SPIRIT extension and elaboration for n-of-1 trials: SPENT 2019 checklist
Open accessAbstract
Randomised clinical trials are the preferred method for establishing average intervention effects for groups. Using key methodological elements of these trials, n-of-1 trials provide rigorous evidence of intervention effects for individuals. N-of-1 trials are particularly useful for situations where randomised clinical trials are not always feasible or appropriate, such as for individuals with rare diseases, comorbid conditions, or using concurrent treatments. N-of-1 trials enhance precision when intervention effects are heterogeneous between individuals. Here, we describe an extension to the SPIRIT (standard protocol items: recommendations for interventional trials) guideline, SPENT (SPIRIT extension for n-of-1 trials), to improve the completeness and transparency of n-of-1 trial protocols. SPENT is also aligned with the CONSORT (consolidated standards of reporting trials) extension for n-of-1 trials (CENT). The guideline development group followed the development strategy for reporting guidelines endorsed by the EQUATOR Network. SPENT began with a systematic review for n-of-1 protocol recommendations. After analysis to identify possible SPENT items, a three round Delphi process was implemented, with international participation involving researchers, patient advocates, and other stakeholders. This was followed by in-person meetings and email discussion of the SPENT group to achieve consensus. SPENT has 14 extension items specific to n-of-1 trials, a checklist for n-of-1 trial protocol abstracts, and additional guidance for eight SPIRIT items where trialists could encounter issues specific to n-of-1 trials. This paper describes the rationale and development process, and provides examples and explanations for each SPENT checklist item.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The present protocol follows the SPENT checklist (SPIRIT extension for N-of-1 trials).
“The present protocol follows the SPENT checklist (SPIRIT extension for N-of-1 trials; Porcino et al., 2020) that can be consulted in Supplementary material A (SPENT checklist) and B (abstract checklist).”
From Unified Protocol for the transdiagnostic treatment of emotional disorders in people with post COVID-19 condition: study protocol for a multiple baseline n-of-1 trial (2023) · cites this paper as Porcino et al., 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials
the CONSORT Group, Schulz, K. F., Altman, D. G., & Moher, D. (2010) · BMC Medicine · doi:10.1186/1741-7015-8-18 · Cited by 13,371 · see citing works
Hoffmann, T. C., Glasziou, P. P., Boutron, I., Milne, R., Perera, R., Moher, D., Altman, D. G., Barbour, V., Macdonald, H., Johnston, M., et al. (2014) · BMJ · doi:10.1136/bmj.g1687 · Cited by 10,548 · see citing works
SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials
Chan, A.-W., Tetzlaff, J. M., Altman, D. G., Laupacis, A., Gøtzsche, P. C., Krleža-Jerić, K., Hróbjartsson, A., Mann, H., Dickersin, K., Berlin, J. A., et al. (2013) · Annals of Internal Medicine · doi:10.7326/0003-4819-158-3-201302050-00583 · Cited by 7,363 · see citing works
SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials
Chan, A.-W., Tetzlaff, J. M., Gotzsche, P. C., Altman, D. G., Mann, H., Berlin, J. A., Dickersin, K., Hrobjartsson, A., Schulz, K. F., Parulekar, W. R., et al. (2013) · BMJ · doi:10.1136/bmj.e7586 · Cited by 6,251 · see citing works
Users' guides to the medical literature
Guyatt, G. H. (1993) · JAMA · doi:10.1001/jama.270.17.2096 · Cited by 2,970 · see citing works
External validity of randomised controlled trials: “To whom do the results of this trial apply?”
Rothwell, P. M. (2005) · The Lancet · doi:10.1016/s0140-6736(04)17670-8 · Cited by 2,544 · see citing works
Meta-analysis of individual participant data: rationale, conduct, and reporting
Riley, R. D., Lambert, P. C., & Abo-Zaid, G. (2010) · BMJ · doi:10.1136/bmj.c221 · Cited by 1,701 · see citing works
Boutron, I., Altman, D. G., Moher, D., Schulz, K. F., Ravaud, P., & for the CONSORT NPT Group* (2017) · Annals of Internal Medicine · doi:10.7326/m17-0046 · Cited by 1,538 · see citing works
Guidance for Developers of Health Research Reporting Guidelines
Moher, D., Schulz, K. F., Simera, I., & Altman, D. G. (2010) · PLoS Medicine · doi:10.1371/journal.pmed.1000217 · Cited by 1,437 · see citing works
Personalized medicine: Time for one-person trials
Schork, N. J. (2015) · Nature · doi:10.1038/520609a · Cited by 1,235 · see citing works
Personalized medicine: motivation, challenges, and progress
Goetz, L. H., & Schork, N. J. (2018) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.05.006 · Cited by 976 · see citing works
Cross-Over Trials in Clinical Research
Senn, S. J. (1994) · Technometrics · doi:10.1080/00401706.1994.10485798 · Cited by 777 · see citing works
Delphi methodology in health research: how to do it?
