Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (799 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Clinical Protocol; Protocol, Clinical; Protocols, Clinical; Treatment Protocols; Protocols, Treatment; Treatment Protocol; Clinical Research Protocol; Protocol, Clinical Research.
Where it fits in the MeSH classification
- Broader topics
- Therapeutics; Epidemiologic Study Characteristics
- Narrower topics
- Antineoplastic Protocols; Standing Orders; Clinical Trial Protocols as Topic
- See also
- Clinical Trials as Topic; Patient Care Planning; Practice Guidelines as Topic; Patient Selection; Critical Pathways
Research landscape
PubMed indexes 209,949 records tagged with the MeSH heading “Clinical Protocols” (counts retrieved 2026-10-29). 42,096 of them (20.1%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 71,930 records.
Reviews account for 32,048 records (15.3%) and meta-analyses for 3,165. Randomized controlled trials number 21,123 (10.1%) as a share of all records on the topic. Randomized trials make up a comparatively large share of this literature, which means many treatment questions have been tested directly.
Show the data
| Period | Records |
|---|---|
| through 1999 | 46,544 |
| 2000-2009 | 49,379 |
| 2010-2019 | 71,930 |
| 2020 onward | 42,096 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 32,048 | 15.3% |
| Meta-analyses | 3,165 | 1.5% |
| Randomized controlled trials | 21,123 | 10.1% |
Method: PubMed query "Clinical Protocols"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in clinical research
Research methods determine how much a result can be trusted. Randomized trials guard against confounding, systematic reviews and meta-analyses combine many studies, and observational designs are valuable but can show only association. Reporting standards, trial registration and pre-specified outcomes reduce bias. When reading about a method, ask what problem it is designed to solve and which problems it does not solve.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Trials in progress: CARMAN - study protocol of a randomized controlled, international, multicenter, open-label phase II trial evaluating early treatment intensification in patients with high-risk mantle cell lymphoma using CAR-T-cell treatment after an abbreviated induction therapy with rituximab and ibrutinib and 6 months ibrutinib maintenance as compared to standard of care induction and maintenance [1]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundBrexucabtagene-autoleucel (brexu-cel) is an anti-CD19 chimeric antigen receptor T-cell (CAR-T) product approved for relapsed/refractory Mantle Cell Lymphoma (MCL) after two prior treatment lines, including Bruton tyrosine kinase inhibitors (BTKi).
- Closing excerpt
- Trial registrationEU clinical trial number: 2022-502405-15-00.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (355 words)
BackgroundBrexucabtagene-autoleucel (brexu-cel) is an anti-CD19 chimeric antigen receptor T-cell (CAR-T) product approved for relapsed/refractory Mantle Cell Lymphoma (MCL) after two prior treatment lines, including Bruton tyrosine kinase inhibitors (BTKi). Patients with high-risk (hr) disease-defined by high-intermediate or high-risk MIPI-c, p53 overexpression, or TP53 alterations-have a poor prognosis, underscoring the need for improved first-line strategies. The European Mantle Cell Lymphoma Network therefore designed a phase II trial to investigate the incorporation of brexu-cel into first-line therapy for hr MCL.MethodsCARMAN is a randomized controlled, international, multicenter, open-label phase II trial evaluating efficacy, safety, and tolerability of an abbreviated induction followed by first-line brexu-cel and 6 months Ibrutinib maintenance (Arm A) as compared to standard of care induction and maintenance (Arm B). In Arm A, induction consists of two cycles of ibrutinib plus rituximab (I + R) followed by two cycles of R-CHOP plus ibrutinib (I). R-CHOP + I may be omitted in patients achieving complete or partial remission after two cycles of I + R, who then receive one additional I + R cycle before brexu-cel infusion and I maintenance. Arm B comprises a TRIANGLE-like regimen based on age, fitness, and investigator choice (alternating R-CHOP plus ibrutinib/R-DHAP or IR-bendamustine), followed by IR maintenance. Overall, 150 patients from five European countries are randomized 1:1. The primary endpoint is failure-free survival from randomization, with failure event defined as the earliest of stable disease at the end of induction (Arm B, or Arm A if brexu-cel is not infused) or within 12 weeks from CAR-T-cell infusion (Arm A), disease progression after induction, or death from any cause. Secondary endpoints include efficacy (overall and complete response rates and PET-negative CR rate 6 months from randomization as assessed according to Lugano criteria, molecular remission rate as measured by MRD), safety and tolerability (adverse events graded according to CTCAE), and patient-reported quality of life as measured by the EORTC-QLQ-C30 and EORTC-QLQ-NHL-HG29 questionnaires.DiscussionWhen complete, CARMAN will provide important information on efficacy and safety in first-line CAR-T cell therapy in hr MCL and has the potential to prepare a practice changing confirmatory trial for these difficult-to-treat patients. Recruitment is ongoing.Trial registrationEU clinical trial number: 2022-502405-15-00.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42581349 · DOI · PMC13459421
Optimizing venetoclax duration with hypomethylating agents for newly diagnosed acute myeloid leukemia: impact on response and survival [2]
Abstract reading summary — source excerpts
- Opening excerpt
- The addition of venetoclax to hypomethylating agents (HMAs) is standard for older adults with newly diagnosed acute myeloid leukemia (AML).
