A systematic review protocol is the document that proves your review was planned before you started. It records your research question, your eligibility criteria, your search strategy, and your synthesis plan before any searching or screening begins. Without a registered protocol, a reviewer has no way to know whether your outcomes were selected after seeing the results, whether your eligibility criteria shifted to include or exclude troublesome studies, or whether your planned analysis changed to produce a cleaner answer. These possibilities are not hypothetical. They are the documented sources of reporting bias that protocols exist to prevent.
The registration figures make the stakes concrete. A study of PROSPERO records found that only 53.6 percent of registered systematic reviews were eventually published (Runjic et al., Journal of Clinical Epidemiology, 2019). Nearly half of registered reviews never reach a journal. Researchers who write a strong, detailed protocol before they begin are the ones most likely to complete the review, because a well-written protocol is a project plan as much as a methodological document. For research teams who need support writing a systematic review protocol that meets PROSPERO submission requirements and Cochrane standards, ScribeLab Writer's systematic review writing service covers protocol development from the research question through to the full PROSPERO submission.
Quick Answer:
A systematic review protocol must be registered on PROSPERO before the search begins. PROSPERO accepts systematic reviews, rapid reviews, and other review types with a direct health-related outcome. It does not accept scoping reviews, narrative reviews, or mapping reviews. Use OSF for those. The protocol must specify the research question in PICO format, the databases to be searched, the eligibility criteria for studies, the screening and data extraction process, the risk-of-bias tool for each study design, and the planned synthesis approach. Registration gives you a citable DOI immediately, which you reference in your methods section. The most common reason protocols are returned for amendment is vague eligibility criteria. Register before you run a single database search.
Why Register a Protocol Before You Search
Protocol registration serves three purposes that affect both the scientific credibility of your review and its chance of publication.
It prevents outcome reporting bias. When researchers register their primary and secondary outcomes before the analysis, they cannot quietly drop outcomes that showed no effect or elevate secondary outcomes that looked favorable. Outcome reporting bias is one of the five GRADE domains for downgrading certainty of evidence, and a reviewer who suspects it will downgrade your evidence base.
It establishes priority. If another team is working on the same review question, registration establishes that your work was underway first. PROSPERO's new duplicate-topic detection feature, introduced with the 2025 platform relaunch, actively flags registrations that closely match existing records and notifies both teams.
It creates a public audit trail. Your registration record documents what you planned. Any deviation from the plan must be disclosed in the final manuscript. Transparency about protocol deviations is now an explicit PRISMA 2020 reporting requirement.
Booth and colleagues described PROSPERO's function in the foundational "nuts and bolts" paper as establishing the a priori nature of the systematic review. that the methods were decided before the evidence was examined (Booth et al., Systematic Reviews, 2012;1:2). This a priori status is what separates a systematic review from a narrative summary of whatever literature the authors found useful.
What PROSPERO Accepts and What It Does Not
PROSPERO, maintained by the Centre for Reviews and Dissemination (CRD) at the University of York, accepts systematic reviews with a direct health-related outcome. The register reached 306,444 published records as of 11 December 2024, with approximately 6,458 new records published in November 2024 alone (Centre for Reviews and Dissemination, University of York, 2025).
PROSPERO accepts:
Systematic reviews of interventions
Systematic reviews of diagnostic test accuracy
Systematic reviews of prognosis
Systematic reviews of prevalence or incidence
Systematic reviews of etiology or risk factors
Rapid reviews
PROSPERO does not accept:
Scoping reviews
Narrative literature reviews
Mapping reviews
Qualitative evidence syntheses (unless conducted as part of a mixed-methods systematic review with a health outcome)
For scoping reviews, use the Open Science Framework (OSF) at osf.io. OSF registration is instant, provides a DOI immediately, is version-controlled so amendments are tracked automatically, and accepts all review types, including scoping reviews, qualitative syntheses, and non-health reviews. A guide to writing a scoping review and registering its protocol on OSF is available in the scoping review methodology guide.