Trevelyan, E., & Robinson, N. (2015) · European Journal of Integrative Medicine · doi:10.1016/j.eujim.2015.07.002 · Cited by 747 · see citing works
Cross‐over Trials In Clinical Research
Senn, S. (2002) · doi:10.1002/0470854596 · Cited by 653 · see citing works
Paterson, C. (1996) · BMJ · doi:10.1136/bmj.312.7037.1016 · Cited by 451 · see citing works
Patient involvement in clinical research: why, when, and how
Sacristán, J. A., Aguarón, A., Avendaño, C., Garrido, P., Carrion, J., Gutierrez, A., Kroes, R. A., & Flores, A. (2016) · Patient Preference and Adherence · doi:10.2147/ppa.s104259 · Cited by 363 · see citing works
Multiplicity in randomised trials II: subgroup and interim analyses
Schulz, K. F., & Grimes, D. A. (2005) · The Lancet · doi:10.1016/s0140-6736(05)66516-6 · Cited by 357 · see citing works
The Ethics of Placebo-Controlled Trials — A Middle Ground
Emanuel, E. J., & Miller, F. G. (2001) · New England Journal of Medicine · doi:10.1056/nejm200109203451211 · Cited by 354 · see citing works
A clinician's guide for conducting randomized trials in individual patients.
Guyatt, G. H., Sackett, D. L., Adachi, J. D., Roberts, R. E., Chong, J. P., Rosenbloom, D., & Keller, J. (1988) · Europe PMC (PubMed Central) · Cited by 275 · see citing works
CONSORT extension for reporting N-of-1 trials (CENT) 2015 Statement
Vohra, S., Shamseer, L., Sampson, M., Bukutu, C., Schmid, C. H., Tate, R. L., Nikles, J., Zucker, D. R., Kravitz, R. L., Guyatt, G. H., et al. (2015) · BMJ · doi:10.1136/bmj.h1738 · Cited by 239 · see citing works
Duan, N., Kravitz, R. L., & Schmid, C. H. (2013) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2013.04.006 · Cited by 239 · see citing works
Zucker, D. R., Ruthazer, R., & Schmid, C. H. (2010) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2010.04.020 · Cited by 184 · see citing works
Considerations for the Systematic Analysis and Use of Single-Case Research
Horner, R. H., Swaminathan, H., Sugai, G. M., & Smolkowski, K. (2012) · Education and Treatment of Children · doi:10.1353/etc.2012.0011 · Cited by 172 · see citing works
Clarke, M. J., Hopewell, S., & Chalmers, I. (2010) · The Lancet · doi:10.1016/s0140-6736(10)61045-8 · Cited by 166 · see citing works
Run-in Periods in Randomized Trials
Pablos-Méndez, A., Barr, R. G., & Shea, S. (1998) · JAMA · doi:10.1001/jama.279.3.222 · Cited by 163 · see citing works
Price, A. I., Schroter, S., Snow, R., Hicks, M. D., Harmston, R., Staniszewska, S. H., Parker, S., & Richards, T. (2018) · BMJ Open · doi:10.1136/bmjopen-2017-020452 · Cited by 155 · see citing works
CONSORT extension for reporting N-of-1 trials (CENT) 2015: Explanation and elaboration
Shamseer, L., Sampson, M., Bukutu, C., Schmid, C. H., Nikles, J., Tate, R. L., Johnston, B. C., Zucker, D. R., Shadish, W. R., Kravitz, R. L., et al. (2015) · BMJ · doi:10.1136/bmj.h1793 · Cited by 154 · see citing works
The history and development of N-of-1 trials
Mirza, R. D., Punja, S., Vohra, S., & Guyatt, G. H. (2017) · Journal of the Royal Society of Medicine · doi:10.1177/0141076817721131 · Cited by 145 · see citing works
CONSORT extension for reporting N-of-1 trials (CENT) 2015: explanation and elaboration
Shamseer, L., Sampson, M., Bukutu, C., Schmid, C. H., Nikles, J., Tate, R. L., Johnston, B. C., Zucker, D. R., Shadish, W. R., Kravitz, R. L., et al. (2015) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2015.05.018 · Cited by 142 · see citing works
Maggin, D. M., Swaminathan, H., Rogers, H. J., O’Keeffe, B. V., Sugai, G. M., & Horner, R. H. (2011) · Journal of School Psychology · doi:10.1016/j.jsp.2011.03.004 · Cited by 138 · see citing works
Maggin, D. M., O’Keeffe, B. V., & Johnson, A. H. (2011) · Exceptionality · doi:10.1080/09362835.2011.565725 · Cited by 120 · see citing works
Tate, R. L., Perdices, M., McDonald, S., Togher, L., & Rosenkoetter, U. (2014) · Neuropsychological Rehabilitation · doi:10.1080/09602011.2013.875043 · Cited by 100 · see citing works
Using n-of-1 trials as a clinical tool to improve prescribing.
