Advisor 469

CLINICAL RESEARCH • CLINICAL QUALITY ASSURANCE

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GCP lessons MHRA reports critical data integrity finding during investigator site inspection GCP inspections of investigator sites performed by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) from 1 April 2017 to 31 March 2018 revealed a single critical finding. As described in the MHRA’s annual metrics report for the 12-month period, a total of 17 investigator sites were inspected and the emphasis of each inspection was on how the investigator site had been overseen by the sponsor/ contract research organisation. Across the 17 inspections, one (5.9%) had a critical finding and 11 (64.7%) had at least one major finding. The total number of findings and the number of findings per inspection are summarised in Table 1. will also be useful in other regions, where they should be considered alongside relevant local national or regional regulatory requirements and legislation, including • the European Medicines Agency’s (EMA’s) ‘Guidance on the Management of Clinical Trials Table 1 . Investigator site inspection findings (1 April 2017 to 31 March 2018). Guidance The CTTI document repeatedly references additional information in the applicable FDA guidance and is focused on the USA. However, the recommendations

during the COVID-19 (coronavirus) Pandemic’ (Version 3, 28 April 2020) • the Medicines and Healthcare products Regulatory Agency (MHRA) guidance on manging clinical trials during coronavirus.

Source: ; the FDA guidance is available at , the EMA guidance at and the MHRA guidance at .

Overview Overall, the inspection findings for investigator sites fell into 14 of the 42 listed categories, compared with 24 in the previous 12 months. Major inspection findings were in seven of the 42 different categories. The only category with more than one major finding was case report forms/ source data (with eight findings); the other six findings were all in different categories: data integrity, investigational medicinal product management/pharmacy, medical oversight by the principal investigator, pharmacovigilance, protocol compliance, and staff delegation and responsibility. Critical finding There was one critical inspection finding identified during an investigator site inspection undertaken as an associated site for a commercial sponsor organisation. The finding related to data integrity. The visual analogue scale (VAS) scores used as part of the exploratory endpoint for the trial could not be reconstructed. The scores were supposed to be generated by the patient using a tablet device after they had logged in, with a paper back-up available if the device was not functioning. In most cases both the paper document and the device had been populated, and there were significant differences between the scores. For example, in one case • there was no documentation to explain why there were three different scores for the same data point or which was the true source • time was not recorded on the paper form, which meant that it was not possible to determine which entry was generated first • the score was entered as 36 on the device but written as 60 on the paper document, and when measured was 62 • most of the paper sheets had not been signed by the patient but 80% had been signed by the investigator, so it was not possible to verify who had completed them • of the 60 examples checked by the inspectors, one match was found between the device and paper entries where the patient had entered 100 (maximum) on both.

Type of finding

Number of inspection findings

Mean number of findings/ inspection

Maximum number of inspection findings

Critical Major Other

1

0.1 0.8 3.8 4.7

1 3 6

14 65 80

Total

Not applicable

Compared with the previous 12-month period, there were fewer inspections (17 versus 24) and a small increase in the percentage of sites with critical or major inspection findings. However, for both major and other inspection findings, there was a decrease in the total number of inspection findings, the mean number of inspection findings per inspection and the maximum number of inspection findings compared with the previous 12 months,

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Issue 469, 2020

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