Table 1: PROSPERO vs OSF: Which Register to Use
Feature | PROSPERO | OSF (Open Science Framework) |
|---|---|---|
Accepts | Systematic reviews, rapid reviews, and other review types with a direct health-related outcome. Interventions, diagnostic accuracy, prognosis, prevalence, etiology. | All review types, including scoping reviews, qualitative evidence syntheses, narrative reviews, mapping reviews, and non-health reviews. |
Does not accept | Scoping reviews, narrative literature reviews, mapping reviews. Reviews without a direct health-related outcome. | No restrictions on review type or topic area. |
Processing | Reviewed by CRD staff. May be returned for revision if out of scope or if key fields are insufficiently detailed. 2025 relaunch added automated duplicate-topic detection. | Instant registration. No staff review. Self-managed with full version history automatically tracked. |
DOI | Assigned immediately upon submission. Citable before CRD review is complete. Visible to other researchers. | Assigned immediately upon registration. Citable at once. |
Amendments | Formal amendment request submitted to CRD. Reviewed and published as a dated amendment to the existing record. | Edits create new versions automatically. Full version history visible to anyone. No formal review required. |
Cost | Free. | Free for most uses. Storage-based paid tiers available for large file deposits. |
URL | crd.york.ac.uk/prospero | osf.io |
What a Systematic Review Protocol Must Contain
A protocol document contains more than the PROSPERO registration fields. The PROSPERO record is a summary. The full protocol is the complete methodological plan. Many journals and Cochrane require the full protocol as a supplementary file at submission.
Background and rationale. A brief review of what is already known on the topic, with evidence of the gap the review addresses. Cite existing systematic reviews and explain why a new review is needed. because the evidence base has grown substantially, because existing reviews have methodological limitations, or because no review has addressed this specific population or outcome.
Research question in PICO format: The question must be specific enough that two independent reviewers would agree on whether any given study meets the criteria. Vague questions like "What are the effects of exercise on health?" are the most common reason PROSPERO returns a registration for revision.
Eligibility criteria: types of studies. Specify which study designs you will include. If you include both RCTs and non-randomized studies of interventions, name both and explain which appraisal tools you will use for each.
Eligibility criteria: types of participants. Specify age range, diagnosis or condition, clinical setting, and any relevant co-morbidity or risk factors. Be precise: "adults with type 2 diabetes" is more defensible than "patients with diabetes."
Eligibility criteria: types of interventions. Specify the intervention including dose, duration, and delivery mode where relevant. If any variant of the intervention is excluded, state why.
Eligibility criteria: types of outcomes. List primary outcomes first, then secondary outcomes. Name the specific measurement tools or scales where the evidence base uses multiple instruments. Outcomes listed in the protocol but not reported in the final manuscript are a GRADE downgrading concern and a PRISMA 2020 compliance issue.
Search strategy: Include the full Boolean search string for at least one database as a supplementary file. State all databases, the date range, the date the search was run, and all limiters applied. State whether you will search grey literature sources and name them.
Screening process: State how many reviewers will screen titles and abstracts, and how many will assess full texts. State whether a pilot screening exercise will be conducted. State the software tool.
Data extraction plan: State who will extract data, whether the extraction will be independent and in duplicate, and which software tool you will use.
Risk-of-bias assessment: Name the specific appraisal tool for each study design category. State how many reviewers will complete the appraisal and how disagreements will be resolved.
Data synthesis plan: State whether you plan a meta-analysis or a narrative synthesis. If meta-analysis, state which effect measure, which statistical model, which software, and which heterogeneity statistics you will report. State any pre-specified subgroup and sensitivity analyses. If meta-analysis is not planned, state the synthesis approach and reference the SWiM guideline.
Reporting: State that you will follow PRISMA 2020 for PRISMA 2020 reporting requirements.
