Audit - DOs and DON’Ts - Navigating the World of Clinical Research Audits

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As I am currently preparing for yet another audit myself, I have decided to share with you what I think is a useful audit guide. In this article I have summed up some general guidance and tips and tricks, in case you are to experience your first (or second, or third) audit.

You all already know how my firs-ever went (dreadfully) so I won’t get into details (you could read the full article here). So, let’s dive in.

Audits are an essential part of quality management. Also, I believe that working with external auditors ensures you avoid conflicts of interest and provide an independent perspective.

Why do so many companies panic when a major audit is due? In many cases, the root cause is their continual underinvestment in quality, or even negligence in some cases. This results in staff having to rush around to patch things up before the auditor arrives.

This "sticking plaster" approach is counterproductive because it risks exposing the company's lack of quality monitoring. Instead, companies should embrace providing a high-quality service, because essentially, monitoring is what we do, and data quality and integrity are the products we bring to the table. We should aim for perfection at all times rather than only chasing it a week prior to the audit.

So, how can you prepare yourself and your site to interact with the auditor? Let's take a look!

DON'T - Overshare information

I feel like this should be a no-brainer, but common sense isn't always that common. With that being said, it's very common for the CRA (or the investigator - be sure to prepare your site well) to try to be as open and transparent as possible, and to help the auditor see what a great job the site has done. However, this often leads to oversharing information that no one asked for. This is dangerous as you may reveal something that you should not have said (e.g. unnecessary details, which could come back to bite you) or simply annoy the auditor and give them more possibilities to find something that they otherwise would not have focused on. So, keep your details to yourself unless specifically asked for. Being talkative is never a good strategy during an audit.

DO - Prepare the Auditor

Being audited can be a stressful experience. However, you can ensure as-smooth-as-possible audit by properly preparing and planning for it. Have you ever taken an exam at the university when you didn't know anything, but for some reason, you still decided to give it a try? Now you are sweating in front of your professor because you don't know the answers and he sees the desperation in your eyes? Trust me, you do not want to be in this situation with the auditor - preparation is the key.

The auditor should be informed about what to expect during each interview with the site personnel, what needs to be reviewed with the coordinator, what topics should be covered, and the audit scope. Ideally, preparation should begin several weeks, even a month prior to the actual audit.

DON'T - Flood the Auditor with Documents

Provide the auditor with all the records, documentation, and any additional information they may request. Ideally, the auditor will not be allocated in the same room as the study folders and will ask you to bring him/her whatever is needed. However, avoid overwhelming the auditor with documentation that is not relevant to the audit process. Only provide the materials that will help the auditor better understand the site’s processes and the specific documents that are being requested.

DO - Ask for an Audit Plan Early

An audit plan helps both the auditee and the auditor to map out the audit effectively. It defines the audit work that will be completed and encompasses the overall strategy and detailed approach of the audit’s nature, timing, and scope.

Audit plans should be issued two weeks or so before the audit occurs to know the focus areas under review.

Moreover, your site team must be familiar with the audit plan to the point that they can clearly explain who is responsible for each task and understand the audit agenda step by step.

DON'T - Accept General Templates

If an audit plan can be used for multiple studies, then the auditor probably did not prepare using the pre-audit documents. Therefore, make sure that the template presented is customized to suit your operations.

General templates that do not reflect your site's (CRO) specific quality management system and processes will not add value to the audit process. A generalized template may also slow down an audit due to duplication and repetition. An ideal audit plan must demonstrate a good knowledge of your site processes and company SOPs.

DO - Stay with the Auditor

The CRA should accompany the auditor throughout the entire audit process (yes, even in the bathroom, if necessary). Active involvement is crucial at each stage of the audit to identify issues or areas of particular concern that should be addressed. Staying with the auditor also facilitates clarification of issues and asking of relevant questions. And God forbid, you leave your study documents unattended in the presence of the auditor. As a monitor, you should not in any circumstances, leave your auditor alone and wandering around.

DON'T - Wait to Ask Questions

Even if the auditor mentions a "wrap up" at the end of the day, don't wait until then to ask questions about their observations. Asking relevant questions lets you seek immediate clarification on areas that are not well understood or covered. This ensures that no issues remain unresolved and that there are no surprises at the conclusion of the audit. Asking questions may also resolve the majority of minor or even some major findings at the end of the day. So, do not be afraid to communicate, this may make the difference between a major or a minor finding.

