PROSPERO Registration for Systematic Reviews: What Medical Authors Need to Know in 2026

If you are writing a systematic review for a medical journal, you almost certainly need to register it in PROSPERO before you start extracting data. This is not a new requirement. PROSPERO has been running since 2011. What has changed is enforcement: Cochrane requires a registered protocol before a review can be submitted at all, and journals including the BMJ, The Lancet, JAMA Internal Medicine, and Annals of Internal Medicine now treat an absent or retroactive registration as grounds for desk rejection or at minimum for demanding an explanation that will follow the paper through peer review.

Meta-research published in 2026 tracking thousands of evidence synthesis records across PROSPERO, INPLASY, OSF, and other platforms found persistent gaps between what registration is supposed to accomplish and what authors actually submit. Protocols are sometimes registered only after the review is complete. Registered methods diverge from published methods with no explanation. Status fields go years without updates. These patterns matter because they undermine the core purpose of the registry: creating a verifiable, time-stamped record of what the review team intended before results were known.

What PROSPERO Is and Why It Exists

PROSPERO (Prospective Register of Systematic Reviews) is managed by the Centre for Reviews and Dissemination at the University of York. Registration is free and open to any researcher conducting a systematic review, scoping review, or rapid review with a health-related outcome. Each approved record receives a permanent identifier beginning with CRD42, which becomes the citation anchor you drop into your methods section.

The registry was designed to address a specific problem: selective outcome reporting in systematic reviews. Just as clinical trials can emphasize favorable endpoints and bury unfavorable ones, systematic reviews can be structured after the fact to arrive at pre-decided conclusions. The methods might look rigorous in the paper, but without a prospectively filed protocol there is no way for a reader, a reviewer, or an editor to verify that the research question, inclusion criteria, and primary outcome were set before the data were collected and analyzed.

This is a real problem. A substantial proportion of published systematic reviews do not match their registered protocols in ways that were never explained. Outcomes change between registration and publication. Search date ranges shift. Eligibility criteria narrow or expand. Sometimes those changes reflect legitimate refinements discovered during the review process, and some degree of deviation is expected. But undisclosed, unexplained deviations from a registered protocol are a signal of potential outcome switching, and peer reviewers at top journals now check for them systematically.

Which Journals Now Require Registration

The list of journals requiring a prospective PROSPERO record has grown considerably in recent years. Cochrane treats registration as a prerequisite, not a recommendation: a Cochrane review without an approved protocol cannot move forward in the Cochrane editorial process. For journals outside the Cochrane family, the standard is somewhat less uniform, but the trend is clearly toward mandatory registration rather than encouraged registration.

The BMJ requires a PROSPERO registration number for systematic reviews and meta-analyses, and its current instructions for authors explicitly note that the number must appear in the methods section. The Lancet family, including EClinicalMedicine and eBioMedicine, follows a similar policy. JAMA Internal Medicine and Annals of Internal Medicine both require prospective registration, and many other JAMA Network titles strongly recommend it to the point where peer reviewers will request it if it is absent.

Beyond these flagship titles, many specialty journals have added registration requirements in the past two years. Reviews in cardiology, oncology, psychiatry, and emergency medicine are particularly likely to encounter mandatory registration requirements, partly because the fields have been concerned about replication problems and outcome switching in their systematic review literature. If you are submitting to a specialty journal and cannot see a clear statement about registration in the author instructions, it is worth emailing the editorial office before you begin the review, not after.

The Timing Rule That Trips Everyone Up

The single most common PROSPERO compliance failure is not failing to register at all. It is registering too late. PROSPERO requires submission of your protocol before data extraction begins. The operative word is extraction, not publication or even screening. Once your team has started pulling data from included studies, the registration window has closed. Any record submitted after that point will be flagged as retrospective and will undermine the credibility of the registration itself.

