GenomOncology's Workflow for Curating Institution-Specific Clinical Trial Protocols for Exclusive Use

Clinical trials are governed by extensive, lengthy protocols that can be hundreds of pages long. These documents describe the scientific reasoning for undertaking the trial, identify the patients whom the trial wishes to aid, detail the chemical properties of the investigational drugs, and establish the parameters by which the study will measure the investigational drug’s efficacy. Administrators of clinical trials are responsible for uploading summaries of the trial to ClinicalTrials.gov, the federal database of all trials in the United States. A nightly software job imports all cancer-focused clinical trials on ClinicalTrials.gov to GO Curate, GenomOncology’s internal curation tool.

The curation of a clinical trial by the curators of GenomOncology’s Content Team entails generating a cohort by linking an eligibility with a treatment. A patient can then match to this cohort using GenomOncology’s proprietary match software. An eligibility is composed of cancers (e.g., non-small-cell lung carcinoma), biomarkers (e.g., ALK fusion), and disease states (e.g., metastatic). A treatment contains drugs (e.g., lorlatinib) and treatment settings (e.g., subsequent line). All this information can be present in a clinical trial document from ClinicalTrials.gov.

The key word in the prior sentence, however, is can. The clinical trial’s administrators are not obligated to reveal all the information I described. Some administrators do, but others reveal only the barest of details. This mysteriousness is especially seen in phase-I clinical trials, which often test a novel drug that the manufacturer wishes to conceal from potential competitors. (More information about this novel drug is usually revealed when a patient enrolls on the trial, though.) My fellow curators and I can do little to overcome this dilemma, so we must curate as accurately as possible with the information given on ClinicalTrials.gov. I am confident that patients will accurately match to an applicable trial because of the many fail-safes of the match process. Nevertheless, a trial’s vagueness means some patients could not be matching to a relevant trial available at a client’s location because we lack the information from ClinicalTrials.gov.

Recently, a solution to this problem arose for the GenomOncology Content Team. A partner institution agreed to grant GenomOncology access to its internal database of clinical trial protocols. The Content Team calls these private protocols. In return for being given this access, the Content Team curates the private protocols—not the public protocols from ClinicalTrials.gov—for exclusive use by this institution. So instead of curating the vague information from ClinicalTrials.gov, the comprehensive source material in the private protocol is curated.

As I mentioned earlier, clinical trial protocols are massive documents; rarely do they have fewer than one hundred pages. There is some common structure to the layout of these private protocols. Ultimately, finding the data worthy of curation lies within the purview of the curators of GenomOncology’s Content Team. Curators are already extensively trained in the art of curating public protocols. Curating private protocols allows curators to draw on their past scientific training and critical thinking. The Content Team is able to accurately and efficiently curate private protocols by harmonizing its well-developed internal protocols with its curators’ past experiences.

The first step is to assess whether or not private curation is necessary. The curator who does this is called the assessor. If the curation of a private protocol is identical to the curation of the public protocol from ClinicalTrials.gov, then no private curation is necessary; the client simply matches to the same cohorts to which all of GenomOncology’s other clients can match. If the private protocol would have a different curation than the current public curation (for example, more specific biomarkers are required by the private protocol), then the assessor indicates the trial needs to be privately curated by noting the differences.

If a private protocol needs to be privately curated, a different curator than the one who assessed the trial is assigned. The thinking here is that a different pair of eyes could notice additional changes than an assessor who spent lengthy time embedded in the private protocol’s text. The private curator curates the trial according to the Content Team’s lengthy, comprehensive SOP for trial curation. When finished, the private curator notes the private curation is ready to be reviewed.

The third and final step in private curation is review. A third curator—who was neither the assessor nor the private curator—is assigned to be the reviewer. Reviewers essentially re-curate trials in their heads, ensuring that the private curation can pass muster. Once any problems have been resolved, the reviewer publishes the trial to the client’s private server. Due to the sensitive nature of the information, the privately curated protocol remains entirely on the client's specific installation of the GO Precision Oncology Platform, and does not get added to the centralized database of trials available for all GO clients. GenomOncology’s match software then overrules the existing public curation, so that only the client’s patients can match to the private curation. 

In our most recent assessment, commonly observed differences between public and private protocols were more specific cancers (for example, colorectal carcinoma vs. rectal adenocarcinoma) and biomarkers (for example, any EGFR mutation vs. EGFR L858R). GenomOncology’s Content Team prides itself on enabling the most accurate match to all eligible patients, and curating private protocols furthers our ability to meet this goal. If your institution is interested in the curation of your private protocols, please schedule a demo.