Clinical research is essential to the future of healthcare and the wellbeing of patients, no matter what health condition they face. Many patients who choose to participate in clinical research studies in ophthalmology find optimism in discovering novel medicines to help improve their visual status, depending on the eye conditions that have plagued them. The setup, delivery, organisation, recruitment and management of these trials cost thousands of pounds. But what role does imaging play, and what is involved? I’ll go over all the challenges that go into making clinical research successful in this article.
Good clinical practice/curriculum vitae (GCP/CV)
Before anyone can conduct or take part within clinical research, you are required to obtain a ‘good clinical practice’ (GCP) certificate. This is the international standard set by the National Institute for Health and Care Research (NIHR), the governing body who oversee clinical research trials. This ensures that the rights, safety and wellbeing of trial participants are protected, and that the data generated is credible and reliable [1]. A curriculum vitae (CV) must be created following the GCP certificate. This proves your credentials and clinical research experience. The experience identifies the clinical trials you have participated in. You might indicate on your resume that you have recently received certification to participate in clinical research if you have no prior research experience. The CV needs to be dated, signed with wet ink and include the date of your GCP certificate.
Clinical investigator (CI)
A clinical investigator is a person who conducts a clinical trial or research study. The investigator may assist in developing and implementing the study’s protocol (plan), keeping an eye on its safety, gathering and analysing data and reporting its findings. Physicians, scientists, nurses and other research personnel are examples of investigators. Multiple investigators may be involved in some clinical trials or research investigations. The principal investigator (PI), who oversees the entire study, is typically one of the investigators [2].
Principal investigator (PI)
The PI is the researcher, typically a physician or other medical expert, who oversees the clinical research team and, in conjunction with the other team members, routinely assesses the safety and efficacy of the study by monitoring the health of study participants. In accordance with existing rules and regulations as well as institutional policy guiding the conduct of clinical research, a PI is principally in charge of the planning, execution and management of a research grant, cooperative agreement or other funded study [3].
Sub-investigators (SI)
Under the direction of the PI, sub-investigators (SIs), sometimes referred to as co-investigators, are crucial to clinical research. Like the PI, the SI is usually a doctor with experience in the therapeutic area of the clinical trial. The PI must formally assign them tasks and provide them with the necessary training to fulfil the demands of the study. An SI supports the PI’s work and ensures the trial runs smoothly by sharing the workload and providing additional specialised knowledge. Their participation is essential for overseeing patient care, guaranteeing regulatory compliance and preserving the calibre of the data gathered, all of which contribute to the clinical trial’s overall success [4].
Clinical research nurse (CRN)
A clinical research nurse is a registered nurse who oversees and provides patient care in clinical trials. They serve as an essential liaison between patients, physicians and research teams to guarantee that studies (testing new medications, devices or treatments) are carried out safely, ethically and in accordance with stringent protocols, with an emphasis on participant safety, accurate data collection and education. They ensure high-quality, patient-centred care by recruiting participants, administering therapies, gathering samples (such as blood), keeping an eye on vital signs, recording events and giving patients essential support and information throughout the research process.
Clinical trials co-ordinator (CTC)
For research participants, clinical trial co-ordinators serve as their primary point of contact. They are essential for guaranteeing participants’ safety and wellbeing during their clinical trial experience. Additionally, co-ordinators serve as the primary point of contact with the project management team of the study sponsor. They can participate in a variety of study setup tasks at the trial site, including managing the study there, including scheduling meetings and invoices, as well as preparing the site study file and source papers and submitting ethics [5].
Optometrists
By bridging the gap between patient care and scientific discovery and advancing eyecare through evidence-based practice, optometrists play a crucial role in clinical research. They can act as PIs or SIs, especially in trials based on pharmaceuticals, medical devices or within diseases such as diabetic retinopathy, glaucoma or macular degeneration. Their roles include routine and complex refractions, visual field assessments including microperimetry as well as full-field microperimetry and colour vision assessments along with other psychophysical assessments of a patient’s visual function.
