{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:49:44Z","timestamp":1785797384312,"version":"3.56.0"},"reference-count":28,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T00:00:00Z","timestamp":1687651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Proving clinical superiority of personalized care models in interventional and surgical pain management is challenging. The apparent difficulties may arise from the inability to standardize complex surgical procedures that often involve multiple steps. Ensuring the surgery is performed the same way every time is nearly impossible. Confounding factors, such as the variability of the patient population and selection bias regarding comorbidities and anatomical variations are also difficult to control for. Small sample sizes in study groups comparing iterations of a surgical protocol may amplify bias. It is essentially impossible to conceal the surgical treatment from the surgeon and the operating team. Restrictive inclusion and exclusion criteria may distort the study population to no longer reflect patients seen in daily practice. Hindsight bias is introduced by the inability to effectively blind patient group allocation, which affects clinical result interpretation, particularly if the outcome is already known to the investigators when the outcome analysis is performed (often a long time after the intervention). Randomization is equally problematic, as many patients want to avoid being randomly assigned to a study group, particularly if they perceive their surgeon to be unsure of which treatment will likely render the best clinical outcome for them. Ethical concerns may also exist if the study involves additional and unnecessary risks. Lastly, surgical trials are costly, especially if the tested interventions are complex and require long-term follow-up to assess their benefit. Traditional clinical testing of personalized surgical pain management treatments may be more challenging because individualized solutions tailored to each patient\u2019s pain generator can vary extensively. However, high-grade evidence is needed to prompt a protocol change and break with traditional image-based criteria for treatment. In this article, the authors review issues in surgical trials and offer practical solutions.<\/jats:p>","DOI":"10.3390\/jpm13071044","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T01:42:32Z","timestamp":1687743752000},"page":"1044","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Randomized Clinical Trials and Observational Tribulations: Providing Clinical Evidence for Personalized Surgical Pain Management Care Models"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5224-4977","authenticated-orcid":false,"given":"Ivo","family":"Abraham","sequence":"first","affiliation":[{"name":"Pharmacy Medicine, and Clinical Translational Sciences, University of Arizona, Roy P. Drachman Hall, Rm. B306H, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7842-2914","authenticated-orcid":false,"given":"Kai-Uwe","family":"Lewandrowski","sequence":"additional","affiliation":[{"name":"Center for Advanced Spine Care of Southern Arizona, Tucson, AZ 85712, USA"},{"name":"Department of Orthopaedics, Fundaci\u00f3n Universitaria Sanitas, Bogot\u00e1 111321, Colombia"},{"name":"Department of Orthopedics, Hospital Universit\u00e1rio Gaffre e Guinle, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro 20270-004, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Elfar","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, College of Medicine\u2014Tucson Campus, Health Sciences Innovation Building (HSIB), University of Arizona, 1501 N. Campbell Avenue, Tower 4, 8th Floor, Suite 8401, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zong-Ming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, College of Medicine\u2014Tucson Campus, Health Sciences Innovation Building (HSIB), University of Arizona, 1501 N. Campbell Avenue, Tower 4, 8th Floor, Suite 8401, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5236-0903","authenticated-orcid":false,"given":"Rossano Kepler Alvim","family":"Fiorelli","sequence":"additional","affiliation":[{"name":"Department of General and Specialized Surgery, Gaffr\u00e9e e Guinle University Hospital, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 20270-004, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio G.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Brasilia, Federal District, Brasilia 70919-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan P.","family":"Lorio","sequence":"additional","affiliation":[{"name":"Advanced Orthopaedics, 499 E. Central Pkwy, Ste. 130, Altamonte Springs, FL 32701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt W.","family":"Burkhardt","sequence":"additional","affiliation":[{"name":"Wirbels\u00e4ulenzentrum\/Spine Center\u2014WSC, Hirslanden Klinik Zurich, Witellikerstrasse 40, 8032 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim M.","family":"Oertel","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Neurochirurgie, Universit\u00e4t des Saarlandes, Kirrberger Stra\u00dfe 100, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Charite