- Email: [email protected]
Guidelines for the review of pathology in the research context
Guidelines for the review of pathology in the research context Maire A. Duggan, MD, FRCPC,a Rashmi Goswami, MD, FRCPC,b Antony M. Magliocco, MD, FRCPC,c Miguel Burnier, MD, PhD,d and Davinder Sidhu, MD, LLB,a on behalf of the Canadian Association of Pathologists (Association Canadienne des Pathologistes) Working Group, Calgary, Alberta, Toronto, Ontario, and Montreal, Quebec, Canada, and Tampa, FL
Background. Research involving a retrospective review of a patient’s pathology could change the original pathologist’s diagnosis and alter management, treatment, and prognosis. In the interests of patient safety, this review diagnosis needs to be validated and the impact on patient care assessed before disclosure to the patient occurs. The Canadian Association of Pathologists-Association Canadienne des Pathologistes (CAP-ACP) did not have a guideline for managing this scenario. Methods. Under CAP-ACP executive committee sponsorship, a working group was formed to develop a comprehensive guideline for this scenario. To inform the document’s development, the group carried out an extensive literature review, surveyed practices in laboratories across Canada, and reviewed practices in pathology colleges in the United Kingdom, Australasia, and the United States. The Tricouncil Interagency in Research Ethics in Canada, the Canadian Medical Protective Association and members of the CAP-ACP were consulted. Results. Neither the published literature nor the trans-Canadian laboratory survey identified a guideline document. The Royal College of Pathologists of Australasia had a policy and procedure for the scenario; other colleges did not. The guideline developed by the working group listed roles for the ethics committee, researcher, original pathologist, and laboratory in managing the scenario and incorporated the input acquired in the consultation phase. The final document was endorsed in 2012 by the CAP-ACP executive committee and is available on the website (available from: http://www.cap-acp.org/psqa.cfm). Conclusion. The guideline is anchored in principles of patient safety and can be used to minimize and/ or manage changes in the pathologic diagnosis which arise from a research-based review of prior pathology reports. (Surgery 2013;154:111-5.) From the Departments of Pathology and Laboratory Medicine, University of Calgary,a Calgary, Alberta; University of Toronto,b Toronto, Ontario, Canada; the H. Lee Moffitt Cancer Center,c Tampa, FL; and McGill University,d Montreal, Quebec, Canada
CLINICAL AND TRANSLATIONAL RESEARCH involving human subjects may include a review of pathology material belonging to individual patients. The material is usually hematoxylin and eosin-stained glass slides obtained from formalin-fixed, paraffin-embedded blocks of tissue. Research-based pathology reviews are conducted mostly to establish an accurate pathology diagnosis against which associations between the variables or factors (eg, clinical, pathologic, treatment, biomarker expression, genetic
Accepted for publication February 5, 2013. Reprint requests: Maire A. Duggan, MD, FRCPC, Department of Pathology and Laboratory Medicine, Foothills Hospital, Room C1135, 1403 29th Street NW, Calgary, Alberta, Canada T2N 2T9. E-mail: [email protected]. 0039-6060/$ - see front matter Ó 2013 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2013.02.009
profiling) under investigation are measured and correlated with disease outcome. These reviews could change the original diagnosis. Other reviews are done merely for the selection of tissue samples representative of the patients’ original diagnoses and generally do not create a potential for a change in their diagnosis. Research involving humans requires ethical and scientific approval from the appropriate Research Ethics Board, and patient information including their pathology material is coded, namely, anonymized and/or de-identified to maintain patients’ privacy. The major issue stemming from research which includes a pathology review is how to handle any changes to the ‘‘original diagnosis’’ generated by the ‘‘review diagnosis,’’ which may have a potential impact on patient care. Nondisclosure of changes to the ‘‘original diagnosis’’ to the patient or their health care team is a common practice and promoted as a standard of practice by some SURGERY 111
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authors.1,2 Reasons in support of this approach relate to the impracticality or inconsequential and even harmful benefit of communicating changes in diagnoses to those who may be deceased or seriously ill or may not need a different management. Nondisclosure of changes to the ‘‘original diagnosis’’ by the ‘‘review diagnosis,’’ however, is not consistent with current expert opinion on ethical research involving humans. The ethicists, Angelos and Kodner3 and Hebert et al4 advocate for disclosure of any revisions to the ‘‘original diagnosis,’’ and this is also the recommendation of the second edition of the Canadian Tri-Council Policy Statement on ‘‘Ethical Conduct for Research Involving Humans.’’5 Nondisclosure is also inconsistent with transparency and full disclosure principles which have been adopted by health care institutions.6-8 Research-based pathology reviews, however, are of variable intensities and abilities which may limit the accuracy of the ‘‘review diagnosis.’’ Some reviews, for example, may look only at a few representative slides or recut slides from a case, may not control for observer or hindsight bias, and may be performed by individuals without expertise in the disease under study or without appropriate certification in pathology. Diagnostic threshold variability among reviewers can be particularly problematic, as in the diagnosis of follicular variant of thyroid papillary carcinoma, which can generate falsenegative results if the reviewers’ thresholds are less than the original pathologists.9 In other situations, the review may occur so long after the original diagnosis that the criteria for a specific diagnosis may have changed in the interim. To be compliant with a policy of full disclosure, however, processes to ensure any change from the ‘‘original diagnosis’’ by the ‘‘review diagnosis’’ generated in the research context should be scrutinized carefully to confirm the patient’s diagnosis and assess the impact of any change in diagnosis primarily on the patient’s care and secondarily on prognosis.10 The goal of this process sponsored by the Canadian Association of Pathologists-Association Canadienne des Pathologistes (CAP-ACP; www.cap-acp.org) was to create a guideline document anchored in principles of patient safety and disclosure and which would address and encompass changes, modifications, and/or refinements necessary to minimize and/or manage changes in pathology diagnosis which arise from a research-based pathology review. METHODS The volunteer working group was formed in 2010 and reviewed the published literature using the following search terms: Pathology, clinical,
Surgery July 2013
forensic, molecular, surgical, telepathology, bioethical issues, bioethics, ethics, codes of ethics, ethics professional, ethics clinical, ethics medical, ethics committee, research, ethics research, principlebased ethics, disclosure, truth disclosure, diagnostic errors, and referral and consultation. During the months of June and July 2011, the working group surveyed chairs of Canadian university departments of pathology and laboratory medicine and medical directors of laboratories in Canada to gather up-to-date information on the existence of guidelines on the review of pathology in the research context. A total of 219 surveys were sent electronically using Survey Monkey (www.surveymonkey.com) and re-sent once to those who had not responded within 3 weeks. One question was designed to capture general information on the responders’ laboratory practice and 8 questions gathered specific information on policies and practices relating to the issue of researcher requests for pathology materials and the management of changes to diagnosis arising from that request or other review activities, for example, tumor board reviews and retrospective second opinion reviews. All responses were anonymous. The Royal College of Pathologists (www.rcpath. org), the Royal College of Pathologists of Australasia (www.rcpa.edu.au), and the College of American Pathologists (www.cap.org) were surveyed by email and/or mail and asked the same 8 questions. The Tricouncil Interagency in Research Ethics in Canada (www.pre.ethics.gc.ca) and the Canadian Medical Protective Association (CMPA; www. cmpa-acpm.ca) reviewed a draft of the guideline and provided written input. The executive committee and the voting members of the CAP-ACP received a draft for consultation and had a 2-month period in which to provide written feedback. RESULTS Approximately 150 published articles were reviewed. Most of the literature related to laboratory diagnostic error and impact on patient safety. There was a paucity of publications describing and proposing solutions to the specific scenario being addressed by the working group. The CMPA publications ‘‘Learning From Adverse Events: Fostering a Just Culture of Safety in Canadian Hospitals and Health Care Institutions’’11 and the ‘‘Disclosure Booklet’’12 as well as the CAP-ACP ‘‘Interim Guidelines for the Investigation of Alleged Irregularities in Surgical Pathology Practice’’13 were reviewed and informed the preparation of the RPRC guideline.
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Despite our approach, only 21 (10%) surveys were completed. Responders were from 7 provinces and 1 territory. Most responses were from Ontario (38%) or Alberta (19%). Three provinces and 2 territories did not respond. Responders represented public hospitals, and public provincial and private community laboratories. Most responders (38%) were from hospital laboratories serving 200–299 beds; 48% were medical directors of laboratories, and 67% stated they engaged in research which included basic, translational, and clinical work. One third did not participate in any research activity. The vast majority (90%) of responders did not have policy for the question on ‘‘the access and review of pathology materials when a component of the research involved a pathology review and could result in a potential revision of the original pathology diagnosis.’’ Some responders commented that these situations were considered diagnostic discrepancies, and they applied their own in-house policy to those circumstances, whereas others cited ad hoc solutions on a case-by-case basis. The majority of responders (85%) required researchers to provide approval from the appropriate Research Ethics Board before releasing material, particularly documentation of patientinformed consent. Other conditions included a review of the research protocol (45%), consent of the original pathologist to release the materials (25%), review of the material by the original pathologist before release (40%), timelines for the return of the material (45%), ability to retrieve materials immediately from the researcher if needed for patient care (55%), and/or creation/ execution of a Materials Transfer Agreement (15%). When asked what materials they released, 50% released representative materials, 40% released original paraffin blocks, 30% released all original glass slides, and $1 responder released all original glass slides and blocks. When asked if their laboratory had a policy regarding ‘‘reviews of pathology case materials in general (ie, tumor board, second opinion) where this review might result in a change of diagnosis,’’ 55% had a policy. The small number of responses was insufficient to draw statistically valid conclusions. Based on the responses received, however, RPRC guidelines are mostly nonexistent and nearly half of the laboratories do not have policy on the ‘‘reviews of pathology case materials in general (ie, tumor board, second opinion) where this review might result in a change of diagnosis.’’ Because these observations are based mostly on responses received from institutions engaged in research, the
