity. Once funding for the harmonization of a measurand is obtained, the HIG will initiate the harmonization activity and manage it to completion. In the event a HIG member resigns, the HIG chair and the HOG will determine who, if anyone, will replace the member Affiliate members of a HIG 13 P age

14 Any interested individual may become an affiliate member of a HIG. Affiliate membership provides a mechanism for interested stakeholders to be informed of progress and to have an opportunity to provide input as the harmonization activity progresses. In general, affiliate members will not be permitted to participate in conference call meetings of a HIG. This restriction on conference call meetings is intended to control cost and to ensure good productivity at the meetings. At the discretion of the HIG chair, one or more guests with special expertise may be invited, as needed, to a particular conference call meeting of the HIG. Transparency will be maintained by providing minutes of meetings to affiliate members and allowing them to submit written comments that will be responded to in writing by the HIG. All minutes, comments and responses will be posted to the harmonization.net web site to ensure transparency and inclusiveness of the process. Open face-to-face meetings of a HIG may be scheduled to enable general review of a harmonization project, to permit dialog with stakeholders regarding resolution of issues or to reach consensus on technical matters. Affiliate members may attend open meetings at their own expense as long as adequate space is available HIG responsibilities The HIG will be responsible for organizing and executing harmonization of measurement procedures for a measurand to include: Assessment of the current status of harmonization Development of a harmonization protocol Development of any needed components such as reference materials, value assignment process, harmonization processes, etc. Organize and implement the harmonization process. It is desirable to include all interested providers of measurement procedures for the measurand in an implementation process. Publication of results. Organization of a submission to obtain JCTLM listing for the harmonization process to include any reference materials or measurement procedures that may be included The submission to JCTLM will be made by the HOG. Creation of a surveillance program for the measurand which will typically be in collaboration with EQA providers. Preparation of an annual report on the status of harmonization for a measurand 5.2 HOG oversight of a HIG for a specific measurand The HOG will ensure that a HIG makes sustained progress on the harmonization activity. The HIG chair will submit a written report to the HOG, at least annually, on the status of a harmonization project and the proposed activity for the next year(s). The report, with any comments from the HOG, will be posted to the harmonization.net web site. In addition, the HOG liaison must be copied into all project related correspondence between HIG members and will also receive an update on progress at regular intervals. 14 P age

15 If the HOG determines that there has been inadequate progress, it may replace the chair or revise the membership of the HIG. In the event a HIG member is removed from the project, the HIG chair and the HOG will determine who, if anyone, will replace the member. In the event the HIG chair is removed, the HOG, with advice from remaining HIG members, will determine who will be appointed as the new chair Termination of a measurand harmonization activity If it is found that there are one or more insurmountable barriers to harmonization of a measurand, the HOG may terminate a project. The priority may remain unchanged and a measurand will be reconsidered for harmonization in the future. The HOG may terminate a project if inadequate progress is being made to achieve harmonization, or if the medical importance changes due to changes in clinical practice. 6. Funding for a HIG for harmonization of a measurand An essential component of this harmonization program is to ensure adequate financial support for a harmonization project. Financial support for harmonization of a specific measurand will be obtained in advance of initiating a project. A potential funder will be able to make an informed decision regarding support based upon the HOG setting out, in advance of solicitation, criteria for priority and feasibility assessment, an experimental approach for harmonization, a timeline and cost estimates, and assurance of transparency of operation. The HOG will solicit support from potentially interested parties including but not limited to: IVD manufacturers, pharmaceutical manufacturers, and other providers of health care products and services that depend on laboratory measurements for a particular measurand to provide quality patient care. 7. Review and approval of materials and/or procedures to accomplish harmonization for a measurand 7.1 Approval process Work products of a HIG will be approved by the HOG. The HIG will prepare documentation that validates their work. Documentation will typically include a peer reviewed publication. 7.2 Submission to JCTLM Once approved by the HOG, a new reference material or procedure for harmonization of a given measurand will be submitted by the HOG to JCTLM for review and listing. 8. Revision of Operational Procedures for the Harmonization Oversight Group 15 P age

16 Revisions to these Operational Procedures may be proposed by the HOG or the Council and accepted if approved by a majority vote of the Council. 9. Policies 9.1 Policy on transparency of proceedings and potential conflicts of interest It is important that the International Consortium for Harmonization of Clinical Laboratory Results is open and transparent with its discussions and decisions on all matters relating to its harmonization activities. Such activities should not be inhibited by undeclared conflicts of interest. Therefore, each participant in a harmonization activity of this organization shall be required to read and sign the conflict of interest policy and disclosure statement. The disclosure statement shall be signed annually by all members of the program s units or sub-units. A conflict of interest does not automatically exclude participation. However, since openness and transparency are important to the harmonization process, it is the duty of each individual to declare the possibility of any potential conflict of interest on each occasion when it may occur. If necessary, the HOG or the Council will determine if a potential conflict is sufficient to preclude any individual from participation. 9.2 Policy on cooperation with other organizations The International Consortium for Harmonization of Clinical Laboratory Results recognizes that global harmonization of results cannot be accomplished by a single organization. Consequently, our policy is to foster cooperative working relationships with all interested stakeholders, and thus avoid duplicative activities and enable optimal use of available resources to achieve the goal of harmonized clinical laboratory results. 9.3 Policy on confidential or proprietary information Confidentiality agreements may be executed if needed to consider confidential or proprietary information relevant to a measurand s evaluation for medical importance or technical feasibility, or to implement a harmonization activity. 16 P age