Nikles, J., Clavarino, A. M., & Mar, C. D. (2005) · PubMed · Cited by 90 · see citing works
Users' Guides to the Medical Literature
Fineout‐Overholt, E. (2002) · Evidence-Based Nursing · doi:10.1136/ebn.5.1.8 · Cited by 87 · see citing works
Patient-Centeredness in the Design of Clinical Trials
Mullins, C. D., Vandigo, J. E., Zheng, Z., & Wicks, P. J. (2014) · Value in Health · doi:10.1016/j.jval.2014.02.012 · Cited by 85 · see citing works
Guidelines for randomized clinical trial protocol content: a systematic review
Tetzlaff, J., Chan, A., Kitchen, J., Sampson, M., Tricco, A. C., & Moher, D. (2012) · Systematic Reviews · doi:10.1186/2046-4053-1-43 · Cited by 80 · see citing works
Sample size considerations for n -of-1 trials
Senn, S. J. (2017) · Statistical Methods in Medical Research · doi:10.1177/0962280217726801 · Cited by 71 · see citing works
N-of-1 trials are a tapestry of heterogeneity
Punja, S., Bukutu, C., Shamseer, L., Sampson, M., Hartling, L., Urichuk, L., & Vohra, S. (2016) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2016.03.023 · Cited by 63 · see citing works
N of 1 trials in diabetes: making individual therapeutic decisions
Τσάπας, Α., & Matthews, D. R. (2008) · Diabetologia · doi:10.1007/s00125-008-0983-2 · Cited by 52 · see citing works
Barr, C., Marois, M., Sim, I., Schmid, C. H., Wilsey, B. L., Ward, D., Duan, N., Hays, R. D., Selsky, J., Servadio, J. L., et al. (2015) · Trials · doi:10.1186/s13063-015-0590-8 · Cited by 46 · see citing works
Baek, E., Moeyaert, M., Petit-Bois, M., Beretvas, S. N., den Noortgate, W. V., & Ferron, J. (2014) · Neuropsychological Rehabilitation · doi:10.1080/09602011.2013.835740 · Cited by 44 · see citing works
Is It Always Unethical to Use a Placebo in a Clinical Trial?
Stang, A., Hense, H. W., Jöckel, K., Turner, E. H., & Tramèr, M. R. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020072 · Cited by 41 · see citing works
Hierarchical Linear Modeling Meta-Analysis of Single-Subject Design Research
Gage, N. A., & Lewis, T. J. (2012) · The Journal of Special Education · doi:10.1177/0022466912443894 · Cited by 36 · see citing works
What is Right and What is Wrong About Evidence‐Based Medicine?
Julian, D. G. (2003) · Journal of Cardiovascular Electrophysiology · doi:10.1046/j.1540-8167.14.s9.18.x · Cited by 22 · see citing works
Senior, H., Mitchell, G. K., Nikles, J., Carmont, S.-A. S., Schlüter, P. J., Currow, D. C., Vora, R., Yelland, M. J., Agar, M. R., Good, P. D., et al. (2013) · BMC Palliative Care · doi:10.1186/1472-684x-12-17 · Cited by 19 · see citing works
Guidelines for Patient-Reported Outcomes in Clinical Trial Protocols
Mehran, R., Baber, U., & Dangas, G. (2018) · JAMA · doi:10.1001/jama.2017.21541 · Cited by 19 · see citing works
Brookes, S. T., Biddle, L., Paterson, C., Woolhead, G., & Dieppe, P. A. (2007) · Trials · doi:10.1186/1745-6215-8-10 · Cited by 18 · see citing works
Crossover design and its application in late‐phase diabetes studies
Wang, T., Malone, J. K., Fu, H., Heilmann, C. R., Qu, Y., & Huster, W. J. (2016) · Journal of Diabetes · doi:10.1111/1753-0407.12412 · Cited by 16 · see citing works
Berger, V. W., & Vali, B. (2011) · Journal of Biopharmaceutical Statistics · doi:10.1080/10543406.2011.550107 · Cited by 14 · see citing works
Vrinten, C., Lipka, A. F., van Zwet, E. W., Schimmel, K. J. M., Cornel, M. C., Kuijpers, M. R., Hekster, Y. A., Weinreich, S. S., & Verschuuren, J. J. G. M. (2015) · BMJ Open · doi:10.1136/bmjopen-2015-007863 · Cited by 14 · see citing works
Using N-of-1 Trials in Evidence-Based Clinical Practice
Τσάπας, Α. (2009) · JAMA · doi:10.1001/jama.2009.276 · Cited by 14 · see citing works
Punja, S., Nikles, J., Senior, H., Mitchell, G. K., Schmid, C. H., Heussler, H., Witmans, M., & Vohra, S. (2016) · Trials · doi:10.1186/s13063-016-1499-6 · Cited by 11 · see citing works