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void provides support for the creation of a RPRC guideline. Written responses were received from all 3 pathology colleges. The Royal College of Pathologists of Australasia and the College of American Pathologists had policies somewhat related to the issues within the scenario. The Royal College of Pathologists did not have a policy specific to the scenario. Section 3.4, entitled ‘‘Review of material requested for purposes of research’’ of the Royal College of Pathologists of Australasia policy on the ‘‘Provision of Second and Subsequent Opinions with Particular Reference to Histopathology, Cytology, and Specimens for Morphological Examination,’’ lists patient consent or waiver by the Research Ethics Board is a requirement. The policy also states material may need to be de-identified, it should only be used for the purposes specified in the original request, and the original material should be returned when the research is complete. This policy goes on to state that in the event a researcher wishes to provide a second and subsequent opinion, the process of section 3.2, labeled ‘‘Second and Subsequent opinions requested by a third party who is a medical practitioner currently involved in the medical care of the patient from whom the pathologic material was originally obtained,’’ must be followed with an approach to the pathologist of record being made before this is done. This section, however, relates only to opinions derived from an institution different from the one to which the material was submitted originally and states arrangements between departments or units within the same institution are for them to be determined internally. The policy of the College of American Pathologists entitled ‘‘Custodianship of Human Biospecimens and Their Derived Products’’ make somewhat similar stipulations with regard to releasing and storing biospecimens, but does not make any stipulation about the management of a changed diagnostic opinion. None of the 3 pathology organizations had a comprehensive policy addressing the review of pathology material in the research context and the management of changes in diagnosis that may arise. The Royal College of Pathologists of Australasia came closest, but the section on second and subsequent opinions did not go far enough, because it did not describe the handling of differences of opinion within the same institution. The similarities between earlier drafts of the CAP-ACP RPRC guideline, which preceded the receipt of copies of policies from the Royal College of Pathologists of Australasia and the College of American Pathologists, were notable. Thus, despite
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jurisdictional and geographic differences, issues around the review of pathology in the research context have international commonality and similarity in the proposed resolution. The Tricouncil and CMPA personal communications to the working group were reviewed and proposed modifications, and changes were included in the final document as were the comments from the executive and membership of the CAP-ACP. The final document was endorsed by the CAP-ACP executive committee May 31, 2012. RPRC GUIDELINE The guideline is anchored in principles of patient safety and describes procedures for the review of pathology in a research context to minimize changes in the ‘‘original diagnosis’’ and manage possible changes to the ‘‘original diagnosis’’ that may arise from the review. It is not expected to replace other appropriate policy and procedure for conducting pathology reviews and addressing possible discrepancies with the ‘‘original diagnosis.’’ The guideline is designed to provide guidance where no policy or procedure exists or is incomplete; it is not intended to define a standard of care. The CAP-ACP does not expect the document to replace clinical judgment, and expects that judgment in individual cases will be made by the physician with appropriate regard to the individual circumstances, including available resources. The CAP-ACP does not warrant that adherence to the guideline will produce a successful outcome in every case. The full guideline is available on the CAP-ACP website (http://www.cap-acp.org/psqa.cfm) and addresses the roles of the Research Ethics Board, the researcher, and the original pathologist and laboratory in 3 tables. Roles and detailed procedures are described for each of the 3 sectors. An integrated list of sectors involved in the scenario is presented to promote coordination between them. Briefly, the role of the Research Ethics Board is to enable full disclosure by releasing the identity of patients whose care may be impacted by a ‘‘review diagnosis,’’ which is different from the ‘‘original diagnosis.’’ To that end, the Research Ethics Board has policy and procedure based on, but not limited to, the Tricouncil policy statement5 on patient disclosure and identification and ensures researchers comply with them. The role of the researcher is to describe how the pathology review will be conducted and how a ‘‘review diagnosis,’’ which is different to the ‘‘original diagnosis’’ will be communicated. This description will be part of the research proposal. It will ensure the reviewers are qualified to