- Closing excerpt
- These findings support further prospective evaluation of reduced VEN durations in this population.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (229 words)
The addition of venetoclax to hypomethylating agents (HMAs) is standard for older adults with newly diagnosed acute myeloid leukemia (AML). However, prolonged venetoclax (VEN) exposure can cause cytopenias and infections, raising questions about optimal duration. We conducted a single‑center retrospective study of 102 patients treated between 2018 and 2025 with azacitidine or decitabine plus VEN administered for 14 (n = 22), 21 (n = 48), or 28 (n = 32) days per 28‑day cycle. Baseline cytogenetic and molecular profiling, responses by 2022/2024 ELN criteria, measurable residual disease (MRD), cumulative incidence of relapse (CIR), disease‑free survival (DFS), and overall survival (OS) were analyzed using competing‑risks regression and Cox models. Median age was 68 years and patients received a median of 4 cycles. Composite remission (CR/CRi/CRh/MLFS) was 66.7%, with MRD negativity in 75.0% of responders. Remission and MRD negativity rates did not differ significantly across VEN‑duration cohorts. Median OS and DFS were 17.3 and 12.3 months, respectively, with no significant differences in OS, DFS, and CIR between 14‑, 21‑, and 28‑day cohorts. Grade ≥ 3 cytopenias and transfusion independence rates also did not differ significantly. In this cohort, shortening VEN exposure to 14 or 21 days did not show a significant difference in response, survival, relapse risk, and toxicity profiles relative to a 28‑day schedule in our cohort. These findings support further prospective evaluation of reduced VEN durations in this population.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42734838 · DOI · PMC13574922
Atezolizumab in early triple-negative breast cancer: the randomized phase 3 NSABP B-59/GeparDouze trial [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Triple-negative breast cancer (TNBC) is an aggressive subtype with an activated tumor immune microenvironment.
- Closing excerpt
- gov registration: NCT03281954 .
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (215 words)
Triple-negative breast cancer (TNBC) is an aggressive subtype with an activated tumor immune microenvironment. The multicenter, multinational, double-blinded NSABP B-59/GeparDouze trial evaluated the addition of atezolizumab (atezo) (773 patients randomized) or placebo (777 patients) to sequential taxane-carboplatin-anthracycline-based neoadjuvant chemotherapy in stage II-III TNBC. The addition of atezo did not significantly improve the primary endpoint of event-free survival (EFS) (HR, 0.80 (95% CI, 0.062-1.03); stratified log-rank P = 0.083, 4-year EFS rates difference 3.3%). The HR for overall survival was 0.86 (95% CI, 0.62-1.19), with a 4-year benefit of 0.7%. Prespecified subgroup analyses suggested heterogeneity in EFS, with benefit of atezo in patients presenting with clinical lymph node involvement (Pinteraction = 0.039). Treatment-emergent adverse events with grades ≥3 were reported in 75.3% (atezo) versus 73.4% (placebo), and immune-related adverse events were reported in 27.6% (atezo) versus 11.4% (placebo). A total of 196 (25.5%) patients discontinued atezo and 143 (18.8%) patients discontinued placebo in the neoadjuvant phase. In an exploratory mRNA-based subset analysis, patients with basal-like immune-activated tumors may have benefited from atezo. TNBC subtyping to identify basal-like immune-activated tumors and quantification of tumor-infiltrating lymphocytes to identify tumors with high tumor-infiltrating lymphocyte counts could be a promising strategy to identify patients who benefit from the addition of immune checkpoint inhibitors to neoadjuvant chemotherapy. ClinicalTrials.gov registration: NCT03281954 .
