Exploring the Emotional Lived Experiences of Participants in First-in-Human Gene Therapy Clinical Trials
Main Article Content
Abstract
Gene therapy represents a revolutionary approach to treating genetic disorders, offering the potential for long-term cures through molecular interventions. Using a phenomenological research design grounded in Interpretative Phenomenological Analysis (IPA), this study investigates the lived emotional experiences of individuals participating in first-in-human gene therapy clinical trials. However, little is known about the subjective experiences of participants involved in such trials, particularly regarding their emotional, psychological, and ethical responses. The question arises: how do participants navigate the complex emotions of hope and fear while undergoing experimental treatments? Adopting a qualitative phenomenological methodology, data were collected through in-depth, semi-structured interviews with 12 participants and analyzed systematically following IPA procedures to capture meaning-making processes and experiential themes. The study identifies key themes such as hope, fear, and the transformation of identity, showing that participants grapple with both anticipation of therapeutic benefit and uncertainty about risks. The analysis reveals that the balance between hope and fear, as well as the shift in identity from patient to research subject, plays a crucial role in participants’ decision-making and coping strategies. These findings offer new insights into the emotional complexities of participating in clinical trials, highlighting the need for psychosocial support and improved informed consent processes. The study contributes to a deeper understanding of participants' lived experiences and provides methodological transparency regarding phenomenological inquiry in clinical trial contexts, offering a foundation for future research in clinical trial design and patient care.
Article Details
Section
References
Abou-Alfa, G. K., Macarulla, T., Javle, M., Kelley, R. K., Lubner, S. J., Adeva, J., Cleary, J. M., Catenacci, D. V., Borad, M. J., Bridgewater, J., Harris, W. P., Murphy, A. G., Oh, D.-Y., Whisenant, J., Lowery, M. A., Goyal, L., Shroff, R. T., El-Khoueiry, A. B., Fan, B., … Zhu, A. X. (2020). Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): A multicentre, randomised, double-blind, placebo-controlled, phase 3 study. The Lancet Oncology, 21(6), 796–807. Scopus. https://doi.org/10.1016/S1470-2045(20)30157-1
Alix-Panabières, C., & Pantel, K. (2021). Liquid biopsy: From discovery to clinical application. Cancer Discovery, 11(4), 858–873. Scopus. https://doi.org/10.1158/2159-8290.CD-20-1311
Awad, M. M., Liu, S., Rybkin, I. I., Arbour, K. C., Dilly, J., Zhu, V. W., Johnson, M. L., Heist, R. S., Patil, T., Riely, G. J., Jacobson, J. O., Yang, X., Persky, N. S., Root, D. E., Lowder, K. E., Feng, H., Zhang, S. S., Haigis, K. M., Hung, Y. P., … Aguirre, A. J. (2021). Acquired resistance to KRASG12C inhibition in cancer. New England Journal of Medicine, 384(25), 2382–2393. Scopus. https://doi.org/10.1056/NEJMoa2105281
Bidard, F.-C., Kaklamani, V. G., Neven, P., Streich, G., Montero, A. J., Forget, F., Mouret-Reynier, M.-A., Sohn, J., Taylor, D., Harnden, K. K., Khong, H., Kocsis, J., Dalenc, F., Dillon, P. M., Babu, S., Waters, S., Deleu, I., García-Sáenz, J. A., Bria, E., … Bardia, A. (2022). Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. Journal of Clinical Oncology, 32. Scopus. https://doi.org/10.1200/JCO.22.00338