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carry out a pathology review and that measures to ensure the review is unbiased are applied.10 The researcher will communicate any ‘‘review diagnosis’’ that is different from the ‘‘original diagnosis’’ to the Research Ethics Board, the original pathologist, and the medical director of the laboratory who released the material. The lengthiest part of the guideline relates to the original pathologist and laboratory. Their role is to release pathology material to the researchers and when notified that the ‘‘review diagnosis’’ is different to the ‘‘original diagnosis,’’ the original pathologist and the laboratory should take immediate action to ‘‘confirm’’ the patient’s diagnosis, assess the patient safety impact of any confirmed change, and communicate the confirmed change. Many of the procedures listed are not new. They have been recommended practice for some time and are usual operating procedure in many laboratories. Key procedures are as follows. The original pathologist has primary responsibility for further management of the ‘‘review diagnosis’’ that is different from the ‘‘original diagnosis.’’ In the event that the original pathologist is unavailable, the medical director of the laboratory must assume or delegate that role. There is immediate action on the ‘‘review diagnosis’’ change in the ‘‘original diagnosis’’ so that patient care, if needed, is not compromised. Action is guided by the laboratories policy and procedure on changes or revisions to diagnosis, which assesses the discrepancy if any between the ‘‘original and review diagnoses’’ and evaluates the patient care impact in the event of a discrepancy. This approach can be developed based on the CAP-ACP ‘‘Interim Guidelines for the investigation of Alleged Irregularities in Surgical Pathology Practice’’ if none exists or is incomplete and should be conducted whenever possible under the auspices of properly constituted quality assurance committees.14,15 The potential impact on patient care of the change in diagnosis arising from the ‘‘review diagnosis’’ is classified per suggested criteria (eg, no harm, near miss, minimal harm, moderate harm, or severe harm).14 The original pathologist (or medical director/delegate) then takes further action to establish a ‘‘confirmed diagnosis’’ for the patient. If the ‘‘confirmed diagnosis’’ is different from the ‘‘original diagnosis,’’ patient impact is assessed, and the physician of record is informed. An amended pathology report is issued and disclosure to the patient complies with the policy and procedure of the health care institution where the patients care was/is delivered. Although this version of the guideline was developed for Canadian practice, it can easily be
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applied in other jurisdictions. Thus, this guideline serves as a convenient checklist for roles and procedures to be followed when this scenario arises that can be reviewed and acted on. The working group thanks Dr Patricia Shaw, FRCPC, pathologist University Health Network, Toronto, Ontario, for her contributions to the early stages of the guideline development. Ms Rouhi Fazelrad, librarian at the Princess Margaret Hospital, Toronto, Ontario, is thanked for her valuable assistance in conducting the literature search. Dr Finbarr E. Cotter, Royal College of Pathologists, the secretariat of the Royal College of Pathologists of Australasia, Drs Stanley Robboy and Stephen Bauer, College of American Pathologists, Mr John E. Gray, CMPA, and Ms Susan Zimmerman, TriCouncil, are thanked for providing valuable input. REFERENCES 1. Colgan TJ. Disclosure of diagnostic errors: the death knell of retrospective pathology reviews? J Low Genit Tract Disease 2005;9:216-8. 2. Dintzis SM, Gallagher TH. Disclosing harmful pathology errors to patients. Am J Clin Pathol 2009;131:463-5. 3. Angelos P, Kodner I. Changing the diagnosis with retrospective review: a consideration of ethical issues. Surgery 2008; 144:99-100. 4. Hebert PC, Levin AV, Robertson G. Bioethics for clinicians 23: disclosure of medical error. Can Med Assoc J 2001;164:509-13. 5. Tri-Council policy statement: ethical conduct for research involving humans. 2nd edition. Ottawa (Canada): Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada and Social Sciences and Humanities Research Council of Canada [updated 2010 Dec] Available from: www.pre.ethics.gc.ca/pdf/eng/ tcps2/TCPS_2_FINAL_Web.pdf.
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6. Joint Commission on Accreditation of Healthcare Organizations. Hospital accreditation standards, 2007. Oakbrook Terrace (IL): Joint Commission Resources; 2007. 7. The Full Disclosure Working Group. When things go wrong: responding to adverse events: a consensus based statement of the Harvard Hospitals. Boston: Massachusetts Coalition for the Prevention of Medical Errors; 2006. 8. Gallagher TH, Denham C, Leape L, Amori G, Levinson W. Disclosing unanticipated outcomes to patients: the art and the practice. J Patient Saf 2007;3:158-65. 9. Widder S, Guggisberg K, Khalil M, Pasieka JL. A pathologic re-review of follicular thyroid neoplasms: the impact of changing the threshold for the diagnosis of the follicular variant of papillary thyroid carcinoma. Surgery 2008;144:80-5. 10. Duggan MA, Doig CJ. Pathology reviews in the research context: future directions. Surgery 2010;147:887-9. 11. Canadian Medical Protective Association. Learning from adverse events: fostering a just culture of safety in Canadian hospitals and health care institutions. Available from: www. cmpa-acpm.ca/cmpapd04/docs/submissions_papers/pdf/ com_learning_from_adverse_events-e.pdf. 12. Canadian Medical Protective Association. Disclosure booklet. Communicating with your patient about harm. Disclosure of adverse events. Suggestions to help CMPA members meet their patients’ clinical, information and emotional needs after an adverse event. Available from: www. cmpa-acpm.ca/cmpapd04/docs/resource_files/ml_guides/ disclosure/pdf/com_disclosure_toolkit-e.pdf. 13. Duggan MA, DiFrancesco L, Alakija P, Falk V. Letter to the editor re: A pathologic re-review of follicular thyroid neoplasms: the impact of changing the threshold for the diagnosis of the follicular variant of papillary thyroid carcinoma. Surgery 2009;145:687-8. 14. CAP-ACP interim guidelines for the investigation of alleged irregularities in surgical pathology practice. Available from: www.cap-acp.org/guidelines.cfm. 15. Sidhu D, Duggan MA. Statutory and common law protection of laboratory quality assurance data in Canada. Can J Pathol 2012;4:14-8.