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42680950 · DOI · PMC13668648
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Neoadjuvant Immune Checkpoint Inhibitors Plus Chemotherapy in Early Breast Cancer: A Systematic Review and Meta-Analysis [4]
- Research article Comparison of first-line chemotherapy regimens in unresectable locally advanced or metastatic pancreatic cancer: a systematic review and Bayesian network meta-analysis [5]
- Research article Analysis of multi-drug cancer nanomedicine [6]
- Research article The safety and efficacy of neoadjuvant PD-1 inhibitor plus chemotherapy for patients with locally advanced gastric cancer: a systematic review and meta-analysis [7]
- Research article Quadruplet regimens for patients with newly diagnosed multiple myeloma: a systematic review and meta-analysis [8]
- Research article Chemotherapy and radiotherapy for advanced pancreatic cancer [9]
References
- Tilch MK, Schmidt C, Trneny M, Giné E, Hermine O, Ohler A, et al.. Trials in progress: CARMAN - study protocol of a randomized controlled, international, multicenter, open-label phase II trial evaluating early treatment intensification in patients with high-risk mantle cell lymphoma using CAR-T-cell treatment after an abbreviated induction therapy with rituximab and ibrutinib and 6 months ibrutinib maintenance as compared to standard of care induction and maintenance. . 2026. PMID 42581349 · DOI · PMC13459421
- Ginosyan AA, Ashouri K, Cheng J, Ford L, Baya M, Humayun L, et al.. Optimizing venetoclax duration with hypomethylating agents for newly diagnosed acute myeloid leukemia: impact on response and survival. . 2026. PMID 42734838 · DOI · PMC13574922
- Loibl S, Tang G, Nekljudova V, Rastogi P, Rachakonda S, Reinisch M, et al.. Atezolizumab in early triple-negative breast cancer: the randomized phase 3 NSABP B-59/GeparDouze trial. . 2026. PMID 42680950 · DOI · PMC13668648
- Villacampa G, Navarro V, Matikas A, Ribeiro JM, Schettini F, Tolosa P, et al.. Neoadjuvant Immune Checkpoint Inhibitors Plus Chemotherapy in Early Breast Cancer: A Systematic Review and Meta-Analysis. JAMA Oncol. 2024. PMID 39207778 · DOI · PMC12422158
- Mastrantoni L, Chiaravalli M, Spring A, Beccia V, Di Bello A, Bagalà C, et al.. Comparison of first-line chemotherapy regimens in unresectable locally advanced or metastatic pancreatic cancer: a systematic review and Bayesian network meta-analysis. Lancet Oncol. 2024. PMID 39542008 · DOI
- Benderski K, Lammers T, Sofias AM. Analysis of multi-drug cancer nanomedicine. Nat Nanotechnol. 2025. PMID 40374796 · DOI · PMC12373501
- Yu Z, Liang C, Xu Q, Yuan Z, Chen M, Li R, et al.. The safety and efficacy of neoadjuvant PD-1 inhibitor plus chemotherapy for patients with locally advanced gastric cancer: a systematic review and meta-analysis. Int J Surg. 2025. PMID 39172720 · DOI · PMC11745722
- Ebraheem MS, Chakraborty R, Rochwerg B, Visram A, Mohyuddin GR, Venner CP, et al.. Quadruplet regimens for patients with newly diagnosed multiple myeloma: a systematic review and meta-analysis. Blood Adv. 2024. PMID 39348665 · DOI · PMC11629212
- Haggstrom L, Chan WY, Nagrial A, Chantrill LA, Sim HW, Yip D, et al.. Chemotherapy and radiotherapy for advanced pancreatic cancer. Cochrane Database Syst Rev. 2024. PMID 39635901 · DOI · PMC11619003
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.