Nikles, J., Mitchell, G. K., Hardy, J. R., Agar, M. R., Senior, H., Carmont, S.-A. S., Schlüter, P. J., Good, P. D., Vora, R., & Currow, D. C. (2013) · BMC Palliative Care · doi:10.1186/1472-684x-12-39 · Cited by 10 · see citing works
Alemayehu, C. M., Mitchell, G. K., Aseffa, A., Clavarino, A. M., McGree, J. M., & Nikles, J. (2017) · Trials · doi:10.1186/s13063-017-2212-0 · Cited by 10 · see citing works
Porcino, A., Punja, S., Chan, A., Kravitz, R. L., Orkin, A. M., Ravaud, P., Schmid, C. H., & Vohra, S. (2017) · Systematic Reviews · doi:10.1186/s13643-017-0525-4 · Cited by 9 · see citing works
Senior, H., McKinlay, L., Nikles, J., Schlüter, P. J., Carmont, S.-A. S., Waugh, M.-C. A., Epps, A., Lloyd, O., & Mitchell, G. K. (2013) · BMC Pediatrics · doi:10.1186/1471-2431-13-89 · Cited by 8 · see citing works
Flagged first, then by citations
1 of the 57 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Schmid CH, Duan MSPHN. DEcIDE Methods Centre N-of-1 Guidance Panel. Chapter 4: Statistical design and analytic considerations for n-of-1 trials. In: Kravitz RL, Duan MSPHN, eds. Design and implementation of N-of-1 trials: a user's guide. Agency for Healthcare Research and Quality, 2014:33-53.
- Punja S, Eslick I, Duan MSPHN, Vohra S. DEcIDE Methods Centre N-of- 1 Guidance Panel. Chapter 2: An ethical framework for n-of-1 trials: clinical care, quality improvement, or human subjects research? In: Kravitz RL, Duan MSPHN, eds. Design and implementation of n-of-1 trials: a user's guide. Agency for Healthcare Research and Quality, 2014:13-22.
Cited by
Sorted by citations
SPIRIT 2025 statement: updated guideline for protocols of randomised trials
Chan, A.-W., Boutron, I., Hopewell, S., Moher, D., Schulz, K. F., Collins, G. S., Tunn, R., Aggarwal, R., Berkwits, M., Berlin, J. A., et al. (2025) · BMJ · doi:10.1136/bmj-2024-081477 · Cited by 460 · see citing works
SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials
Hróbjartsson, A., Boutron, I., Hopewell, S., Moher, D., Schulz, K. F., Collins, G. S., Tunn, R., Aggarwal, R., Berkwits, M., Berlin, J. A., et al. (2025) · BMJ · doi:10.1136/bmj-2024-081660 · Cited by 171 · see citing works
SPIRIT 2025 statement: updated guideline for protocols of randomized trials
Chan, A., Boutron, I., Hopewell, S., Moher, D., Schulz, K. F., Collins, P. G. S., Tunn, R., Aggarwal, R., Berkwits, M., Berlin, J. A., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03668-w · Cited by 143 · see citing works
SPIRIT 2025 statement: updated guideline for protocols of randomised trials
Chan, A., Boutron, I., Hopewell, S., Moher, D., Schulz, K. F., Collins, P. G. S., Tunn, R., Aggarwal, R., Berkwits, M., Berlin, J. A., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(25)00770-6 · Cited by 111 · see citing works
Chan, A., Boutron, I., Hopewell, S., Moher, D., Schulz, K. F., Collins, P. G. S., Tunn, R., Aggarwal, R., Berkwits, M., Berlin, J. A., et al. (2025) · JAMA · doi:10.1001/jama.2025.4486 · Cited by 108 · see citing works
SPIRIT 2025 statement: Updated guideline for protocols of randomised trials
Chan, A., Boutron, I., Hopewell, S., Moher, D., Schulz, K. F., Collins, P. G. S., Tunn, R., Aggarwal, R., Berkwits, M., Berlin, J. A., et al. (2025) · PLoS Medicine · doi:10.1371/journal.pmed.1004589 · Cited by 77 · see citing works
Systematic Review of N-of-1 Studies in Rare Genetic Neurodevelopmental Disorders
Müller, A. R., Brands, M. M. M. G., van de Ven, P. M., Roes, K. C. B., Cornel, M. C., van Karnebeek, C., Wijburg, F. A., Daams, J. G., Boot, E., & van Eeghen, A. M. (2021) · Neurology · doi:10.1212/wnl.0000000000011597 · Cited by 65 · see citing works
van der Spoel, E., Roelfsema, F., & van Heemst, D. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.619568 · Cited by 62 · see citing works
A Priori Justification for Effect Measures in Single-Case Experimental Designs
Manolov, R., Moeyaert, M., & Fingerhut, J. E. (2022) · Perspectives on Behavior Science · doi:10.1007/s40614-021-00282-2 · Cited by 53 · see citing works
So near yet so far: why won’t the UK prescribe medical cannabis?