Table 2: Systematic Review Protocol Content Checklist
Protocol Section | What to Include | Common Mistake |
|---|---|---|
Research question | Full PICO question: Population, Intervention, Comparator, Outcome, and Timeframe. Written as a complete question, not a topic statement. | Vague topic statements ("a systematic review of exercise interventions") instead of a specific PICO question with a defined population and measurable outcome. |
Eligibility criteria: study types | Name every eligible study design. If including both RCTs and non-randomized studies, list both and name the appraisal tool for each design category. | Listing "randomized and non-randomized studies" without naming which specific non-randomized designs are eligible. |
Eligibility criteria: participants | Age range, diagnosis or condition with diagnostic criteria, clinical setting, relevant comorbidities or exclusions. Be specific enough that two reviewers would agree on every record. | Broad terms like "patients with diabetes" without specifying type, diagnostic criteria, age range, or setting. |
Eligibility criteria: outcomes | Primary outcomes first, then secondary. Name specific measurement tools or scales. Every outcome listed must be extracted and reported in the final manuscript. | Listing outcomes in the protocol that are never extracted or reported in the review — selective outcome reporting that GRADE penalizes. |
Search strategy | All databases, a full Boolean string for at least one database (as a supplement), a date range, a date search was run, all limiters, and grey literature sources to be searched. | Listing databases without providing the search string. Running the search before protocol registration. |
Risk-of-bias assessment | Name the specific tool for each study design (e.g., RoB 2 for RCTs; ROBINS-I V2 for NRSIs; QUADAS-2 for diagnostic accuracy). Number of reviewers and disagreement process. | Stating "we will assess risk of bias" without naming the tool, leaving the door open to selecting the tool after seeing the evidence base. |
Data synthesis plan | State whether meta-analysis or narrative synthesis is planned. If meta-analysis: effect measure, statistical model, tau² estimator (REML recommended), heterogeneity statistics, and software. Pre-specify all subgroup and sensitivity analyses. | Not specifying whether meta-analysis is planned or what heterogeneity thresholds will trigger narrative synthesis instead. |
Reporting standard | State that the review will be reported according to PRISMA 2020 (Page et al., BMJ 2021;372:n71). Include the PRISMA 2020 checklist as a supplementary file at submission. | Referencing PRISMA 2009 or the original PRISMA statement rather than the 2020 update, which is now the current standard. |
PROSPERO Field-by-Field Walkthrough
PROSPERO has 23 fields. The ones below are the most commonly misunderstood, the most frequently returned for revision, and the most important for the methodological credibility of your registration.
Review title: Write the title to describe the population, intervention, and review type precisely. Avoid vague titles like "A systematic review of nursing interventions." Prefer "A systematic review of nurse-led hand hygiene interventions on healthcare-associated infection rates in adult acute care settings."
Review question: This is the most important field and the most commonly vague. Write the question in PICO format as a complete question: "In adults aged 65 and over admitted to inpatient units (P), does a nurse-led structured hourly rounding protocol (I) compared to standard call-bell care (C) reduce inpatient falls per 1,000 patient days (O) during hospitalization (T)?" Every word in this field will be tested against your eligibility criteria during the CRD review.
Condition or domain: Name the specific condition, not a broad category. "Hypertension", not "cardiovascular disease." "Major depressive disorder", not "mental health conditions."
Intervention(s): Name the specific intervention and any variants you will include. Specify dose, duration, frequency, and delivery mode where those factors define the intervention. If you will include multiple variants, explain how you will handle them in the synthesis.
Comparator(s)/control: Specify what the intervention is being compared to. "Placebo" is insufficient if placebo procedures varied across trials. "No intervention," "usual care," and "active comparator" each imply different methodological considerations and should be specified separately.
Types of study to be included: List every eligible study design. If you plan to include both randomized and non-randomized studies, state both explicitly. Omitting non-randomized studies here and then including them later is a protocol deviation that requires amendment.
Main outcome(s): List only the primary outcome here. PROSPERO limits this field, and excess length prompts CRD reviewers to return the record. Additional outcomes go in the next field.
Data extraction (who and how): State "Two reviewers will independently extract data using a pre-piloted extraction form in [software]. Disagreements will be resolved through discussion, with a third reviewer adjudicating where consensus is not reached." Do not leave this field vague. It directly addresses whether your review meets dual-extraction standards.
Risk of bias assessment: Name the specific tool. "We will assess risk of bias using RoB 2 (Sterne et al., 2019) for randomized controlled trials and ROBINS-I V2 (November 2025) for non-randomized studies of interventions." Naming the tool and citation here prevents you from switching tools later without an amendment.
Stage of review at time of registration: Select "Ongoing" if any part of the review has not yet been completed. If your search has already been run, you must disclose this. Registering after completing the search is methodologically problematic and should be disclosed transparently in both the PROSPERO record and the final manuscript.
Anticipated or actual start date and completion date: Enter realistic dates. CRD uses these to follow up on overdue reviews. The average time from registration to publication is approximately 67 weeks (Borah et al., BMJ Open, 2017). Allow for this when planning completion dates.
Country: Select all countries where the review team is based, not where the included studies were conducted.
Funding sources: Declare all funding, including institutional support, grant funding, and any commercial funding. This field is a conflict-of-interest disclosure.
Conflicts of interest: Declare any financial or non-financial interests that could bias the review. If the review is supported by an organization with an interest in a particular finding, this must be stated.
