Crippling Clinical Research?

(Disclaimer: This response was written in Dr. Jaffe’s private capacity; the views expressed do not reflect the opinion of official policy of the U.S. government).

I commend Dr. Sekeres for his excellent editorial (Take My Leftover Tissue, Please!), which appeared in the December 2015 issue of ASH Clinical News. The proposed changes to the Common Rule (Docket ID number HHS-OPHS-2015-0008) would cripple research in the pathology research community.

I have been a practicing pathologist doing clinical research for more than 40 years, and I have published nearly 600 articles. I am among the 400 most highly cited researchers in all biomedical sciences between 1996 and 2011.1 The number of citations is evidence of the significance and value of my work. However, you could toss out 90 percent of the articles in my CV, if the proposed restrictions were imposed for studies done on biological specimens considered “excess tissue.”

Most of my published work has been based on novel observations made in the course of diagnostic work, with supplemental studies done on “excess tissue” – sometimes many years after the diagnosis was initially made to better understand and characterize the pathological process. My research has been conducted under an authorized Institutional Review Board–approved protocol, which allows studies of low risk to be performed on biospecimens/pathology tissues without patient consent. Most pathologists do not have direct contact with patients, and obtaining consent for studies to be performed on retrospective specimens is not feasible. (Cited below are representative articles published in Blood that were based on cases submitted to me in consultation.2-7)

When one undertakes a retrospective review of tissue biopsies performed years earlier, the location of the patient or his or her current physician is often unknown. Blocking these research efforts would halt the discovery of new disease entities, discoveries that impact patients’ lives and lead to changes in therapy and management. These studies have led to new insights regarding diagnosis and classification of disease that are reflected in the World Health Organization classification of lymphomas.8

My work is representative of much clinical research conducted by pathologists. Additionally, producing repositories of de-linked or anonymized specimens would not be a solution, even if such specimens were exempted from the rule. If one removes patient identifiers, that specimen is no longer available for clinical review, should it be relevant to the patient’s care. Thus, the de-linking causes potential harm to the patient. Furthermore, it limits such studies to only large surgical resections, which are a rarity in hematologic disease. Additionally, the clinical correlates that are critical to clinical research become much more difficult to obtain. For these reasons, I urge revisions to the proposed Common Rule to allow continued use of “excess tissue” for studies of low risk.


References

  1. Boyack KW, Klavans R, Sorensen AA, et al. A list of highly influential biomedical researchers, 1996–2011. Eur J Clin Invest. 2013;43:1339-65.
  2. Cong P, Raffeld M, Teruya-Feldstein J, et al. In situ localization of follicular lymphoma: description and analysis by laser capture microdissection. Blood. 2002;99:3376-82.
  3. Jegalian AG, Eberle FC, Pack SD, et al. Follicular lymphoma in situ: clinical implications and comparisons with partial involvement by follicular lymphoma. Blood. 2011;118:2976-84.
  4. Feldman AL, Arber DA, Pittaluga S, et al. Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone. Blood. 2008;111:5433-39.
  5. Mansoor A, Pittaluga S, Beck PL, et al. NK-cell enteropathy: a benign NK-cell lymphoproliferative disease mimicking intestinal lymphoma: clinicopathologic features and follow-up in a unique case series. Blood. 2011;117:1447-52.
  6. Perry AM, Warnke RA, Hu Q, et al. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract. Blood. 2013;122:3599-3606.
  7. Nicolae A, Pittaluga S, Abdullah S, et al. EBV-positive large B-cell lymphomas in young patients: a nodal lymphoma with evidence for a tolerogenic immune environment. Blood. 2015;126:863-72.
  8. Campo E, Swerdlow SH, Harris NL, et al. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117:5019-32.

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