Nutt, D., Bazire, S., Phillips, L. D., & Schlag, A. K. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-038687 · Cited by 51 · see citing works
The SPIRIT Checklist—lessons from the experience of SPIRIT protocol editors
Qureshı, R., Gough, A., & Loudon, K. (2022) · Trials · doi:10.1186/s13063-022-06316-7 · Cited by 43 · see citing works
Individualized therapy trials: navigating patient care, research goals and ethics
Kane, P. B., Bittlinger, M., & Kimmelman, J. (2021) · Nature Medicine · doi:10.1038/s41591-021-01519-y · Cited by 44 · see citing works
Methods used to develop the SPIRIT 2024 and CONSORT 2024 Statements
Tunn, R., Boutron, I., Chan, A., Collins, P. G. S., Hróbjartsson, A., Moher, D., Schulz, K. F., de Beyer, J. A., Nejstgaard, C. H., Østengaard, L., et al. (2024) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2024.111309 · Cited by 41 · see citing works
Lam, J., Svensson, P., & Alstergren, P. (2020) · Journal of Medical Internet Research · doi:10.2196/22326 · Cited by 33 · see citing works
Kendall, T. J., Robinson, M., Brierley, D. J., Lim, S. J., O’Connor, D. J., Shaaban, A. M., Lewis, I., Chan, A., & Harrison, D. J. (2021) · The Lancet Oncology · doi:10.1016/s1470-2045(21)00344-2 · Cited by 30 · see citing works
Yap, C., Rekowski, J., Ursino, M., Solovyeva, O., Patel, D., Dimairo, M., Weir, C. J., Chan, A., Jaki, T., Mander, A., et al. (2023) · BMJ · doi:10.1136/bmj-2023-076386 · Cited by 27 · see citing works
Müller, M. P., Metelmann, C., Thies, K., Greif, R. T., Scquizzato, T., Deakin, C. D., Auricchio, A., Barry, T., Berglund, E., Böttiger, B. W., et al. (2023) · Resuscitation · doi:10.1016/j.resuscitation.2023.110087 · Cited by 26 · see citing works
StudyU: A Platform for Designing and Conducting Innovative Digital N-of-1 Trials
Konigorski, S., Wernicke, S., Slosarek, T., Zenner, A. M., Strelow, N., Ruether, D. F., Henschel, F., Manaswini, M., Pottbäcker, F., Edelman, J. A., et al. (2022) · Journal of Medical Internet Research · doi:10.2196/35884 · Cited by 25 · see citing works
Evidence for effect of l-serine, a novel therapy for GRIN2B-related neurodevelopmental disorder
den Hollander, B., Veenvliet, A. R. J., Rothuizen-Lindenschot, M., van Essen, P., Peters, G., Santos‐Gómez, A., Olivella, M., Altafaj, X., Brands, M. M. M. G., Jacobs, B., et al. (2023) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2023.107523 · Cited by 16 · see citing works
Gkouskou, K. K., Grammatikopoulou, M. G., Lazou, E., Sanoudou, D., Goulis, D. G., & Eliopoulos, A. G. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.772243 · Cited by 15 · see citing works
Daalen, J. M. J., Meinders, M. J., Giardina, F., Roes, K. C. B., Stunnenberg, B. C., Mathur, S., Ainslie, P. N., Thijssen, D. H. J., & Bloem, B. R. (2022) · BMC Neurology · doi:10.1186/s12883-022-02770-7 · Cited by 14 · see citing works
Simons, R., Koordeman, R., de Looff, P. C., & Otten, R. (2021) · JMIR Research Protocols · doi:10.2196/24911 · Cited by 12 · see citing works
Müller, A. R., Zinkstok, J., Rommelse, N. N. J., van de Ven, P. M., Roes, K. C. B., Wijburg, F. A., Rooij‐Askes, E. S. P. D., Linders, C. C., Boot, E., & van Eeghen, A. M. (2021) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-021-02003-z · Cited by 12 · see citing works
Tanious, R., & Manolov, R. (2022) · Neuropsychological Rehabilitation · doi:10.1080/09602011.2022.2035774 · Cited by 12 · see citing works
Müller, A. R., den Hollander, B., van de Ven, P. M., Roes, K. C. B., Geertjens, L., Bruining, H., van Karnebeek, C., Jansen, F. E., de Wit, M. Y., ten Hoopen, L. W., et al. (2024) · BMC Psychiatry · doi:10.1186/s12888-023-05422-3 · Cited by 12 · see citing works
A proposal for the assessment of replication of effects in single‐case experimental designs
Manolov, R., Tanious, R., & Fernández‐Castilla, B. (2022) · Journal of Applied Behavior Analysis · doi:10.1002/jaba.923 · Cited by 11 · see citing works