Need support writing your PROSPERO protocol or eligibility criteria? |
|---|
Writing a PROSPERO registration that passes CRD review requires precise eligibility criteria, a fully specified synthesis plan, and a named appraisal tool for every study design category. Vague protocol fields are the most common reason registrations are returned, adding weeks to your project timeline. ScribeLab Writer's systematic review writing team supports researchers with full protocol development, PROSPERO submission, and eligibility criteria that meet Cochrane and PRISMA 2020 standards. |
What Happens After You Submit to PROSPERO
You receive a citable DOI immediately. As soon as you submit, PROSPERO generates a record with a unique DOI that you can cite in your methods section. The record is visible to others while under CRD review. Cite it in your paper as: "This systematic review was prospectively registered on PROSPERO (registration number CRDXXXXXXXX)."
CRD staff review your submission. The CRD team checks whether your submission falls within PROSPERO's scope, whether the required fields are sufficiently complete, and whether your review closely duplicates an existing registration. The 2025 PROSPERO relaunch introduced automated duplicate-topic detection that flags overlapping submissions at the point of entry, before CRD review begins.
You may receive a return for revision. CRD returns registrations that are out of scope, that have insufficient detail in key fields (most often the research question and eligibility criteria), or that appear to duplicate an existing record. A returned registration does not mean rejection. Address the specific comments, revise the fields indicated, and resubmit. Most returned registrations are published within days of resubmission.
Processing times have shortened. The 2025 platform relaunch introduced more automatic processing features. Check the current PROSPERO homepage at crd.york.ac.uk/prospero for the current average processing time.
Amending a PROSPERO Registration
Plans change during a systematic review. Databases become unavailable, outcome definitions shift when the evidence base does not use the originally planned instrument, or the eligibility criteria need to be narrowed because the initial scope would produce an unmanageable number of records. Amendments are expected and acceptable. Concealed deviations are not.
When to submit a formal amendment:
The research question changes in substance
Eligibility criteria change (adding or removing a study design, population category, or outcome)
Primary and secondary outcomes are switched
Databases to be searched are added or removed
The planned synthesis approach changes from meta-analysis to narrative synthesis or vice versa
When to disclose a deviation without amending:
Minor wording clarifications that do not change the scope
Adding a search date that was omitted from the original record
Updating the completion date
All deviations from the registered protocol, whether formally amended or not, must be transparently reported in the methods section of the final manuscript. PRISMA 2020 item 24a requires authors to report "any deviations from the review protocol, specifying the reasons." A reviewer who checks the PROSPERO record and finds undisclosed deviations in the manuscript will flag it as a methodological concern.
Common Protocol Mistakes That Delay or Sink Reviews
Registering after the search has already been run. This is the most consequential mistake. A post-search registration cannot prove that the eligibility criteria, outcomes, and synthesis plan were specified before the evidence was examined. If you have already started searching, register now, disclose the search start date accurately in the stage-of-review field, and note the timeline deviation in the final manuscript.
Vague eligibility criteria. "Adults with chronic disease" is not an eligibility criterion. "Adults aged 18 years and over with a confirmed diagnosis of type 2 diabetes (HbA1c above 6.5 percent or on antidiabetic medication), recruited from outpatient or community settings" is an eligibility criterion. The specificity matters because two reviewers must apply it independently and reach the same decision for every screened record.
Listing outcomes not planned for data extraction. If you list an outcome in the protocol and then fail to extract data for it in the review, you have committed selective outcome reporting. Either extract data for every listed outcome, or amend the protocol to remove outcomes you will not report before you begin data extraction.
Not pre-specifying the risk-of-bias tool. Stating "we will assess risk of bias" without naming the specific tool for each study design gives you no methodological commitment. If you then select the tool after seeing the study designs in your evidence base, the appraisal approach was not a priori.
Not pre-specifying subgroup and sensitivity analyses. Any analysis conducted after the primary synthesis that was not stated in the protocol is post-hoc and exploratory. Pre-specify every subgroup and sensitivity analysis you anticipate running. Add analyses to the protocol if you identify new reasons for them before data extraction begins.
Using the PROSPERO record as the only protocol document. PROSPERO's word limits make it a summary, not a full protocol. The full protocol should be a comprehensive document. Often 10 to 20 pages. that can serve as a supplementary file at journal submission. Some journals and all Cochrane editorial offices require the full protocol.
Protocol Standards Across Different Review Contexts
Cochrane reviews: All Cochrane reviews require a full protocol that is peer-reviewed and published in the Cochrane Database of Systematic Reviews before data collection begins. The Cochrane protocol is more detailed than a PROSPERO registration and must follow the Cochrane Handbook's protocol template. PROSPERO registration is also required for most Cochrane reviews.