DO - Take Notes!

During the audit process, take notes alongside the auditor on everything they do. This includes what has been reviewed, where they clicked in the EDC, and how many times they went back to check something for a patient. These notes may help determine if all audit objectives were met and if findings are substantiated. Additionally, CRA notes may cover something that the auditor missed during the closing meeting. They can also be used to argue against an unreasonable finding, if necessary. So, pay attention 😉.

DON'T - Dictate Notes

It should go without saying, but never dictate to the auditor what to write in their notes (please 🙏). Auditors should be free to write what they want and how they want. Dictating notes to the auditor is equivalent to influencing the outcome of the audit, which defeats the entire purpose of using an independent auditor.

DO - Challenge Invalid Non-conformity observations.

An audit seeks to verify that the practices being used conform to what is intended. However, there may be instances where the auditor makes invalid non-conformity observations. If you have reason to believe there is an invalid non-conformity, mention it. If the non-conformity is not a requirement, ask the auditor to make it a recommendation rather than noting a non-conformity.

Failure to challenge invalid non-conformities may result in difficulty identifying root causes and may result in inefficient allocation of resources.

DON'T - Confuse "Experience" with "Requirements"

Auditors may refer to "best practices" or "benchmark" approaches seen at other companies or sites. However, this does not always justify a non-conformity. For example, an auditor might ask to see notifications submitted to the Local Ethics Committee (LEC) because they saw these notifications in previous audits at other sites. However, if this is not a requirement of the regulations, as is the case for the LEC in Bulgaria, it should not be recorded as a non-conformity.

DO - Disseminate Audit Conclusions throughout the Company

Every department manager should receive a copy of the audit report. This ensures that decision-makers have a clear picture of how the CRO/site is operating. An auditor's report points out inefficiencies and weaknesses in monitoring that may need to be addressed similarly in other parts of the company.

To ensure that the trials are conducted in full compliance, work with the your study lead/manager manager to create a CAPA for each nonconformity pointed out by the auditor. This will help to track corrective actions to completion.

Another awesome practice that I appreciate being done at @PSI is the sharing of audit results and unusual findings among colleagues. We even hold regular discussions dedicated to discussing audit findings and how to improve our processes.

DON'T - Accept a "Perfect Score"

Sometimes audits that result in no observations, recommendations, or non-conformities to report but this should not be interpreted as having a perfect system - an audit is just a collection of samples. Rotating auditors is a good way to challenge (very gently) the quality management system with new perspectives. Every auditor looks at things differently. A thorough audit process always points out areas that need improvements. It also provides essential recommendations on the way forward.

* That of course, if you a confident as heel, your audit went well. Otherwise, I definitely would not recommend getting too cocky.

A few more points came up in discussions with colleagues:

In Bulgaria, a CRA shared that during an inspection by IAL (Bulgarian Drug Agency), the auditor took the site identification log and started calling patients to ask if they remembered participating in a clinical trial or when their last visit was. This is usually not a concern, but do keep in mind - we all know at least one site, which has more than 200 enrolled patients with a rare study indication in a remote area of the unknown Bulgarian northwest 😉.

Another point that came up was the role of the site pharmacist, for sites that have an on-site pharmacy obviously. Again, the IAL inspector asked what precisely was the role of the pharmacist on site, since their signature was not present on any preparation/dispensation records. My colleague calmly explained that he cannot tell the PI who will do what in his own site team, and that the PI's signature was indeed present on all records. He ended up having a minor finding, and although the inspector agreed this is not against compliance, he simply did not like the fact that the site pharmacist was not involved in the study, while still being delegated.

And now you are ready (as ready as someone could be) to conquer your first audit with confidence!

While audits can be stressful regardless of how well prepared you are, it's important to keep calm, respond with professionalism, and stay open to feedback. After all, if you are 100% sure you have given it your best, there's no need to worry. In general, audits are a good thing as they ensure the quality of your work. In the worst case scenario, they can still be great learning experiences 😉.