Kahan, B. C., Juszczak, E., Beller, E., Birchenall, M., Chan, A., Hall, S. S., Little, P. S., Fletcher, J., Golub, R. M., Goulão, B., et al. (2025) · BMJ · doi:10.1136/bmj-2024-080785 · Cited by 10 · see citing works
Scherpbier, I. C. A., Abrahamse, M. E., Belleman, R. G., Popma, A., & Lindauer, R. (2022) · JMIR Research Protocols · doi:10.2196/34120 · Cited by 9 · see citing works
The Value of Case Reports for Graduate Medical Education
Lowenfels, A. B., Mamtani, R., Solomon, L., Maisonneuve, P., & Cheema, S. (2022) · Journal of Graduate Medical Education · doi:10.4300/jgme-d-21-01115.1 · Cited by 9 · see citing works
Chatters, R., Hawksworth, O., Julious, S. A., & Cook, A. (2024) · Trials · doi:10.1186/s13063-024-08261-z · Cited by 8 · see citing works
Bresnahan, R., Copley, S., Eldabe, S. S., Thomson, S., North, R. B., Baranidharan, G., Levy, R. M., Collins, P. G. S., Taylor, R. S., & Duarte, R. V. (2024) · EClinicalMedicine · doi:10.1016/j.eclinm.2024.102933 · Cited by 8 · see citing works
Wilmont, I., Loeffen, M., & Hoogeboom, T. J. (2024) · International Journal of Qualitative Studies on Health and Well-Being · doi:10.1080/17482631.2024.2318810 · Cited by 7 · see citing works
Evidence and reporting standards in N-of-1 medical studies: a systematic review
Batley, P. N., McClure, E. B., Brewer, B. N., Contractor, A. A., Batley, N. J., Hedges, L. V., & Chin, S. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02562-8 · Cited by 8 · see citing works
Managing abnormal liver tests in children with inflammatory bowel disease
van Rheenen, P. F. (2021) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000001045 · Cited by 7 · see citing works
Rochat, L., & Manolov, R. (2024) · Journal of Behavioral and Cognitive Therapy · doi:10.1016/j.jbct.2024.100502 · Cited by 9 · see citing works
Personalized (N-of-1) Clinical Trials for Inflammatory Bowel Disease: Opportunities and Challenges
Honap, S., Zou, G., Danese, S., Peyrin‐Biroulet, L., & Jairath, V. (2024) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2024.08.028 · Cited by 6 · see citing works
Nazari, G., Diep, D., & MacDermid, J. C. (2021) · Osteoarthritis and Cartilage Open · doi:10.1016/j.ocarto.2021.100215 · Cited by 6 · see citing works
Protocol of the CONSORT and SPIRIT Extension for multicenter clinical trials
Zhang, X., Dong, C., Wang, N., Chan, C., Lau, C. T., Wang, J., Miao, J., Yao, C., Li, Y., Lü, A., et al. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1241152 · Cited by 6 · see citing works
den Hollander, B., Rothuizen-Lindenschot, M., Geertjens, L., Vaz, F. M., Brands, M. M. M. G., Le, H. L., van Eeghen, A. M., van de Ven, P. M., Cornel, M. C., Jacobs, B., et al. (2023) · Contemporary Clinical Trials Communications · doi:10.1016/j.conctc.2023.101233 · Cited by 6 · see citing works
N-of-1 Trials in Rare Genetic Neurodevelopmental Disorders
Hartman, A. L. (2021) · Neurology · doi:10.1212/wnl.0000000000011603 · Cited by 6 · see citing works
Multilevel Model Selection Applied to Single-Case Experimental Design Data
Manolov, R., & Moeyaert, M. (2025) · Journal of Behavioral Education · doi:10.1007/s10864-025-09593-9 · Cited by 5 · see citing works
Analyzing data in single-case experimental designs: Objectives and available software options
Manolov, R., & Rochat, L. (2024) · Journal of Behavioral and Cognitive Therapy · doi:10.1016/j.jbct.2024.100511 · Cited by 5 · see citing works
Yang, M. H., Sun, R., Wang, Y., Xu, H., Zou, B.-H., Yang, Y., Cong, M., Zheng, Y., Yu, L., Ma, F., et al. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.587627 · Cited by 4 · see citing works
Lindstad, M. Ø., Obstfelder, A. U., Sveen, U., & Stigen, L. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-060206 · Cited by 5 · see citing works
Manolov, R., & Onghena, P. (2023) · Behavior Research Methods · doi:10.3758/s13428-023-02230-1 · Cited by 5 · see citing works
