Recommendations for cellular and molecular pathology input into clinical trials: a systematic review and meta‐aggregation

Abstract

The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement was developed to provide guidance for inclusion of key methodological components in clinical trial protocols. However, these standards do not include guidance specific to pathology input in clinical trials. This systematic review aims to synthesise existing recommendations specific to pathology practice in clinical trials for implementation in trial protocol design. Articles were identified from database searches and deemed eligible for inclusion if they contained: (1) guidance and/or a checklist, which was (2) pathology-related, with (3) content relevant to clinical trial protocols or could influence a clinical trial protocol design from a pathology perspective and (4) were published in 1996 or later. The quality of individual papers was assessed using the AGREE-GRS (Appraisal of Guidelines for REsearch & Evaluation -Global Rating Scale) tool, and the confidence in cumulative evidence was evaluated using the GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in Evidence from Reviews of Qualitative research) approach. Extracted recommendations were synthesised using the best fit framework method, which includes thematic analysis followed by a meta-aggregative approach to synthesis within the framework. Of the 10 184 records screened and 199 full-text articles reviewed, only 40 guidance resources met the eligibility criteria for inclusion. Recommendations extracted from 22 guidance documents were generalisable enough for data synthesis. Seven recommendation statements were synthesised as follows: (1) multidisciplinary collaboration in trial design with early involvement of pathologists, particularly with respect to the use of biospecimens and associated biomarker/analytical assays and in the evaluation of pathology-related parameters; (2) funding and training for personnel undertaking trial work; (3) selection of an accredited laboratory with suitable facilities to undertake scheduled work; (4) quality assurance of pathology-related parameters; (5) transparent reporting of pathology-related parameters; (6) policies regarding informatics and tracking biospecimens across trial sites; and (7) informed consent for specimen collection and retention for future research.

Assessment of clinical trial protocols for pathology content using the SPIRIT‐Path guidelines highlights areas for improvement

“…The pilot was used to train and calibrate the assessors and to refine the search strategy. The final search strategy included the search criteria from the ‘pathology‐specific terms’ employed in the systematic review of cellular and molecular pathology input into clinical trials [ 3 ]. Additional search terms were used to identify individual SPIRIT‐Path extensions and elaborations (Table 1 ).…”

“…The National Cancer Research Institute (NCRI) Pathology Group, formerly the Cellular Molecular Pathology Initiative (CMPath), through a project called SPIRIT‐Path, developed an extension to the original SPIRIT statement describing how to effectively incorporate pathology support into clinical trial protocols. A systematic review of existing guidance for pathology items in clinical trials [ 3 ] was used to conduct an international Delphi process from which the SPIRIT‐Path guidelines were derived [ 4 ]. The checklist includes 14 items, seven elaborations and seven extensions, to the SPIRIT 2013 Statement that should be addressed in trial protocols with pathology elements.…”

Promoting Best Practice in Cancer Care in Sub Saharan Africa

“…“There is increasing recognition of the need for pathologists to be involved early in trial planning and design to ensure methodological rigor in trials requiring sample collection, procurement, storage, transportation and analysis” ( 42 ). The recommendations for Interventional Trials 2013 Statement has recently been expanded to include Pathology (SPIRIT-Path) ( 43 ).…”

Digital Pathology Transformation in a Supraregional Germ Cell Tumour Network

“…Digital pathology (DP), whereby whole slide images are created from glass slides (GS) to be viewed on computer workstations for purposes such as primary diagnosis, is now gaining significant traction in clinical practice, particularly in the United Kingdom (UK). Although a small number of laboratories have published their journey to large-scale or full digitization [ 1 , 2 ] and there are a few reports of the use of DP in multi-centre networks [ 3 , 4 ], there is surprisingly very little in the literature on the use of DP for highly specialist services requiring central review—despite the described clinical benefits of such a review [ 5 ] and the already common usage of DP for similar purposes in clinical trials for quality assurance [ 6 ].…”