Background. Research involving a retrospective review of a patient’s pathology could change the original pathologist’s diagnosis and alter management, treatment, and prognosis. In the interests of patient safety, this review diagnosis needs to be validated and the impact on patient care assessed before disclosure to the patient occurs. The Canadian Association of Pathologists-Association Canadienne des Pathologistes (CAP-ACP) did not have a guideline for managing this scenario. Methods. Under CAP-ACP executive committee sponsorship, a working group was formed to develop a comprehensive guideline for this scenario. To inform the document’s development, the group carried out an extensive literature review, surveyed practices in laboratories across Canada, and reviewed practices in pathology colleges in the United Kingdom, Australasia, and the United States. The Tricouncil Interagency in Research Ethics in Canada, the Canadian Medical Protective Association and members of the CAP-ACP were consulted. Results. Neither the published literature nor the trans-Canadian laboratory survey identified a guideline document. The Royal College of Pathologists of Australasia had a policy and procedure for the scenario; other colleges did not. The guideline developed by the working group listed roles for the ethics committee, researcher, original pathologist, and laboratory in managing the scenario and incorporated the input acquired in the consultation phase. The final document was endorsed in 2012 by the CAP-ACP executive committee and is available on the website (available from: http://www.cap-acp.org/psqa.cfm). Conclusion. The guideline is anchored in principles of patient safety and can be used to minimize and/ or manage changes in the pathologic diagnosis which arise from a research-based review of prior pathology reports. (Surgery 2013;154:111-5.) From the Departments of Pathology and Laboratory Medicine, University of Calgary,a Calgary, Alberta; University of Toronto,b Toronto, Ontario, Canada; the H. Lee Moffitt Cancer Center,c Tampa, FL; and McGill University,d Montreal, Quebec, Canada
CLINICAL AND TRANSLATIONAL RESEARCH involving human subjects may include a review of pathology material belonging to individual patients. The material is usually hematoxylin and eosin-stained glass slides obtained from formalin-fixed, paraffin-embedded blocks of tissue. Research-based pathology reviews are conducted mostly to establish an accurate pathology diagnosis against which associations between the variables or factors (eg, clinical, pathologic, treatment, biomarker expression, genetic
Accepted for publication February 5, 2013. Reprint requests: Maire A. Duggan, MD, FRCPC, Department of Pathology and Laboratory Medicine, Foothills Hospital, Room C1135, 1403 29th Street NW, Calgary, Alberta, Canada T2N 2T9. E-mail: [email protected]. 0039-6060/$ - see front matter Ó 2013 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2013.02.009
profiling) under investigation are measured and correlated with disease outcome. These reviews could change the original diagnosis. Other reviews are done merely for the selection of tissue samples representative of the patients’ original diagnoses and generally do not create a potential for a change in their diagnosis. Research involving humans requires ethical and scientific approval from the appropriate Research Ethics Board, and patient information including their pathology material is coded, namely, anonymized and/or de-identified to maintain patients’ privacy. The major issue stemming from research which includes a pathology review is how to handle any changes to the ‘‘original diagnosis’’ generated by the ‘‘review diagnosis,’’ which may have a potential impact on patient care. Nondisclosure of changes to the ‘‘original diagnosis’’ to the patient or their health care team is a common practice and promoted as a standard of practice by some SURGERY 111
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authors.1,2 Reasons in support of this approach relate to the impracticality or inconsequential and even harmful benefit of communicating changes in diagnoses to those who may be deceased or seriously ill or may not need a different management. Nondisclosure of changes to the ‘‘original diagnosis’’ by the ‘‘review diagnosis,’’ however, is not consistent with current expert opinion on ethical research involving humans. The ethicists, Angelos and Kodner3 and Hebert et al4 advocate for disclosure of any revisions to the ‘‘original diagnosis,’’ and this is also the recommendation of the second edition of the Canadian Tri-Council Policy Statement on ‘‘Ethical Conduct for Research Involving Humans.’’5 Nondisclosure is also inconsistent with transparency and full disclosure principles which have been adopted by health care institutions.6-8 Research-based pathology reviews, however, are of variable intensities and abilities which may limit the accuracy of the ‘‘review diagnosis.’’ Some reviews, for example, may look only at a few representative slides or recut slides from a case, may not control for observer or hindsight bias, and may be performed by individuals without expertise in the disease under study or without appropriate certification in pathology. Diagnostic threshold variability among reviewers can be particularly problematic, as in the diagnosis of follicular variant of thyroid papillary carcinoma, which can generate falsenegative results if the reviewers’ thresholds are less than the original pathologists.9 In other situations, the review may occur so long after the original diagnosis that the criteria for a specific diagnosis may have changed in the interim. To be compliant with a policy of full disclosure, however, processes to ensure any change from the ‘‘original diagnosis’’ by the ‘‘review diagnosis’’ generated in the research context should be scrutinized carefully to confirm the patient’s diagnosis and assess the impact of any change in diagnosis primarily on the patient’s care and secondarily on prognosis.10 The goal of this process sponsored by the Canadian Association of Pathologists-Association Canadienne des Pathologistes (CAP-ACP; www.cap-acp.org) was to create a guideline document anchored in principles of patient safety and disclosure and which would address and encompass changes, modifications, and/or refinements necessary to minimize and/or manage changes in pathology diagnosis which arise from a research-based pathology review. METHODS The volunteer working group was formed in 2010 and reviewed the published literature using the following search terms: Pathology, clinical,