Byrd, J. C., Hillmen, P., Ghia, P., Kater, A. P., Chanan-Khan, A., Furman, R. R., O’Brien, S., Nuri Yenerel, M., Illés, A., Kay, N., García-Marco, J. A., Mato, A., Pinilla-Ibarz, J., Seymour, J. F., Leprètre, S., Stilgenbauer, S., Robak, T., Rothbaum, W., Izumi, R., … Jurczak, W. (2021). Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial. Journal of Clinical Oncology, 39(31), 3441–3452. Scopus. https://doi.org/10.1200/JCO.21.01210
De Oliveira, D. M. P., Forde, B. M., Kidd, T. J., Harris, P. N. A., Schembri, M. A., Beatson, S. A., Paterson, D. L., & Walker, M. J. (2020). Antimicrobial resistance in ESKAPE pathogens. Clinical Microbiology Reviews, 33(3). Scopus. https://doi.org/10.1128/CMR.00181-19
DiNardo, C. D., Tiong, I. S., Quaglieri, A., MacRaild, S., Loghavi, S., Brown, F. C., Thijssen, R., Pomilio, G., Ivey, A., Salmon, J. M., Glytsou, C., Fleming, S. A., Zhang, Q., Ma, H., Patel, K. P., Kornblau, S. M., Xu, Z., Chua, C. C., Chen, X., … Wei, A. H. (2020). Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML. Blood, 135(11), 791–803. Scopus. https://doi.org/10.1182/BLOOD.2019003988
Doebele, R. C., Drilon, A., Paz-Ares, L., Siena, S., Shaw, A. T., Farago, A. F., Blakely, C. M., Seto, T., Cho, B. C., Tosi, D., Besse, B., Chawla, S. P., Bazhenova, L., Krauss, J. C., Chae, Y. K., Barve, M., Garrido-Laguna, I., Liu, S. V., Conkling, P., … Demetri, G. D. (2020). Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: Integrated analysis of three phase 1–2 trials. The Lancet Oncology, 21(2), 271–282. Scopus. https://doi.org/10.1016/S1470-2045(19)30691-6
Doḧner, H., Wei, A. H., Appelbaum, F. R., Craddock, C., DiNardo, C. D., Dombret, H., Ebert, B. L., Fenaux, P., Godley, L. A., Hasserjian, R. P., Larson, R. A., Levine, R. L., Miyazaki, Y., Niederwieser, D., Ossenkoppele, G., Röllig, C., Sierra, J., Stein, E. M., Tallman, M. S., … Löwenberg, B. (2022). Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood, 140(12), 1345–1377. Scopus. https://doi.org/10.1182/blood.2022016867
Frangoul, H., Altshuler, D., Cappellini, M. D., Chen, Y.-S., Domm, J., Eustace, B. K., Foell, J., de la Fuente, J., Grupp, S., Handgretinger, R., Ho, T. W., Kattamis, A., Kernytsky, A., Lekstrom-Himes, J., Li, A. M., Locatelli, F., Mapara, M. Y., de Montalembert, M., Rondelli, D., … Corbacioglu, S. (2021). CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. New England Journal of Medicine, 384(3), 252–260. Scopus. https://doi.org/10.1056/NEJMoa2031054
Goldbrunner, R., Stavrinou, P., Jenkinson, M. D., Sahm, F., Mawrin, C., Weber, D. C., Preusser, M., Minniti, G., Lund-Johansen, M., Lefranc, F., Houdart, E., Sallabanda, K., Le Rhun, E., Nieuwenhuizen, D., Tabatabai, G., Soffietti, R., & Weller, M. (2021). EANO guideline on the diagnosis and management of meningiomas. Neuro-Oncology, 23(11), 1821–1834. Scopus. https://doi.org/10.1093/neuonc/noab150
Gradishar, W. J., Anderson, B. O., Abraham, J., Aft, R., Agnese, D., Allison, K. H., Blair, S. L., Burstein, H. J., Dang, C., Elias, A. D., Giordano, S. H., Goetz, M. P., Goldstein, L. J., Isakoff, S. J., Krishnamurthy, J., Lyons, J., Marcom, P. K., Matro, J., Mayer, I. A., … Kumar, R. (2020). Breast cancer, version 3.2020. JNCCN Journal of the National Comprehensive Cancer Network, 18(4), 452–478. Scopus. https://doi.org/10.6004/jnccn.2020.0016
