By: Eka Windari R., I Wayan Adi Pranata, Lois E. Bang, Melinda Setiyaningrum, Regina Septiana, Nur Latifa Hanum, Restu Amalia, Riza Danu Dewantara

The Indonesia InVITE study is preparing for a Site Closeout Visit (SCV) scheduled for February 2025. The Secretariat and Sites team are coordinating to ensure all study documents and supplies are ready for SCV activities. The first shipment of serum specimens, totaling approximately 1,053 serum vials from Visits 1, 2, 3, and symptomatic visits (13 cryoboxes), was successfully sent via World Courier on September 23, 2024, and arrived at the Central Laboratory (Frederick National Lab USA) on September 27, 2024, without issues. A second shipment, containing 1,046 serum vials (13 cryoboxes), was sent on October 14, 2024, and reached the Central Laboratory on October 19, 2024, after an unexpected airline delay from Jakarta to the US. To prevent the specimens from thawing, the Central Laboratory team arranged for dry ice replenishment upon arrival at John F. Kennedy International Airport in New York. The specimens remained frozen, with an average recorded temperature of -81.5°C (SD ± 2.7°C). The Central Laboratory team is currently assessing the specimens’ integrity and packaging suitability for future shipments and has requested the shipment video from the INA-RESPOND Reference Laboratory team. Additionally, the mid-turbinate swab specimen shipment is still under discussion between the Secretariat and NIAID Team due to poliovirus eradication requirements for RNA extraction.

After the Indonesia InVITE team recently bid farewell to dr. Natalia from Site 02 (Maumere), they will soon say goodbye to dr. Regina Septiana, a dedicated Research Assistant (RA) from Site 03 (Banjarmasin), as her contract ends. In this newsletter, dr. Regina shares her nearly three-year experience working as an RA at Site 03 for the INA-PROACTIVE Study, starting in February 2021.

Figure 1. Site 03 team (left to right): Lutfia Rahimah, SKM (LT), Silvia Rahmi Astuti, Str, Kes (LT), dr. Regina Septiana (RA), dr. Rizka Dwi Puteri (RA), Tiya Saraswati (CRA), dr. Wiwit Agung SNC, Sp.PD, K-Ger (PI), dr. Maimunah (NSC member), dr. Rahmawati, Sp.PK (Co -PI), dr. Dewi Rizki Agustina, Sp.PD, FINASIM (Co-PI).

Site 03 became a top choice when the InVITE study expanded its recruitment target from 500 to 700 participants, thanks to its strong history of collaboration with INA-RESPOND from the INA-PROACTIVE study. dr. Wiwit Agung SNC, Sp.PD, K-Ger, served as the Site Principal Investigator (PI) for both the INA-PROACTIVE and InVITE studies. Known for her commitment, dr. Wiwit encour-aged RAs to engage actively in scientific writing beyond just conducting the study. At Site 03, dr. Regina worked closely with Co-PIs, dr. Dewi Rizki Agustina, Sp.PD, FINASIM, and dr. Rahmawati, Sp.PK, and also co-partnered with dr. Rizka Dwi Putri, who served as an RA from January 2022 until August 2023.

A site preparation visit and training session were held on January 6-7, 2022, after which subject recruitment began in February 2022 at Kayutangi and Cempaka Public Health Centers (Puskesmas). dr. Regina faced challenges in recruitment, such as individuals perceiving little personal benefit, educational barriers to understanding the study’s purpose, long travel distances for follow-up visits, scheduling conflicts, and fear of blood draws. Despite these challenges, Site 03 successfully completed recruitment within two months, reaching the target of 130 subjects.

During the follow-up phase, dr. Regina was responsible for contacting participants for their scheduled visits, conducted at the Clinical Pathology Laboratory with support from the Laboratory Technician (LT). Most participants cooperated with follow-up requests, and the LT’s experience made the process smooth. However, some participants were anxious during specimen collection and required reassurance. Several participants expressed interest in their local SARS-CoV-2 anti-body results, frequently inquiring about them during visits or via WhatsApp.

Figure 2. Laboratory activities.


Figure 3. INA-RESPOND Secretariat Room at Site 03 and specimen shipment activities at the hospital laboratory.

In her role, dr. Regina conducted bi-weekly calls to monitor participants for COVID-19 symptoms and encourage symptomatic visits when necessary. Some participants reported symptoms but were hesitant to attend symptomatic visits, fearing a positive result might impact their job or invite social stigma. The bi-weekly calls were sometimes challenging as not all participants had personal mobile phones, requiring dr. Regina to reach out to family members or use SMS and calls instead of WhatsApp.

dr. Regina and her team also encountered challenges in specimen collection and transport due to the distance between the Public Health Center and the hospital. The LT periodically transported samples using a cool bag with ice packs, and after each follow-up, samples were sent to the INA-RESPOND Reference Laboratory at Tangerang Hospital. dr. Regina and the LT managed sample shipment preparations, including verification, packaging, and documentation. Coordinating flight schedules from Banjarmasin to Tangerang was often challenging, requiring early arrival at the hospital. Flights were mostly timely, ensuring samples arrived frozen. The team was trained to use the Credo Cube instead of dry ice for better cold chain management.