Surgery July 2013
forensic, molecular, surgical, telepathology, bioethical issues, bioethics, ethics, codes of ethics, ethics professional, ethics clinical, ethics medical, ethics committee, research, ethics research, principlebased ethics, disclosure, truth disclosure, diagnostic errors, and referral and consultation. During the months of June and July 2011, the working group surveyed chairs of Canadian university departments of pathology and laboratory medicine and medical directors of laboratories in Canada to gather up-to-date information on the existence of guidelines on the review of pathology in the research context. A total of 219 surveys were sent electronically using Survey Monkey (www.surveymonkey.com) and re-sent once to those who had not responded within 3 weeks. One question was designed to capture general information on the responders’ laboratory practice and 8 questions gathered specific information on policies and practices relating to the issue of researcher requests for pathology materials and the management of changes to diagnosis arising from that request or other review activities, for example, tumor board reviews and retrospective second opinion reviews. All responses were anonymous. The Royal College of Pathologists (www.rcpath. org), the Royal College of Pathologists of Australasia (www.rcpa.edu.au), and the College of American Pathologists (www.cap.org) were surveyed by email and/or mail and asked the same 8 questions. The Tricouncil Interagency in Research Ethics in Canada (www.pre.ethics.gc.ca) and the Canadian Medical Protective Association (CMPA; www. cmpa-acpm.ca) reviewed a draft of the guideline and provided written input. The executive committee and the voting members of the CAP-ACP received a draft for consultation and had a 2-month period in which to provide written feedback. RESULTS Approximately 150 published articles were reviewed. Most of the literature related to laboratory diagnostic error and impact on patient safety. There was a paucity of publications describing and proposing solutions to the specific scenario being addressed by the working group. The CMPA publications ‘‘Learning From Adverse Events: Fostering a Just Culture of Safety in Canadian Hospitals and Health Care Institutions’’11 and the ‘‘Disclosure Booklet’’12 as well as the CAP-ACP ‘‘Interim Guidelines for the Investigation of Alleged Irregularities in Surgical Pathology Practice’’13 were reviewed and informed the preparation of the RPRC guideline.
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Despite our approach, only 21 (10%) surveys were completed. Responders were from 7 provinces and 1 territory. Most responses were from Ontario (38%) or Alberta (19%). Three provinces and 2 territories did not respond. Responders represented public hospitals, and public provincial and private community laboratories. Most responders (38%) were from hospital laboratories serving 200–299 beds; 48% were medical directors of laboratories, and 67% stated they engaged in research which included basic, translational, and clinical work. One third did not participate in any research activity. The vast majority (90%) of responders did not have policy for the question on ‘‘the access and review of pathology materials when a component of the research involved a pathology review and could result in a potential revision of the original pathology diagnosis.’’ Some responders commented that these situations were considered diagnostic discrepancies, and they applied their own in-house policy to those circumstances, whereas others cited ad hoc solutions on a case-by-case basis. The majority of responders (85%) required researchers to provide approval from the appropriate Research Ethics Board before releasing material, particularly documentation of patientinformed consent. Other conditions included a review of the research protocol (45%), consent of the original pathologist to release the materials (25%), review of the material by the original pathologist before release (40%), timelines for the return of the material (45%), ability to retrieve materials immediately from the researcher if needed for patient care (55%), and/or creation/ execution of a Materials Transfer Agreement (15%). When asked what materials they released, 50% released representative materials, 40% released original paraffin blocks, 30% released all original glass slides, and $1 responder released all original glass slides and blocks. When asked if their laboratory had a policy regarding ‘‘reviews of pathology case materials in general (ie, tumor board, second opinion) where this review might result in a change of diagnosis,’’ 55% had a policy. The small number of responses was insufficient to draw statistically valid conclusions. Based on the responses received, however, RPRC guidelines are mostly nonexistent and nearly half of the laboratories do not have policy on the ‘‘reviews of pathology case materials in general (ie, tumor board, second opinion) where this review might result in a change of diagnosis.’’ Because these observations are based mostly on responses received from institutions engaged in research, the