Hong, D. S., DuBois, S. G., Kummar, S., Farago, A. F., Albert, C. M., Rohrberg, K. S., van Tilburg, C. M., Nagasubramanian, R., Berlin, J. D., Federman, N., Mascarenhas, L., Geoerger, B., Dowlati, A., Pappo, A. S., Bielack, S., Doz, F., McDermott, R., Patel, J. D., Schilder, R. J., … Drilon, A. (2020). Larotrectinib in patients with TRK fusion-positive solid tumours: A pooled analysis of three phase 1/2 clinical trials. The Lancet Oncology, 21(4), 531–540. Scopus. https://doi.org/10.1016/S1470-2045(19)30856-3
Hong, D. S., Fakih, M., Strickler, J. H., Desai, J., Durm, G. A., Shapiro, G. I., Falchook, G. S., Price, T. J., Sacher, A., Denlinger, C. S., Bang, Y.-J., Dy, G. K., Krauss, J. C., Kuboki, Y., Kuo, J. C., Coveler, A. L., Park, K., Kim, T. W., Barlési, F., … Li, B. T. (2020). KrAsG12C inhibition with sotorasib in advanced solid tumors. New England Journal of Medicine, 383(13), 1207–1217. Scopus. https://doi.org/10.1056/NEJMoa1917239
Hosomi, Y., Morita, S., Sugawara, S., Kato, T., Fukuhara, T., Gemma, A., Takahashi, K., Fujita, Y., Harada, T., Minato, K., Takamura, K., Hagiwara, K., Kobayashi, K., Nukiwa, T., Inoue, A., Kudoh, S., Kurihara, M., Nagao, K., Nakai, Y., … Akai, M. (2020). Gefitinib alone versus gefitinib plus chemotherapy for non–small-cell lung cancer with mutated epidermal growth factor receptor: NEJ009 study. Journal of Clinical Oncology, 38(2), 115–123. Scopus. https://doi.org/10.1200/JCO.19.01488
Jánne, P. A., Riely, G. J., Gadgeel, S. M., Heist, R. S., Ignatius Ou, S.-H. I., Pacheco, J. M., Johnson, M. L., Sabari, J. K., Leventakos, K., Yau, E., Bazhenova, L., Negrão, M. V., Pennell, N. A., Zhang, J., Anderes, K., Der-Torossian, H., Kheoh, T., Velastegui, K., Yan, X., … Spira, A. I. (2022). Adagrasib in Non–Small-Cell Lung Cancer Harboring a KRASG12C Mutation. New England Journal of Medicine, 387(2), 120–131. Scopus. https://doi.org/10.1056/NEJMoa2204619
Kalinsky, K., Barlow, W. E., Gralow, J. R., Meric-Bernstam, F., Albain, K. S., Hayes, D. F., Lin, N. U., Perez, E. A., Goldstein, L. J., Chia, S. K. L., Dhesy-Thind, S., Rastogi, P., Alba-Conejo, E., Delaloge, S., Martín, M., Kelly, C. M., Ruíz-Borrego, M., Gil-Gil, M., Arce-Salinas, C. H., … Hortobágyi, G. N. (2021). 21-gene assay to inform chemotherapy benefit in node-positive breast cancer. New England Journal of Medicine, 385(25), 2336–2347. Scopus. https://doi.org/10.1056/NEJMoa2108873
Marabelle, A., Fakih, M., Lopez, J., Shah, M., Shapira-Frommer, R., Nakagawa, K., Chung, H. C., Kindler, H. L., López-Martín, J. A., Miller, W. H., Italiano, A., Kao, S., Piha-Paul, S. A., Delord, J.-P., McWilliams, R. R., Fabrizio, D. A., Aurora-Garg, D., Xu, L., Jin, F., … Bang, Y.-J. (2020). Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: Prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. The Lancet Oncology, 21(10), 1353–1365. Scopus. https://doi.org/10.1016/S1470-2045(20)30445-9
Mukhlis, L. (2025a). A Phenomenological Study of Personal Spiritual Experiences in Navigating Religious Pluralism within Interfaith Communities. Irfana: Journal of Religious Studies, 1(6), 212–220.
Mukhlis, L. (2025b). Spiritual Grounds for Economic Growth: A Qualitative Exploration of Rural Indonesian Women’s Transformative Journeys Through Mosque-Led Empowerment Programs. Servina: Jurnal Pengabdian Kepada Masyarakat, 1(8), 289–298.
Mukhlis, L., & Abdullah, M. N. (2025). Hukum Keluarga Islam di Indonesia (1st ed.). Mukhlisina Revolution Center.