Personally, dr. Regina found her experience in the InVITE study both exciting and challenging, especially due to its focus on COVID-19. She gained valuable insights into COVID-19 and vaccine effects and appreciated the support from the INA-RESPOND teams. A memorable moment for dr. Regina and the Secretariat was her participation in a “Phone Call” manuscript plan, where she presented her experience conducting bi-weekly calls in English. Her presentation was highly praised, though the manuscript plan was eventually canceled due to data harmonization challenges. dr. Regina’s effort is commendable, and we fully support her future scientific pursuits.

Currently, Site 03 is preparing for the SCV. After a seven-year collaboration with INA-RESPOND that began with the INA104-PROACTIVE study and continued with the InVITE study, the Site 03 team expresses heartfelt gratitude to INA-RESPOND for the opportunity to work on studies with high standards. The team has gained extensive knowledge in informed consent procedures, sample collection, and document management. They feel appreciated for their involvement in scientific writing and publication opportunities based on research data.

The InVITE study at Site 03 was a success, providing valuable insights to the INA-RESPOND Secretariat. We extend our deep gratitude to the Site 03 team for their cooperation, patience, flexibility, and hard work. ‘Thank you’s and apologies might not be enough to show how grateful we are for the Site 03 team’s patience, flexibility, and hard work during the study. We’re excited to work with Ansari Saleh Hospital on more INA-RESPOND projects in the future and wish the entire Site 03 team continued success. Special thanks to dr. Regina — we are truly grateful for your dedication and hard work throughout the InVITE journey, especially regarding the careful study data completion with minor queries and smooth communication. This experience will indeed become a fond memory. We wish you happiness and success in your next endeavor, and we hope our paths will cross again.

By: Eka Windari R., I Wayan Adi Pranata, Lois E. Bang, Melinda Setiyaningrum, Regina Septiana, Nur Latifa Hanum, Restu Amalia, Riza Danu Dewantara

The INA-PROACTIVE study team is finalizing the study report for submission to the Ethics Committees (EC) alongside manuscript preparation. A clinical study report (CSR) provides a comprehensive summary of studies involving human subjects, integrating clinical and statistical analyses. Upon study completion, the Sponsor prepares and submits the CSR to regulatory agencies, and the Investigator provides the institution and EC with a study summary.

Figure ref: Cronin H, Hamblin F, Goldenberg NA. Operationalizing Good Clinical Practice

 

In December 2023, after closing all INA-PROACTIVE study sites, the EC was notified of the study close-out activities and provided an interim study report, with the final report expected by year-end.

Summary of the Final Study Report

The INA-PROACTIVE study was conducted by 19 sites across Indonesia, with 15 using a Central EC and four using a Local EC. Initial approval was granted on January 18, 2018, with one protocol amendment in June 2018. Each site obtained hospital study permits before starting. The first site activation occurred on March 12, 2018, followed by screening and enrollment. At first, the Central EC responsible for approving and evaluating the study was the Balitbangkes, MoH EC. However, during the study, the Balitbangkes, MoH EC underwent restructuring and ceased operations. Consequently, the Central EC was changed to the FK-UI, RSCM EC. All study activities, from screening to the last patient’s final visit, took place between January 10, 2018, and May 31, 2023.

Of the 4,336 subjects enrolled, 3,496 completed the study, and 840 withdrew due to reasons like relocation, negative HIV status, and death. Additionally, 57 subjects transferred between sites, resulting in a retention rate of 86.76%.

Collected specimens included plasma and buffy coat samples, managed per INA-RESPOND proto-cols. Only three adverse events (AEs) related to blood collection were reported, with no Serious AEs (SAEs) or Unanticipated Problems. There were 757 Reportable Events (REs) from disease complications, including 251 deaths, 427 hospitalizations, and 76 Important Medical Events (IMEs) such as COVID-19.

Clinical research associates (CRAs) conducted 108 on-site and remote visits, ensuring protocol and Good Clinical Practice compliance. Minor protocol deviations totaled 1,598, with 7 major deviations, all reviewed, reported to the EC, and corrected. Site close-out occurred from March to October 2023, with study documents securely stored by Indo Arsip.

Now focused on study results, Clinical Research Site Specialists (CRSS) collaborate with Data Management and Scientific Teams to reconcile safety reports, especially IMEs related to COVID-19. The Statistician is conducting data analyses for the Scientific Team to determine the study conclusions outlined in the protocol.