Supporting Clinical Trials in Patients With an Integrated Site Management Organization
The first question that comes to mind in discussing a Site Management Organization (SMO) SMO is ‘why is it necessary’? In an attempt to shorten drug development time and lower the resulting cost, patients are being included more and more in early phase (phase I and II) clinical trials, often in combined healthy volunteer/patient studies. The addition of patients to these early phase protocols requires the CRO to develop a network of sites and investigators who are able to successfully enroll the right patient population in order to conduct these trials.
For potential investigator sites that have the necessary patient pool, but lack the required staff, clinical research experience, or time, the SMO can provide a multidisciplinary team for on-site support. The additional benefit to the sponsor is the assurance that the study managed by the SMO team at the different sites is conducted with the same high quality SGS standards as can be expected. It is useful to keep in mind that not just early phase trials benefit from the SMO organization, but also late phase clinical trials. In the following examples of clinical trials performed by SGS we demonstrate how the SMO can accommodate several types of on-site support requests.
The aim of SGS’s SMO department is to facilitate patient recruitment for early phase clinical trials through external sites and, if needed, to support the external site in managing and executing the clinical trial. In the following case studies including phase I/IIa schizophrenia, dialysis and Influenza vaccination studies, we will see how an SMO can support efficiently the success of patient clinical trials.
Example 1: Phase I/IIA Schizophrenia Study
The first case is a phase I/IIa proof-of-concept trial in the treatment of schizophrenia. The study’s objective was to explore the efficacy and safety of the study medication in schizophrenic patients with residual symptoms treated with stable antipsychotic treatment. The sponsor had already established contacts with specialized psychiatric centres, but was faced with slow recruitment.
In order to explore alternative recruitment options the sponsor requested that SGS perform a thorough recruitment feasibility study. The SMO team contacted its established network of pharmacists and general physicians to determine the frequency of use of the protocol required antipsychotic background treatment in the community. The feasibility assessment revealed a very limited number of prescriptions were coming to the contacted pharmacies’ counters. It was concluded that the required patients could not be recruited within the community and had to be sought in psychiatric centres. This demonstrates the importance of study feasibility to endorse recruitment strategies. The main source of patient recruitment remained the pre-established contact between the sponsor and specialist/professors in psychiatric centres. However, a lack of resources and time at the specialized centres were identified as two significant factors hampering recruitment and hence, the SMO services were required.
In this case the psychiatric centres functioned as external sites with the specialists as Principal Investigators and the sponsor delivered their own Project Leader. The SMO support services requested by the sponsor included: trial coordination, execution of the trial and support in entering the study data in the case report forms (CRF). The challenge of this study organization was to execute a trial running at different sites without fixed days for drug administration and without knowing which intake patient would be suitable for screening. The solution SGS offered was a team consisting of a Clinical Research Coordinator (CRC), two Study Nurses and a Clinical Trial assistant for data entry. This team was able to travel to the site whenever an eligible patient was identified at one of the participating psychiatric centres. The keys for success in this specific case was the team’s flexibility, the experience of the CRC in psychiatry and the excellent communication with the sites in order to identify, in advance, a potential patient. As of publication, the trial is still ongoing and the organization is operating successfully. Eight patients were randomized in fives month’s time, which is a recruitment rate far above the sponsor’s expectation. Meanwhile, the same sponsor has made a second request for similar support.
Example 2: Phase I Dialysis Study
In 2011, SGS managed a phase I trial in dialysis patients. The purpose of the study was to evaluate the pharmacokinetics and safety of an injectable contrast agent in chronic renal failure patients requiring haemodialysis treatment. In order to establish a recruitment target, the SMO team conducted a feasibility study. A network of nephrologists and a collaborating nephro-dialysis centre were approached, and the number of recruitment potential was discussed, as were potential challenges of study design.
The SMO support services requested by the sponsor included: protocol review, preparation of the ethics and regulatory submission, patient screening, randomization, trial coordination and support in entering the study data in the case report forms.
The management of the project turned into very efficient collaboration between SGS’s own research unit, SGS’s SMO and external nephrologists. Each time a potential patient was identified by the specialist, he/she was referred to SGS’s research unit where they were screened by the SGS CRP, working as a co-investigator in the study. When the patient was found to be eligible, the CRC contacted the dialysis centre to establish a schedule suitable to both patient and centre. The trial itself was conduct is by the dialysis centre. All administrative tasks were carried out by the SGS team.
The SMO Coordinator liaised with the collaborating nephrologists, ensured the contracts were drawn up in time, provided the specialist with all the necessary information and followed up on the recruitment ensuring the committed target was met.
The challenges faced by the SMO included managing the large the number of collaborating players (i.e. the referring nephrologists, the internal staff and the dialysis centre) and achieving the recruitment target set by the sponsor. Excellent communication and organization, in addition to sufficient training of the staff at the dialysis centre were key components in the execution of this project. The recruitment goal was successfully met and the trial was closed with twelve patients enrolled in the targeted four month period.
Example 3: Phase III Influenza Vaccination Study
Another example of SMO services can be demonstrated through a phase III Influenza vaccination trial in elderly people. The international multi-centre study sought to compare the immunogenicity of an intradermally administered study vaccine to the intramuscular reference vaccine over a period of three years.
In order to recruit 200 healthy elderly volunteers, SGS collaborated with five general physician (GP) practices in close proximity to the SMO operating center in Antwerp, Belgium. Each GP became a Principal Investigator for their own site, but were supported by an SGS Study Nurse and CTA. The Study Nurse administered the vaccines and the CTA was responsible for the administrative matters. At all the GP sites, the study was conducted in accordance to SGS Standard Operating Procedures. Two key challenges included: first, the need for fast sample handling and secondly a potentially high drop-out rate during the 3 year study period – co-morbidity and natural death were within the normal expectations in this elderly study population. As a solution to the fast sample requirement, a mobile clinical unit was commissioned. This mobile unit is a van with power generating capacities and has a fridge, freezer, bed, ECG device, and centrifuge which allow patient samples to be taken at external sites with limited use of the collaborating physicians’ resources. Samples were subsequently brought to the subcontracted lab. To cope with the expected high drop-out rate the SMO team ensured that the retention of volunteers was maximized at each site. Having patient volunteers’ return visits scheduled at the familiar and convenient environment of their own GP’s practice proved to be a successful retention measure.
Meeting increasing sponsor demand to include patients in early phase clinical trials requires cooperation from key players including the CRO and external sites. The Site Management Organization at SGS was established to develop custom solutions to meet the specific needs of each new trial, and to ensure that patient recruitment and the subsequent support services are handled seamlessly.
SGS Life Science Services is a leading contract service organization providing clinical research, analytical development, biologics characterization, biosafety, and quality control testing. Delivering solutions for bio-pharmaceutical companies, SGS provides clinical trial management (Phase I to IV) services encompassing clinical project management and monitoring, data management, biostatistics, and regulatory consultancy. For a qualitative and faster patient recruitment across Americas and Europe, clients can count on SGS’s large data base of investigators and key opinion leaders with an high therapeutic expertise in Infectious Disease & HIV/HCV, Vaccines, Oncology and Respiratory.
Katrien Timmermans, MD
Life Science Services
Head Feasibility and SMO Europe - Clinical Research