Mukhlis, L., Arifin, T., Ridwan, A. H., & Zulbaidah. (2024). Integrating Artificial Intelligenceand Maqāṣid al-Syarī‘ah: Revolutionizing Indonesia’s Sharia Online Trading System. Computer Fraud and Security, 2024(11), 301–309. https://doi.org/10.52710/cfs.238
Mukhlis, L., Arifin, T., Ridwan, A. H., & Zulbaidah. (2025). Reorientation of Sharia Stock Regulations: Integrating Taṣarrufāt al-Rasūl and Maqāṣid al-Sharī‘ah for Justice and Sustainability. Journal of Information Systems Engineering and Management, 10(10s), 58–66. https://doi.org/10.52783/jisem.v10i10s.1341
Mukhlis, L., Arifin, T., Ridwan, A. H., Zulbaidah, Rosadi, A., & Solehudin, E. (2025). Reformulation of Islamic Stock Law: The Application of Taṣarrufāt al-Rasūl and Maqāṣid al-Syarī‘ahto Develop a Dynamic and Sustainable Islamic Capital Market in Indonesia. Journal of Posthumanism, 5(3), 1–13. https://doi.org/10.63332/joph.v5i3.913
Mukhlis, L., Janwari, Y., & Syafe`i, R. (2023). INDONESIA STOCK EXCHANGE: THEORETICAL AND PHILOSOPHICAL ANALYSIS OF MUDHARABAH AND MUSYARAKAH CONTRACTS. Yurisprudentia: Jurnal Hukum Ekonomi, 9(2), 243–264. https://doi.org/10.24952/yurisprudentia.v9i2.8466
Mukhlis, L., Maryam, S., & Sormin, S. A. (2023). Model Pembelajaran Living History Berbasis PjBL Untuk Meningkatkan Keterampilan Histografi Mahasiswa. Jurnal Educatio FKIP UNMA, 9(4), 1800–1809. https://doi.org/10.31949/educatio.v9i4.5595
Mukhlis, L., & Saidah, Y. (2025). Dynamics of Nature-Based learning in Developing Children’s Motoricic Skills: Teacher and Parent Perspectives. HUMANISMA: Journal of Gender Studies, 9(1), 64–79. http://dx.doi.org/10.30983/humanisme.v4i2.9366
Mukhlis, L., Suradi, Janwari, Y., & Syafe`i, R. (2023). Sosialisasi Saham Syariah sebagai Instrumen Pengembangan Ekonomi Masyarakat di Badan Kontak Majelis Taklim (BKMT) Kabupaten Mandailing Natal. Jurnal Pengabdian Multidisiplin, 3(2), 2–9. https://doi.org/10.51214/japamul.v3i2.604
Ommen, S. R., Mital, S., Burke, M. A., Day, S. M., Deswal, A., Elliott, P., Evanovich, L. L., Hung, J., Joglar, J. A., Kantor, P., Kimmelstiel, C., Kittleson, M., Link, M. S., Maron, M. S., Martinez, M. W., Miyake, C. Y., Schaff, H. V., Semsarian, C., & Sorajja, P. (2020). 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology, 76(25), e159–e240. Scopus. https://doi.org/10.1016/j.jacc.2020.08.045
Park, K., Haura, E. B., Leighl, N. B., Mitchell, P., Shu, C. A., Girard, N., Viteri, S., Han, J.-Y., Kim, S.-W., Lee, C. K., Sabari, J. K., Spira, A. I., Yang, T.-Y., Kim, D.-W., Lee, K. H., Sanborn, R. E., Trigo, J., Goto, K., Lee, J.-S., … Cho, B. C. (2021). Amivantamab in egfr exon 20 insertion- mutated non-small-cell lung cancer progressing on platinum chemotherapy: Initial results from the chrysalis phase i study. Journal of Clinical Oncology, 39(30), 3391–3402. Scopus. https://doi.org/10.1200/JCO.21.00662
Pawlotsky, J.-M., Negro, F., Aghemo, A., Berenguer, M., Dalgard, O., Dusheiko, G., Marra, F., Puoti, M., & Wedemeyer, H. (2020). EASL recommendations on treatment of hepatitis C: Final update of the series☆. Journal of Hepatology, 73(5), 1170–1218. Scopus. https://doi.org/10.1016/j.jhep.2020.08.018
Raal, F. J., Rosenson, R. S., Reeskamp, L. F., Hovingh, G. K., Kastelein, J., Rubba, P., Ali, S., Pharm, D., Banerjee, P., Chan, K.-C., Gipe, D. A., Khilla, N., Pordy, R., Weinreich, D. M., Yancopoulos, G. D., Zhang, Y., & Gaudet, D. (2020). Evinacumab for Homozygous Familial Hypercholesterolemia. New England Journal of Medicine, 383(8), 711–720. Scopus. https://doi.org/10.1056/NEJMoa2004215