McDonald, S., Tan, S. X., Banu, S., van Driel, M., McGree, J. M., Mitchell, G. K., & Nikles, J. (2021) · Patient · doi:10.1007/s40271-021-00540-0 · Cited by 4 · see citing works
Clinical Trial Registries, Results Databases, and Research Data Repositories
Krleža-Jerić, K., Mahmić-Kaknjo, M., & Emam, K. E. (2023) · Health informatics · doi:10.1007/978-3-031-27173-1_17 · Cited by 3 · see citing works
Blueprint for clinical N-of-1 strategies with off-label precision treatments in monogenic epilepsies
Defelippe, V. M., Brilstra, E. H., Otte, W. M., van Thiel, G. J. M. W., Cross, J. H., O'Callaghan, F. J., GIORGIS, V. D., Perucca, E., Braun, K. P. J., & Jansen, F. E. (2025) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-025-03750-z · Cited by 3 · see citing works
Nilsson, S., Wiljén, A., Bergquist, J., Chaplin, J. E., Johnson, E., Karlsson, K., Lindroth, T., Schwarz, A., Stenmarker, M., Thunberg, G., et al. (2021) · BMJ Open · doi:10.1136/bmjopen-2020-042726 · Cited by 3 · see citing works
Complete reporting of clinical trials requires more than journal articles
Mayo‐Wilson, E. (2025) · BMJ · doi:10.1136/bmj.r494 · Cited by 3 · see citing works
N-of-1 Trials, Their Reporting Guidelines, and the Advancement of Open Science Principles
Porcino, A., & Vohra, S. (2022) · Harvard Data Science Review · doi:10.1162/99608f92.a65a257a · Cited by 3 · see citing works
Zarbin, M. A., & Novack, G. D. (2021) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2021.0059 · Cited by 3 · see citing works
Wang, P., Foo, N., Su, C., Leung, N. Y. T., Song, S. W., Seres, G., Sapanel, Y., Hooi, L., Wong, A., Ong, Y. H., et al. (2026) · medRxiv · doi:10.64898/2026.02.10.26345969 · Cited by 3 · see citing works
Hall, S. S., Juszczak, E., Birchenall, M., Elbourne, D. R., Beller, E., Chan, A., Little, P. S., Montgomery, A. A., & Kahan, B. C. (2025) · BMJ Open · doi:10.1136/bmjopen-2023-082917 · Cited by 2 · see citing works
de Carvalho, M. C. L., Simões, M. D. M. D., Adler, U., Viana, A. B., de Sousa, C. N. S., & Sanders, L. L. O. (2025) · British Journal of Clinical Pharmacology · doi:10.1002/bcp.70382 · Cited by 4 · see citing works
Hall, S. S., Shoesmith, E., Riga, E., Mills, D. S., Gibsone, S., McMillan, D., Wu, Q., Clarke, C., & Ratschen, E. (2026) · BMC Medical Research Methodology · doi:10.1186/s12874-026-02848-7 · Cited by 2 · see citing works
Madieu, E., Thérriault, P.-Y., Cantin, N., & Baghdadli, A. (2023) · BMJ Open · doi:10.1136/bmjopen-2023-073854 · Cited by 2 · see citing works
EQUATOR Network Mapping Review for Dysphagia Research
Steele, C. M., Burdick, R. J., Dallal-York, J., Shapira‐Galitz, Y., & Abrams, S. W. (2024) · American Journal of Speech-Language Pathology · doi:10.1044/2023_ajslp-23-00306 · Cited by 2 · see citing works
Perillat, L. O. M., McFadyen, A., Furlong, P., & Anderson, J. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1493832 · Cited by 2 · see citing works
Dutra, L. R. D. V., Silva‐Filho, E., Oliveira, M., Tavares, B. N. P., Pegado, R., & Micussi, M. T. A. B. C. (2021) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2021.05.038 · Cited by 2 · see citing works
Editorial: Creating Evidence From Real World Patient Digital Data
Nikles, J., Daza, E. J., McDonald, S., Hekler, E. B., & Schork, N. J. (2021) · Frontiers in Computer Science · doi:10.3389/fcomp.2020.636996 · Cited by 2 · see citing works
Martínez-Borba, V., Martínez-García, L., Peris-Baquero, Ó., Osma, J., & del Corral-Beamonte, E. (2023) · Frontiers in Psychology · doi:10.3389/fpsyg.2023.1160692 · Cited by 1 · see citing works
The ‘power of 1’: The ethics and epistemology of ‘N-of-1 trials’ in oncology
Heynemann, S., Lipworth, W. L., McLachlan, S., Philip, J. A. M., John, T., & Kerridge, I. (2025) · Research Ethics · doi:10.1177/17470161251351401 · Cited by 1 · see citing works
Should we compromise on n-of-1 data analyses?
