By Soon Wen Xian, a medical graduate from Volgograd State Medical University, a Clinical Research Associate at an international pharmaceutical organization based in Singapore.
There are many stages in a clinical trial, for example: feasibility study, start up, active recruitment stage, maintenance stage and study closure. Each stage of a trial is important, but the recruitment process is undeniably the most important part. Because if there is no patient being recruited, there will be no data to analyse and without data, the trial will not meet any objectives. That is why recruitment process plays a very important role in ensuring a successful clinical trial. Recruitment rate is almost always the main issue in a trial. If we can speed up the recruitment rate, not only would we have the results faster, we would also be able to reduce the cost of the trial. In order to make recruitment process a successful one, both site member and sponsor must know their roles well. For this issue, I would like to share how we can make a trial recruitment process easier, faster, and more effective.
What can a sponsor do to speed up the recruitment process?
In my opinion, a CRA (Clinical Research Associate) should discuss recruitment plan with the site not only during the feasibility study but also during submission or SIV (site initiation visit). During feasibility study, a CRA should understand where potential subjects can be located. They may be in the emergency department, found during clinic day or maybe there are some potential subjects that will be taken in by other departments. If the potential subject was taken in by other departments, CRAs can possibly create a brochure or poster to be given to the related department. By having these brochures around, this might remind the department to refer the potential subject to the investigator team. The brochure or poster can be displayed at the department wall or on the doctor’s table. If the site approves of the idea, the CRA will have to discuss with the sponsor as the brochure and poster may need to be sent to the ethics committee for approval.
Other than brochures or posters, a CRA could also suggest for a briefing session with the relevant department medical staff. Sometimes, investigators may not be able to spare time for a presentation, but a CRA can proactively get the investigator’s approval to approach the related department. In Malaysia, all departments have CME session and CRAs can take about 15 minutes during the meeting to present on the trial and request the department to refer potential subjects to their investigators.
The most effective way to get referral patients from other departments is to get 1 or 2 of the doctors there to be involved as sub-investigators. This will make the doctors feel more involved in the trial and they will be more proactive in looking for potential subjects. This will also create a good environment at the site and encourage more doctors to be interested and involved in clinical research. All this while, clinical research always seem like is a secret mission where – other than study team members – all the other doctors have no chance to get involved. By changing the environment, this will create awareness of clinical research in the hospital.
If an investigator suggests approaching other hospitals for referral, a CRA should always have the referral letter template with him/her. Investigators will only need to fill up the template and print the letter with the site letter head, then it will be ready to send to other hospitals. Most of the time, the letter does not need approval from the ethics committee.
Other than providing support to site on the recruitment process, a CRA should also constantly share the recruitment status of the country and region. The status should be sent to all sites on a monthly basis or fortnightly. When sites received the email, they will know that the CRA is monitoring the recruitment process closely. If there is any site in Malaysia that has recruited a subject, the CRA should share the news to all sites acknowledging the effort. This method helps a lot as it will create awareness among all the sites in Malaysia.
What can site staff do to improve recruitment process?
Recruitment process depends on the protocol design. Sometimes, the protocol design allows site staff to do pre-screening before the trial even started. This is because the potential subject may be having a follow up visit to the site. Site staff should be able to review the medical note to allocate those potential subjects. Once the trial is ready for screening, site staff can start contacting subjects to arrange for screening visit. This is the fastest and most effective way to screen as the subject is already in the patient bank.
The most challenging part of recruitment process are those protocol designs that will allow only the newly diagnosed patients to be recruited. In this case, sites will have to wait for the potential subject to come on a random day and site staff must catch the subject during the visit. Another challenging way to recruit is for the site staff to review all clinic patients every day so they do not miss any of them. Other than this, investigators should arrange 2 days in a week to meet up with all the doctors in the department to discuss regarding the criteria of the patient for the recruitment. This will make the whole department aware that a trial is actively looking for patient.
During the process, it is recommended that Study Coordinators (SC) document the patients they have seen and state why certain patients are not eligible. This is very important because firstly, this is to document the efforts that site staff had put in. Second, from the list of patients, we can analyse which criteria is the most challenging for the recruitment process and thirdly, some trial will even pay for this effort!
Site should randomize a subject within 3 weeks after site is ready. If site is still facing difficulty to recruit subjects, a meeting should be scheduled between the sponsor and site staff. During the meeting, CRA and site staff should discuss on the list of patients they have pre-screened but are not eligible. Sometimes, site staff may misinterpret causing site to lose potential subjects. Other than reviewing the patient list, CRAs should also share the recruitment status of other sites. It may be that other sites are able to recruit patients and have found a useful method to allocate potential patients. Plus, by sharing other sites’ recruitment status, this will encourage the lesser recruiting sites to be more aggressive in their recruitment process.
What other ways can we try in Malaysia to improve recruitment process?
In my opinion, we should try to opt in using social media to share what kind of trials are currently available in Malaysia. As we know, all trials conducted in Malaysia must be registered in the NMRR website and this is a public website. Some of the trial information are freely available to read in the website. If there is an organization that can actively promote in social media on the kind of trials that are currently recruiting in Malaysia, this will really help in boosting the recruitment rate as many of our citizens do not know about clinical research and do not know how to get involved in clinical trials. Clinical research can really benefit patients especially when it comes to cancer patients. Current treatment for cancer disease can be very expensive and may not be effective but patients who are being treated in a clinical trial are treated for free and may be using a more effective treatment than currently available. Moreover, patients will be closely monitored by investigators as this is required by the protocol. Usually the patient will undergo an imaging scan for tumour status every 9 weeks and will have blood test every 3 weeks. For patients that are not participating in clinical trials, they may not be having this kind of structured and routine procedure as these procedures are costly.
Recruitment is everything for a trial and if we can perform well on the recruitment process, more trials will come to Malaysia.