Reardon, D. A., Brandes, A. A., Omuro, A., Mulholland, P., Lim, M., Wick, A., Baehring, J., Ahluwalia, M. S., Roth, P., Bähr, O., Phuphanich, S., Sepúlveda, J. M., De Souza, P., Sahebjam, S., Carleton, M., Tatsuoka, K., Taitt, C., Zwirtes, R., Sampson, J., & Weller, M. (2020). Effect of Nivolumab vs Bevacizumab in Patients with Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncology, 6(7), 1003–1010. Scopus. https://doi.org/10.1001/jamaoncol.2020.1024
Subbiah, V., Lassen, U., Élez, E., Italiano, A., Curigliano, G., Javle, M., de Braud, F., Prager, G. W., Greil, R., Stein, A., Fasolo, A., Schellens, J. H. M., Wen, P. Y., Viele, K., Boran, A. D., Gasal, E., Burgess, P., Ilankumaran, P., & Wainberg, Z. A. (2020). Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): A phase 2, open-label, single-arm, multicentre basket trial. The Lancet Oncology, 21(9), 1234–1243. Scopus. https://doi.org/10.1016/S1470-2045(20)30321-1
Turner, N. C., Oliveira, M., Howell, S. J., Dalenc, F., Corteś, J., Gomez, H. L., Hu, X., Jhaveri, K., Krivorotko, P., Loibl, S., Morales Murillo, S., Okera, M., Park, Y. H., Sohn, J., Toi, M., Tokunaga, E., Yousef, S., Zhukova, L., de Bruin, E. C., … Rugo, H. S. (2023). Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. New England Journal of Medicine, 388(22), 2058–2070. Scopus. https://doi.org/10.1056/NEJMoa2214131
Tutt, A. N. J., Garber, J. E., Kaufman, B., Viale, G., Fumagalli, D., Rastogi, P., Gelber, R. D., de Azambuja, E., Fielding, A., Balmaña, J., Domchek, S. M., Gelmon, K. A., Hollingsworth, S. J., Korde, L. A., Linderholm, B., Bandos, H., Senkus, E., Suga, J. M., Zhimin Shao, Z., … Geyer, C. E. (2021). Adjuvant olaparib for patients with BRCA1- Or BRCA2-mutated breast cancer. New England Journal of Medicine, 384(25), 2394–2405. Scopus. https://doi.org/10.1056/NEJMoa2105215
Weller, M., Van Den Bent, M., Preusser, M., Le Rhun, E., Tonn, J. C., Minniti, G., Bendszus, M., Balana, C., Chinot, O., Dirven, L., French, P., Hegi, M. E., Jakola, A. S., Platten, M., Roth, P., Rudá, R., Short, S., Smits, M., Taphoorn, M. J. B., … Wick, W. (2021). EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nature Reviews Clinical Oncology, 18(3), 170–186. Scopus. https://doi.org/10.1038/s41571-020-00447-z
Wolf, J., Seto, T., Han, J.-Y., Reguart, N., Garon, E. B., Groen, H. J. M., Tan, D. S. W., Hida, T., de Jonge, M., Orlov, S. V., Smit, E. F., Souquet, P.-J., Vansteenkiste, J., Hochmair, M., Felip, E., Nishio, M., Thomas, M., Ohashi, K., Toyozawa, R., … Heist, R. S. (2020). Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. New England Journal of Medicine, 383(10), 944–957. Scopus. https://doi.org/10.1056/NEJMoa2002787
Wright, G. W., Huang, D. W., Phelan, J. D., Coulibaly, Z. A., Roulland, S., Young, R. M., Wang, J. Q., Schmitz, R., Morin, R. D., Tang, J., Jiang, A., Bagaev, A., Plotnikova, O., Kotlov, N., Johnson, C. A., Wilson, W. H., Scott, D. W., & Staudt, L. M. (2020). A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications. Cancer Cell, 37(4), 551-568.e14. Scopus. https://doi.org/10.1016/j.ccell.2020.03.015
Zuberi, S. M., Wirrell, E., Yozawitz, E., Wilmshurst, J. M., Specchio, N., Riney, K., Pressler, R., Auvin, S., Samia, P., Hirsch, E., Galicchio, S., Triki, C., Carter Snead, O. C., Wiebe, S., Cross, J. H., Tinuper, P., Scheffer, I. E., Perucca, E., Moshé, S. L., & Nabbout, R. (2022). ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia, 63(6), 1349–1397. Scopus. https://doi.org/10.1111/epi.17239