Pharmacy
Many clinical trials include the testing of new drugs. As a crucial link between drug development and patient safety, pharmacists ensure the safe handling, storage and dispensing of investigational medicines, ensure protocol compliance and maintain accurate records. They also manage complex logistics, such as the cold chain for innovative medicines, and work with research teams to uphold ethical and regulatory standards. Their knowledge ensures that trial medications are administered appropriately, with quality and integrity, safeguarding both participants and data [6].
Clinical data manager (CDM)
A person who guarantees the confidentiality, accuracy and integrity of data gathered during clinical trials is known as a clinical data manager. To provide accurate findings, they are responsible for designing and managing databases, setting standards for data collecting, keeping an eye on quality and resolving inconsistencies. They collaborate closely with biostatisticians, clinical researchers and regulatory teams to convert unprocessed trial data into verified information for medication development and regulatory filings. Using specialist software to handle massive amounts of patient data, clinical data managers also guarantee adherence to international norms and good clinical practice. They are essential in speeding up medical research, enhancing patient safety and facilitating the approval of novel treatments by protecting data quality [7].
Photographers
Accurate optical coherence tomography (OCT) scans, colour fundus photography (FP), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), fundus autofluorescence images, OCT angiography, slit lamp images and, depending on the type of study, ultra-wide field images like FP or FFA/ICGA may be required. Reading centres give the strict image protocols that photographers must follow. In situations when image interpretation is crucial, reading centres offer centralised, objective analysis of medical data, particularly photographs, to guarantee consistency, lessen bias and maintain high data quality. Every photographer participating in the clinical study must complete a certification process to maintain good data quality. This is prior to them being able to take part in the clinical trial. One or two photographers are normally assigned to upload the images to the reading centre in a timely manner. This is usually done the same day as the images are captured. Reading centres can vary in the time to process the images but on average it is between 2–4 business days.
Setting up a clinical trial
In order to guarantee patient safety, scientific integrity and regulatory compliance, setting up a clinical research trial is a complicated, multi-stage procedure that calls for meticulous planning. Developing a thorough protocol, obtaining sponsorship, getting ethical and regulatory clearances from a research ethics committee (REC), choosing appropriate venues and creating a data management system are the most important tasks. For a full, detailed management of setting up a clinical trial, see the clinical trials toolkit diagram (Figure 1) courtesy of the NIHR.
Figure 1: The clinical trials toolkit roadmap.
Once everything is set up, one other relevant component within randomised clinical trials (RCT) is ‘blinding’ or ‘masking’. Masking techniques for research can be as complex as sham surgeries or as simple as giving a placebo tablet that looks exactly like the actual medication.
All participants are placed into a group. There are usually two types:
- The experimental group: the novel intervention or treatment being tested in the study is given to this group of participants [8].
- The control group: this set of participants is given a comparator intervention, which could be a placebo, the conventional treatment, or no intervention at all. To determine how effective the new treatment is, researchers compare the outcomes of the experimental group with those of the control group [8].
Some people are not aware of the treatment that the participants in the trial undergo. Preventing bias in the study’s findings is the aim. There are two main types of masked studies.
- In a single-blind (single-masked) study, the research staff is aware of the participants’ treatment group, but the participants do not [8].
- In a double-blind (double-masked) study, neither the research team nor the participants are aware of who has been allocated to each treatment group. The pharmacist is typically the only one who is aware of which treatment is being given to whom [8].
My experience
I have been involved within ophthalmic photography clinical research trials since 2017. They are rewarding but at the same time can be demanding, not only on the staff involved, but also on the constraints of the participants. Randomised clinical trials can vary in length depending on the study and what it’s trying to achieve. These can be from a few days/weeks up to five years. The length of an RCT is structured on phases.
Clinical trials are organised into four primary phases (0–III) to evaluate the safety, efficacy and dose of novel medicines. Phase IV is post-marketing research. A new medication cannot be licensed for public use unless these stages are finished in order [9].
Phase I
The duration of phase I research can range from a few days to many weeks. The medication will typically be evaluated on 20–80 healthy volunteers or patients under close observation. Information regarding the medication’s metabolism in human beings is gathered through these investigations. The data is utilised to determine the dosage that will be applied during the subsequent testing phase. Any adverse effects are noted, along with their type and intensity within a monitored clinical research environment or facility [9].