Non-Cochrane journal submissions: Most journals require PROSPERO registration and ask authors to include the registration number in the methods section. Some journals (The Lancet, BMJ) require PROSPERO registration as a condition of peer review for systematic reviews. Submitting without a registration number to these journals leads to immediate desk rejection.
DNP and MSN capstone projects: US nursing programs require evidence synthesis that meets AACN Essentials (2021) competencies for doctoral-level practice. A registered protocol demonstrates that the evidence synthesis was planned a priori, which is a requirement for a DNP project to qualify as a scholarly product rather than an academic literature review. Many programs accept PROSPERO registration or an OSF registration, depending on the review type.
International research (UAE, Saudi Arabia, UK, Australia): PROSPERO is internationally recognized and accepted by research ethics boards, funding bodies, and journals in all four markets. The registration process is identical regardless of the author's institution's country. UAE and Saudi programs accredited by US bodies (SACSCOC, ACEN) follow the same PROSPERO standards as US programs.
Frequently Asked Questions About Systematic Review Protocols and PROSPERO
When is the latest I can register my protocol on PROSPERO?
Register before you run any database search. That is the only registration that qualifies as prospective. If you have already run searches, register as soon as possible, select "Ongoing" as the review stage, enter the actual date your search began, and disclose the registration-after-search timeline in your final manuscript. Late registration is not ideal, but it is far better than no registration.
Can I register my scoping review on PROSPERO?
No. PROSPERO does not accept scoping reviews, narrative reviews, or mapping reviews. Register your scoping review protocol on OSF at osf.io. OSF registration is instant, free, and provides a citable DOI. Your protocol remains editable with full version history, so any amendments are automatically tracked.
How long does PROSPERO processing take?
Processing times vary and have shortened since the 2025 platform relaunch, which introduced more automated processing. Check the current average processing time on the PROSPERO homepage at crd.york.ac.uk/prospero. In most cases, you receive a DOI immediately upon submission regardless of how long the CRD review takes.
Can two teams register a review on the same topic?
Yes, and it happens more often than researchers expect. PROSPERO's 2025 duplicate-detection feature flags overlapping submissions, but does not prevent them. If you discover a duplicate, read the existing registration carefully. If the populations, interventions, or outcomes differ sufficiently, both reviews may be valuable. If they are substantially identical, contact the other team to discuss whether collaboration or differentiation is appropriate.
Do I need a registered protocol if my institution does not require one?
Yes, for practical reasons beyond institutional requirements. Major journals (The Lancet, BMJ, JAMA) require PROSPERO registration as a condition of peer review for systematic reviews. Peer reviewers will ask for the registration number. Without one, your manuscript faces barriers at high-impact journals regardless of its methodological quality.
What is the difference between a protocol deviation and a protocol amendment?
A protocol amendment is a change submitted to PROSPERO and formally recorded in the registration before the change is implemented. A protocol deviation is a departure from the registered protocol that occurs without formal amendment. All deviations must be disclosed in the final manuscript under PRISMA 2020 item 24a. If you know a change is coming before you make it, amend the protocol. If you discover a deviation after the fact, disclose it transparently.
Can I publish my protocol as a standalone article?
Yes, and this is common practice. Journals including Systematic Reviews (BioMed Central), BMJ Open, and PLOS ONE accept protocol publications. Publishing the protocol provides additional peer review of your methods before the review is complete, strengthens the audit trail, and gives you a citable publication during a potentially long review process. Protocol publications also count toward academic output in performance reviews.
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Starting the Review Right
The systematic review protocol is not paperwork. It is the commitment you make to yourself and your readers that what you find will be reported as you planned to report it. Every element of the protocol, the research question, the eligibility criteria, the synthesis plan, the named appraisal tools, and the pre-specified subgroup analyzes, is a methodological safeguard against the accumulated small decisions that collectively bias a review.
Register before the search. Write the full protocol document, not just the PROSPERO summary. Pre-specify everything you plan to analyze. Amend formally when plans change. Disclose all deviations in the final manuscript.
A PROSPERO registration returned for vague eligibility criteria or an insufficient synthesis plan delays your review start date by weeks and creates a methodological gap that peer reviewers will find in the manuscript months later. ScribeLab Writer's systematic review writing team, led by credentialed researchers with published systematic reviews in the biomedical literature, works with research teams from PICO formulation through to a complete, CRD-ready PROSPERO submission, covering eligibility criteria, search strategy specification, risk-of-bias tool selection, and synthesis approach. Submit your research question and target journal through the enquiry form, and a member of the team will respond within 2-4 hours.