Universitaetsmedizin Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Yang","sequence":"additional","affiliation":[{"name":"Orthopaedic Department, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge Felipe Ram\u00edrez","family":"Le\u00f3n","sequence":"additional","affiliation":[{"name":"Minimally Invasive Spine Center Bogot\u00e1 D.C. Colombia, Reina Sof\u00eda Clinic Bogot\u00e1 D.C. Colombia, Department of Orthopaedics, Fundaci\u00f3n Universitaria Sanitas, Bogot\u00e1 110141, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert E.","family":"Telfeian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Dowling","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14071-550, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roth A. A.","family":"Vargas","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Foundation Hospital Centro M\u00e9dico Campinas, Campinas 13083-210, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Ramina","sequence":"additional","affiliation":[{"name":"Neurological Institute of Curitiba, Curitiba 80230-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Asefi","sequence":"additional","affiliation":[{"name":"Department of Biology, Nano-Biology, University of North Carolina, Greensboro, NC 27413, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo S\u00e9rgio Teixeira","family":"de Carvalho","sequence":"additional","affiliation":[{"name":"Pain and Spine Minimally Invasive Surgery Service, Gaffre e Guinle University Hospital, Rio de Janeiro 20270-004, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helton","family":"Defino","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14071-550, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Moyano","sequence":"additional","affiliation":[{"name":"La Sociedad Iberolatinoamericana De Columna (SILACO), the Spine Committee of the Ecuadorian Society of Orthopaedics and Traumatology (Comit\u00e9 de Columna de la Sociedad Ecuatoriana de Ortopedia y Traumatolog\u00eda), Quito 170521, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3686-8907","authenticated-orcid":false,"given":"Nicola","family":"Montemurro","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Azienda Ospedaliero Universitaria Pisana, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Yeung","sequence":"additional","affiliation":[{"name":"Desert Institute for Spine Care, Phoenix, AZ 85020, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Novellino","sequence":"additional","affiliation":[{"name":"Guinle and State Institute of Diabetes and Endocrinology, Rio de Janeiro 20270-004, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of Teams\/Organizations\/Institutions","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"657","DOI":"10.7326\/0003-4819-134-8-200104170-00011","article-title":"The CONSORT Statement: Revised Recommendations for Improving the Quality of Reports of Parallel-Group Randomized Trials","volume":"134","author":"Moher","year":"2001","journal-title":"Ann. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.jmig.2020.10.011","article-title":"Re-evaluating \u201cSuccess\u201d as It Pertains to Surgical Trials","volume":"28","author":"Naumann","year":"2021","journal-title":"J. Minim. Invasive Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1526-4637.2009.00770.x","article-title":"Proof or consequences: Who shall pay for the evidence in pain medicine?","volume":"11","author":"Bogduk","year":"2010","journal-title":"Pain Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e020629","DOI":"10.1136\/bmjopen-2017-020629","article-title":"Patient-reported outcome measurements in clinical routine of trauma, spine and craniomaxillofacial surgeons: Between expectations and reality: A survey among 1212 surgeons","volume":"8","author":"Joeris","year":"2018","journal-title":"BMJ Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1097\/BRS.0000000000003050","article-title":"The Association Between Patient Reported Outcomes of Spinal Surgery and Societal Costs: A Register Based Study","volume":"44","author":"Jonsson","year":"2019","journal-title":"Spine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"E4","DOI":"10.3171\/2019.2.FOCUS18618","article-title":"Objective functional assessment using the \u201cTimed Up and Go\u201d test in patients with lumbar spinal stenosis","volume":"46","author":"Stienen","year":"2019","journal-title":"Neurosurg. Focus"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1001\/jama.1995.03520290060030","article-title":"Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials","volume":"273","author":"Schulz","year":"1995","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"ii46","DOI":"10.1136\/qhc.12.suppl_2.ii46","article-title":"Hindsight bias, outcome knowledge and adaptive learning","volume":"12","author":"Henriksen","year":"2003","journal-title":"Qual. Saf. Health Care"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/SLA.0b013e3181cf863d","article-title":"Randomized Controlled Trials of Surgical Interventions","volume":"251","author":"Farrokhyar","year":"2010","journal-title":"Ann. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/bjs.4418","article-title":"Trials in surgery","volume":"91","author":"Lilford","year":"2004","journal-title":"Br. J. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00423-013-1155-5","article-title":"Insights into surgical trials: Methodological challenges and solutions","volume":"399","author":"Bruckner","year":"2014","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1097\/SLA.0000000000002965","article-title":"Toward a Consensus on Centralization in Surgery","volume":"268","author":"Vonlanthen","year":"2018","journal-title":"Ann. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1007\/s002689900649","article-title":"Issues in surgical randomized controlled trials","volume":"23","author":"McLeod","year":"1999","journal-title":"World J. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jmig.2006.12.006","article-title":"Is a placebo-controlled surgical trial an oxymoron?","volume":"14","author":"Boyle","year":"2007","journal-title":"J. Minim. Invasive Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1002\/1097-0142(19941101)74:9+<2666::AID-CNCR2820741814>3.0.CO;2-P","article-title":"Barriers to clinical trials: Part II: Knowledge and attitudes of potential participants","volume":"74","author":"Schain","year":"1994","journal-title":"Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Foster, J.M., Sawyer, S.M., Smith, L., Reddel, H.K., and Usherwood, T. (2015). Barriers and facilitators to patient recruitment to a cluster randomized controlled trial in primary care: Lessons for future trials. BMC Med. Res. Methodol., 15.","DOI":"10.1186\/s12874-015-0012-3"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1076-7460.2004.01709.x","article-title":"Willingness to participate in cardiac trials","volume":"13","author":"Peterson","year":"2004","journal-title":"Am. J. Geriatr. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Barcot, O., Boric, M., Dosenovic, S., Cavar, M., Kadic, A.J., Pericic, T.P., Vukicevic, I., Vuka, I., and Puljak, L. (2020). Adequacy of risk of bias assessment in surgical vs non-surgical trials in Cochrane reviews: A methodological study. BMC Med. Res. Methodol., 20.","DOI":"10.1186\/s12874-020-01123-7"},{"key":"ref_19","unstructured":"von Elm, E., Altman, D.G., Egger, M., Pocock, S.J., Gotzsche, P.C., and Vandenbroucke, J.P. (2023, June 10). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies. Available online: https:\/\/www.equator-network.org\/reporting-guidelines\/strobe\/."},{"key":"ref_20","first-page":"S39","article-title":"Breaking Through the \u201cGlass Ceiling\u201d of Minimally Invasive Spine Surgery","volume":"41","author":"Phillips","year":"2016","journal-title":"Spine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s00701-019-03850-3","article-title":"Randomized controlled trials in surgery and the glass ceiling effect","volume":"161","author":"Solheim","year":"2019","journal-title":"Acta Neurochir."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.rccot.2022.10.003","article-title":"Breaking through the glass ceiling effect of high-grade clinical evidence creation in orthopaedics & trauma","volume":"36","author":"Lewandrowski","year":"2022","journal-title":"Rev. Colomb. Ortop. Traumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1002\/sim.1903","article-title":"Stratification and weighting via the propensity score in estimation of causal treatment effects: A comparative study","volume":"23","author":"Lunceford","year":"2004","journal-title":"Stat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1002\/sim.2328","article-title":"A comparison of propensity score methods: A case-study estimating the effectiveness of post-AMI statin use","volume":"25","author":"Austin","year":"2006","journal-title":"Stat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1001\/jamasurg.2021.5614","article-title":"Data-Driven Individualized Surgical Decision-making: Beyond \u201cBetter on Average\u201d Clinical Trial Results","volume":"157","author":"Mori","year":"2022","journal-title":"JAMA Surg."},{"key":"ref_26","first-page":"Mr000031","article-title":"Comparison of protocols and registry entries to published reports for randomised controlled trials","volume":"2011","author":"Dwan","year":"2011","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_27","first-page":"3s72","article-title":"Methodology for the assessment of new targeted treatments in clinical trials. Future perspectives","volume":"60","author":"Quoix","year":"2004","journal-title":"Rev. Pneumol. Clin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.3233\/JRS-150675","article-title":"Patients in need of medicine information","volume":"27","author":"Kazaryan","year":"2015","journal-title":"Int. J. Risk Saf. Med."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/7\/1044\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:00:36Z","timestamp":1760126436000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/7\/1044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,25]]},"references-count":28,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["jpm13071044"],"URL":"https:\/\/doi.org\/10.3390\/jpm13071044","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,25]]}}}