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void provides support for the creation of a RPRC guideline. Written responses were received from all 3 pathology colleges. The Royal College of Pathologists of Australasia and the College of American Pathologists had policies somewhat related to the issues within the scenario. The Royal College of Pathologists did not have a policy specific to the scenario. Section 3.4, entitled ‘‘Review of material requested for purposes of research’’ of the Royal College of Pathologists of Australasia policy on the ‘‘Provision of Second and Subsequent Opinions with Particular Reference to Histopathology, Cytology, and Specimens for Morphological Examination,’’ lists patient consent or waiver by the Research Ethics Board is a requirement. The policy also states material may need to be de-identified, it should only be used for the purposes specified in the original request, and the original material should be returned when the research is complete. This policy goes on to state that in the event a researcher wishes to provide a second and subsequent opinion, the process of section 3.2, labeled ‘‘Second and Subsequent opinions requested by a third party who is a medical practitioner currently involved in the medical care of the patient from whom the pathologic material was originally obtained,’’ must be followed with an approach to the pathologist of record being made before this is done. This section, however, relates only to opinions derived from an institution different from the one to which the material was submitted originally and states arrangements between departments or units within the same institution are for them to be determined internally. The policy of the College of American Pathologists entitled ‘‘Custodianship of Human Biospecimens and Their Derived Products’’ make somewhat similar stipulations with regard to releasing and storing biospecimens, but does not make any stipulation about the management of a changed diagnostic opinion. None of the 3 pathology organizations had a comprehensive policy addressing the review of pathology material in the research context and the management of changes in diagnosis that may arise. The Royal College of Pathologists of Australasia came closest, but the section on second and subsequent opinions did not go far enough, because it did not describe the handling of differences of opinion within the same institution. The similarities between earlier drafts of the CAP-ACP RPRC guideline, which preceded the receipt of copies of policies from the Royal College of Pathologists of Australasia and the College of American Pathologists, were notable. Thus, despite
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jurisdictional and geographic differences, issues around the review of pathology in the research context have international commonality and similarity in the proposed resolution. The Tricouncil and CMPA personal communications to the working group were reviewed and proposed modifications, and changes were included in the final document as were the comments from the executive and membership of the CAP-ACP. The final document was endorsed by the CAP-ACP executive committee May 31, 2012. RPRC GUIDELINE The guideline is anchored in principles of patient safety and describes procedures for the review of pathology in a research context to minimize changes in the ‘‘original diagnosis’’ and manage possible changes to the ‘‘original diagnosis’’ that may arise from the review. It is not expected to replace other appropriate policy and procedure for conducting pathology reviews and addressing possible discrepancies with the ‘‘original diagnosis.’’ The guideline is designed to provide guidance where no policy or procedure exists or is incomplete; it is not intended to define a standard of care. The CAP-ACP does not expect the document to replace clinical judgment, and expects that judgment in individual cases will be made by the physician with appropriate regard to the individual circumstances, including available resources. The CAP-ACP does not warrant that adherence to the guideline will produce a successful outcome in every case. The full guideline is available on the CAP-ACP website (http://www.cap-acp.org/psqa.cfm) and addresses the roles of the Research Ethics Board, the researcher, and the original pathologist and laboratory in 3 tables. Roles and detailed procedures are described for each of the 3 sectors. An integrated list of sectors involved in the scenario is presented to promote coordination between them. Briefly, the role of the Research Ethics Board is to enable full disclosure by releasing the identity of patients whose care may be impacted by a ‘‘review diagnosis,’’ which is different from the ‘‘original diagnosis.’’ To that end, the Research Ethics Board has policy and procedure based on, but not limited to, the Tricouncil policy statement5 on patient disclosure and identification and ensures researchers comply with them. The role of the researcher is to describe how the pathology review will be conducted and how a ‘‘review diagnosis,’’ which is different to the ‘‘original diagnosis’’ will be communicated. This description will be part of the research proposal. It will ensure the reviewers are qualified to
