When working in the field of clinical trials, safety must be paramount in everything we do. We have to work hard to ensure that all aspects of the trial have safeguards to ensure all participants are safe during the trial and to enable ongoing safety when new treatments reach clinics. In the UK and indeed, world-wide, stakeholders involved in clinical trials aim for consistent national data collection on safety and efficacy. This ensures that when treatments reach clinical practice that any potential harm has been identified and mitigated against.
The last thing we want or need is for adverse events in a clinical trial to put off potential participants. One of the most high-profile drug trial disasters in history was the ‘Elephant Man’ drug trial in 2006, at Northwick Park hospital in London, so called due to the massive swelling and organ failure that occurred, whereby 6 men were treated in intensive care following an unpredicted ‘cytokine storm’ which was not seen in the animal testing phase of the trial. The six men survived, albeit with life changing injuries, the pharmaceutical company went bankrupt, but lessons were learned. It was a first-man-in study and all 6 were dosed at the same time via injection thereby giving all the drug at once – this would not happen now and a much more cautious approach to dosing is taken with low dose, going higher via infusion rather than injection and dosing one volunteer at a time.
Recruitment
A first safety step, is using approved and ethically sound recruitment to trials initiatives such as Join Dementia Research [1] (JDR). This ensures that initially, the right people, with the right characteristics are approached for inclusion in a dementia trial. In Scotland, we have both JDR and Permission to Contact, which enables us to ensure that participants have already agreed to be contacted about clinical trials and we have permission to access their medical records for screening purposes, allowing an extra safety step in ensuring the right person with the required characteristics are invited for inclusion in specific clinical trials.
Creating these trial-ready cohorts for prevention and intervention studies demands careful attention to consent, burden, and inclusion, ensuring participants understand long timelines and uncertain benefits. Altruism may be prevalent but this doesn’t mean a compromise on safety of that willing participant.
The trial team
The team must be sure they can deliver pathways for rapid imaging, lab monitoring, and adverse event follow-up so safety signals are captured and acted on promptly. The team must ensure they have all the necessary staff to conduct the clinical trial and that everyone is well versed on safety issues including having completed their GCP (Good Clinical Practice [2]) training and that it is up to date with certification to prove this. This ensures that everyone is following the international standards for clinical trials and that the participants rights, safety and well being are being looked after by every member of the study team.
PreScreening
Through the identification of potential participants, there has to be a degree of prescreening to ensure we screen out those who would not fit the criteria due to co-morbidities or concurrent prescribed or over the counter medications. Some trials will not allow someone who has previously been involved in a drug trial to take part in another, within a certain time frame. We need to check that the person is eligible for the study at hand. This also helps to manage unrealistic expectations of being included in a trial.
Screening
Prior to the first screening visit, the study team send study information to the potential participant to digest in their own time and to enable them to ask any questions of the team when they come for their first screening visit. It enables people to decide if they want to be involved before the first face-to-face visit.
Once invited and accepted to take part in a trial there is a rigorous screening process which starts with the least invasive procedures. This is to save both time and money plus keeps the procedures for the participant to the minimum necessary. Firstly, they have an opportunity to ask any questions about the study of the study doctor. Secondly, there would be a memory test or assessment to ensure they meet the inclusion criteria – if they fail this then it is relatively easy for them to bow out without having had any other invasive procedure. If they are still eligible for the trial they will have blood and urine samples taken. This allows any exclusions following the sample to be discussed ie a low vitamin B12 would sometime exclude someone but this can be remedied by prescribing supplements and retest a few months later if the protocol allows.
Lastly, procedures such as MRI, lumbar puncture or PeT scans would be performed last as they are the most invasive assessments and costly. Any anomalies found during any of the scans or procedures would be flagged to the NHS GP or clinician and followed up via the NHS. This will be explained before any procedures are carried out.
There are other safety considerations during a drug trial including: a strict adherence to the protocol; Knowing what to do if there are anomalies at any stage; building a relationship with the sponsor to ensure safety reporting is done rapidly; getting to know the participant and their carer so that if there are any important changes, at any time, they know that the team can be contacted and are trusted; Ensuring the participant and their carer understands that informing the team about any changes in their health or well being, no matter how insignificant they may seem at the time, is of utmost importance; taking their study drugs at the times stated and returning any unused drugs at each visit.
The safety of the participant is of utmost importance at all times during a clinical trial and especially when it involved investigational medicinal products. The study team must ensure that all procedures are followed and everyone is clear of their role during the trial. This can help to ensure that the trial is run with minimal risk to the participants who have willingly given their time and efforts to being involved in the study, for which we, as researchers, are extremely grateful.
Dr Emma Law
Author
Dr Emma Law [3]is Strategic Manager for the The Neuroprogressive and Dementia Network in Scotland. Emma has 13 years experience as a Clinical Trails Network Manager and over 35 years experience as a Nurse, many of which were spent in the delivery of Clinical Research Trials. Emma completed her PhD and is passionate about giving people living with dementia and their carers access to participate in research.