Batley, P. N. (2024) · BJPsych Advances · doi:10.1192/bja.2023.65 · Cited by 1 · see citing works
del Álamo, M., Zafirova, B., Esdaile, M., Karam, S., Kläger, S., & Kubiak, C. (2025) · Rare Disease and Orphan Drugs Journal · doi:10.20517/rdodj.2024.49 · Cited by 1 · see citing works
Luo, W., & Li, C. (2026) · Research Square · doi:10.21203/rs.3.rs-9237753/v1 · Cited by 1 · see citing works
Perdue, W. L., Reus, V. I., & Yeamans, R. (2020) · medRxiv · doi:10.1101/2020.10.25.20212282
Expanded Access and Compassionate Use in Alzheimer’s Disease Drug Development
Kerwin, D. R. (2022) · Cambridge University Press eBooks · doi:10.1017/9781108975759.027
Kaput, J., Monteiro, J. P., Morine, M. J., & Kussmann, M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-824010-6.00003-4
The reporting quality of N‐of‐1 trials and protocols still needs improvement
Wei, Z., Chu, X., Han, J., Zhang, N., Li, Y., Yang, C., Wang, Q., Li, J., Belal, A. A., Yan, P., et al. (2022) · Journal of Evidence-Based Medicine · doi:10.1111/jebm.12484
Perdue, W. L., Reus, V. I., van Breemen, R. B., Muchiri, R. N., & Yeamans, R. (2022) · medRxiv · doi:10.1101/2022.08.09.22278588
Chatters, R., Hawksworth, L., Julious, S. A., & Cook, A. (2023) · Research Square · doi:10.21203/rs.3.rs-3120458/v1
Ghosh, S., Siddique, M., Chatterjee, K., Pal, R. K., Alam, S. M., Halder, I., Chandra, S., Midya, A., & Saha, S. (2025) · Homeopathy · doi:10.1055/a-2547-9741
Daalen, J. M. J., Meinders, M. J., Giardina, F., Roes, K. C. B., Stunnenberg, B. C., Mathur, S., Ainslie, P. N., Thijssen, D. H. J., & Bloem, B. R. (2022) · Figshare · doi:10.6084/m9.figshare.20315866
Daalen, J. M. J., Meinders, M. J., Giardina, F., Roes, K. C. B., Stunnenberg, B. C., Mathur, S., Ainslie, P. N., Thijssen, D. H. J., & Bloem, B. R. (2022) · Figshare · doi:10.6084/m9.figshare.20315863
de Lange, J., Telman, L. G. E., van den Heuvel, M. W. H., Vroegindeweij, A., & Bodden, D. H. M. (2026) · BMC Psychology · doi:10.1186/s40359-026-04252-8
An n ‐of‐1 gene‐directed drug repurposing trial for an ultrarare genetic condition
Jha, V., Tsetsos, C., Bedford, M., Costain, G., Vohra, S., Martinez, J. P. D., Héon, E., Vorstman, J. A. S., Gorodetsky, C., Vincent, A., et al. (2026) · Epilepsia · doi:10.1002/epi.70253
South, A., Taheri, S., Asamoah, G. D., & Morris, T. P. (2026) · Research Methods in Medicine & Health Sciences · doi:10.1177/26320843261459862
Hernandez-Garcia, E., Edkins, A., Chrysikou, E. G., Ordóñez-Mena, J. M., Nekhlyudov, L., Kim, J. B., McLean, G. R., Frost, H., & Panigrahy, D. (2026) · BMJ Open · doi:10.1136/bmjopen-2025-111748
- Authors
- Porcino, A. J., Shamseer, L., Chan, A.-W., Kravitz, R. L., Orkin, A., Punja, S., Ravaud, P., Schmid, C. H., & Vohra, S.
- Affiliations
- BC Cancer Agency (CA)
- Ottawa Hospital Research Institute (CA)
- University of Toronto (CA)
- University of California Davis Medical Center (US)
- University of Alberta (CA)
- Sorbonne Paris Cité (FR)
- Brown University (US)
- Corresponding author
- Vohra, Sunita
- ORCID
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2020-02-27
- Volume
- 368
- Pages
- m122
- ISSN
- 1756-1833 (ISSN-L)
- OpenAlex
- W3007287716
- Cited by
- 81
- References
- 57
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 11 · 2023: 11 · 2022: 16 · 2021: 16 · 2020: 4
- FWCI
- 7.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
- Locations
- BMJ (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Sociology and Political Science › Delphi Technique in Research
- Keywords
- N-of-1 trials, reporting guidelines, protocol transparency, rare diseases, patient involvement in guideline development
- MeSH terms
- Clinical Protocols, Consensus Statements as Topic, Consensus Development Conferences as Topic, Humans, Research Design, Randomized Controlled Trials as Topic, Guidelines as Topic, Clinical Trials Data Monitoring Committees, Checklist
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