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carry out a pathology review and that measures to ensure the review is unbiased are applied.10 The researcher will communicate any ‘‘review diagnosis’’ that is different from the ‘‘original diagnosis’’ to the Research Ethics Board, the original pathologist, and the medical director of the laboratory who released the material. The lengthiest part of the guideline relates to the original pathologist and laboratory. Their role is to release pathology material to the researchers and when notified that the ‘‘review diagnosis’’ is different to the ‘‘original diagnosis,’’ the original pathologist and the laboratory should take immediate action to ‘‘confirm’’ the patient’s diagnosis, assess the patient safety impact of any confirmed change, and communicate the confirmed change. Many of the procedures listed are not new. They have been recommended practice for some time and are usual operating procedure in many laboratories. Key procedures are as follows. The original pathologist has primary responsibility for further management of the ‘‘review diagnosis’’ that is different from the ‘‘original diagnosis.’’ In the event that the original pathologist is unavailable, the medical director of the laboratory must assume or delegate that role. There is immediate action on the ‘‘review diagnosis’’ change in the ‘‘original diagnosis’’ so that patient care, if needed, is not compromised. Action is guided by the laboratories policy and procedure on changes or revisions to diagnosis, which assesses the discrepancy if any between the ‘‘original and review diagnoses’’ and evaluates the patient care impact in the event of a discrepancy. This approach can be developed based on the CAP-ACP ‘‘Interim Guidelines for the investigation of Alleged Irregularities in Surgical Pathology Practice’’ if none exists or is incomplete and should be conducted whenever possible under the auspices of properly constituted quality assurance committees.14,15 The potential impact on patient care of the change in diagnosis arising from the ‘‘review diagnosis’’ is classified per suggested criteria (eg, no harm, near miss, minimal harm, moderate harm, or severe harm).14 The original pathologist (or medical director/delegate) then takes further action to establish a ‘‘confirmed diagnosis’’ for the patient. If the ‘‘confirmed diagnosis’’ is different from the ‘‘original diagnosis,’’ patient impact is assessed, and the physician of record is informed. An amended pathology report is issued and disclosure to the patient complies with the policy and procedure of the health care institution where the patients care was/is delivered. Although this version of the guideline was developed for Canadian practice, it can easily be
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applied in other jurisdictions. Thus, this guideline serves as a convenient checklist for roles and procedures to be followed when this scenario arises that can be reviewed and acted on. The working group thanks Dr Patricia Shaw, FRCPC, pathologist University Health Network, Toronto, Ontario, for her contributions to the early stages of the guideline development. Ms Rouhi Fazelrad, librarian at the Princess Margaret Hospital, Toronto, Ontario, is thanked for her valuable assistance in conducting the literature search. Dr Finbarr E. Cotter, Royal College of Pathologists, the secretariat of the Royal College of Pathologists of Australasia, Drs Stanley Robboy and Stephen Bauer, College of American Pathologists, Mr John E. Gray, CMPA, and Ms Susan Zimmerman, TriCouncil, are thanked for providing valuable input. REFERENCES 1. Colgan TJ. Disclosure of diagnostic errors: the death knell of retrospective pathology reviews? J Low Genit Tract Disease 2005;9:216-8. 2. Dintzis SM, Gallagher TH. Disclosing harmful pathology errors to patients. Am J Clin Pathol 2009;131:463-5. 3. Angelos P, Kodner I. Changing the diagnosis with retrospective review: a consideration of ethical issues. Surgery 2008; 144:99-100. 4. Hebert PC, Levin AV, Robertson G. Bioethics for clinicians 23: disclosure of medical error. Can Med Assoc J 2001;164:509-13. 5. Tri-Council policy statement: ethical conduct for research involving humans. 2nd edition. Ottawa (Canada): Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada and Social Sciences and Humanities Research Council of Canada [updated 2010 Dec] Available from: www.pre.ethics.gc.ca/pdf/eng/ tcps2/TCPS_2_FINAL_Web.pdf.
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6. Joint Commission on Accreditation of Healthcare Organizations. Hospital accreditation standards, 2007. Oakbrook Terrace (IL): Joint Commission Resources; 2007. 7. The Full Disclosure Working Group. When things go wrong: responding to adverse events: a consensus based statement of the Harvard Hospitals. Boston: Massachusetts Coalition for the Prevention of Medical Errors; 2006. 8. Gallagher TH, Denham C, Leape L, Amori G, Levinson W. Disclosing unanticipated outcomes to patients: the art and the practice. J Patient Saf 2007;3:158-65. 9. Widder S, Guggisberg K, Khalil M, Pasieka JL. A pathologic re-review of follicular thyroid neoplasms: the impact of changing the threshold for the diagnosis of the follicular variant of papillary thyroid carcinoma. Surgery 2008;144:80-5. 10. Duggan MA, Doig CJ. Pathology reviews in the research context: future directions. Surgery 2010;147:887-9. 11. Canadian Medical Protective Association. Learning from adverse events: fostering a just culture of safety in Canadian hospitals and health care institutions. Available from: www. cmpa-acpm.ca/cmpapd04/docs/submissions_papers/pdf/ com_learning_from_adverse_events-e.pdf. 12. Canadian Medical Protective Association. Disclosure booklet. Communicating with your patient about harm. Disclosure of adverse events. Suggestions to help CMPA members meet their patients’ clinical, information and emotional needs after an adverse event. Available from: www. cmpa-acpm.ca/cmpapd04/docs/resource_files/ml_guides/ disclosure/pdf/com_disclosure_toolkit-e.pdf. 13. Duggan MA, DiFrancesco L, Alakija P, Falk V. Letter to the editor re: A pathologic re-review of follicular thyroid neoplasms: the impact of changing the threshold for the diagnosis of the follicular variant of papillary thyroid carcinoma. Surgery 2009;145:687-8. 14. CAP-ACP interim guidelines for the investigation of alleged irregularities in surgical pathology practice. Available from: www.cap-acp.org/guidelines.cfm. 15. Sidhu D, Duggan MA. Statutory and common law protection of laboratory quality assurance data in Canada. Can J Pathol 2012;4:14-8.