Phase II
Patients with the target disease (between 100–300) participate in phase II research. Here, the effectiveness of the medication will be examined in terms of how it affects the disease’s symptoms and indicators, and additional data on the medication’s safety will be gathered. In certain studies, the novel medication is contrasted with the most effective treatment currently in use; in other trials, it is contrasted with a placebo, which is an inert substance. The trial will frequently be conducted in a ‘double blind’ fashion in either scenario. This makes it easier to distinguish between a medication’s physical effects and any other effects that could arise from a patient believing a medication will have a specific effect and then really experiencing it (placebo effect). Additionally, problems that might require more investigation in later research are noted. This aids in determining the dosage schedule for the last round of clinical trials prior to the new medication’s licensing application [9].
Phase III
Phase III trials are conducted on a far greater scale. The decision to start this stage is taken after the safety profile of the medication has been established to the greatest extent possible and the results from the earlier stages have been recorded and observed to suggest that the medication may be effective. Phase III trials are intended to collect proof of the medication’s effectiveness in particular indications and to gain a deeper understanding of its safety profile. A randomised code is used to assign patients to their treatments; some will receive the new medication, while others will receive a placebo or an existing treatment. The medication is usually given to thousands of patients during this phase, which can take several years to finish [9].
Examples
As I’ve mentioned, RCTs need a large number of participants to be successful. Both the patients who take part in these trials and the related Trust may benefit greatly from their outcomes. Many eye problems might not be able to be treated with new treatments if we didn’t have participants. Here are two examples of two different trials:
Figure 2: Example 1 – beginning of phase II, colour fundus.
Figure 3: Example 1 – beginning of phase II, OCT, screening visit.
Figure 4: Example 1 – end of phase II, colour fundus.
Figure 5: Example 1 – end of phase II, OCT, end of trial visit.
The first was a phase II trial to test a new intravitreal treatment for diabetic macular oedema. The images shown are from the start of the trial (see Figure 2 and Figure 3) and the end of the trial (see Figure 4 and Figure 5).
The next trial was another phase II trial again testing a new intravitreal treatment for central retinal vein occlusion. Again, from the start of the trial (see Figure 6 and Figure 7) and the end of the trial (see Figure 8 and Figure 9).
Figure 6: Example 2 – beginning of phase II, colour fundus.
Figure 7: Example 2 – beginning of phase II, OCT, screening visit.
Figure 8: Example 2 – end of phase II, colour fundus.
Figure 9: Example 2 – end of phase II, OCT, end of trial visit.
The results speak for themselves. The drug used was the same for both trials but for different conditions and was successfully licensed to be used. You will often find that a certain new treatment drug will be trialled against many different eye conditions.
To conclude, I would wholeheartedly recommend getting involved in ophthalmic research. I thoroughly enjoy it and it’s a great learning opportunity.
References
1. www.nihr.ac.uk/career-development/clinical
-research-courses-and-support/good-clinical-practice
2. https://toolkit.ncats.nih.gov/glossary/clinical-investigator
3. https://toolkit.ncats.nih.gov/glossary/principal-investigator
4. www.zanteris.com/the-essential-collaboration
-the-role-of-principal-and-sub-investigators-in-clinical-trials/
5. https://genesisresearchservices.com/
clinical-trials-the-role-of-the-coordinator/
6. www.abpi.org.uk/careers/working-in-the-industry/
research-and-development/pharmacy/pharmacists
-in-research-and-development/
7. https://em-lyon.com/en/student/guides/jobs/clinica
l-data-manager#:~:text=Their%20role%20is%20to%20design,
Data%20analysis%20and%20structuring
8. https://weillcornell.org/news/here%E2%80%99s
-what-we-know-the-abcs-of-clinical-trial-terminology
9. www.abpi.org.uk/careers/working-in-the-industry/
research-and-development/clinical-studies/clinical-trials-work
[All links last accessed June 2026]
Declaration of competing interests: None declared.