Many research teams misread this rule as meaning "register before you submit the paper," which is technically later than required and sometimes dramatically so. If your team spent three months extracting data before registering, a reviewer who notices the date discrepancy between your registration timestamp and your described search dates will ask about it. That question rarely has a comfortable answer.

The correct workflow is to register as soon as your protocol is stable enough to describe your research question, eligibility criteria, search strategy, and planned analyses. Ideally this means registering before your first database search, though PROSPERO technically permits registration between the search and the start of screening. What it does not permit, and what should be treated as a hard stop, is registering after screening and data extraction have begun.

If you realize mid-review that you have not yet registered, stop and register immediately, then disclose the timing honestly in your methods section. Journals are more understanding about a brief delay with a candid explanation than they are about a registration date that looks deliberately misleading. The explanation should describe why registration was delayed, confirm that extraction had not begun, and note any minor modifications made to the protocol in the interim.

What Your Registration Record Must Include

PROSPERO requires you to fill in a structured form that covers the key methodological commitments of your review. The form is more detailed than it appears from the outside: there are around 30 fields, several of which require substantive text rather than a single-word answer. Reviewers and editors sometimes read the PROSPERO record directly, not just the CRD number, so vague or incomplete entries reflect on the review.

The most important fields are those that define scope and methods: your review question (including population, intervention or exposure, comparator, and outcome), your eligibility criteria, the databases you will search and your date range, whether you will include grey literature, your plan for risk of bias assessment, and your statistical synthesis method. If you plan a meta-analysis, specify your primary outcome and how you will handle heterogeneity. If you are conducting a narrative synthesis, say so and explain why quantitative pooling is not appropriate.

Do not leave fields blank that should be filled. A common shortcut is to enter "not applicable" or "TBD" in fields that require genuine method decisions. This is precisely what peer reviewers look for when they want to determine whether a protocol was written with the rigor of a prospective plan or drafted quickly after the fact. A registration record that reads as though it was written after the methods were already chosen tells that story clearly.

How the Registration Process Works

Registration at PROSPERO is free. You create an account at the University of York's CRD website, complete the structured form, and list all team members who are authors on the anticipated review. Each listed author receives an email from the system asking them to approve the record before it goes live. This step trips up review teams that wait until a deadline is close: if a co-author is traveling or slow to respond, your registration can be held up for days.

Build the author approval step into your timeline. Register when you have at least a week of runway before you need the CRD number in hand. Once all authors have approved the record, automated checks run and the record typically goes live within a few days, though delays can occur during high-volume periods. PROSPERO does not guarantee a review of every registration by a human editor before publication; many records go live after automated checks alone. However, records can be flagged for additional review if they appear incomplete or if there is a conflict with an existing registration.

After the record is live, you will receive your CRD identifier. Keep a copy with your review files. The identifier goes in the methods section of your paper, typically in the protocol and registration subsection, in a sentence such as: "This review was registered in PROSPERO (registration number CRD42XXXXXXXXXX)." Some journals also ask you to enter it in a specific field in the submission system, separately from the manuscript body.

What Peer Reviewers Actually Do With Your Registration

Experienced systematic review reviewers at journals like the BMJ, JAMA Internal Medicine, and Systematic Reviews will look up your PROSPERO record directly during peer review. This is not a perfunctory check. They compare your registered protocol to your published methods, looking specifically for unexplained changes in the primary outcome, eligibility criteria, statistical approach, or search scope.

Deviations between the protocol and the paper are not automatically fatal. Clinical research regularly discovers at the outset of a review that the original protocol needs refining: a search reveals that studies in a subpopulation are far more numerous than expected, or a planned meta-analysis is abandoned because the included studies are too heterogeneous to pool. What matters is transparency. Deviations must be acknowledged in the methods, explained, and where relevant characterized as either pre-planned amendments or unplanned post-hoc changes.

When a reviewer finds a meaningful change that is not acknowledged in the paper, the typical response is a major revision request asking for a thorough explanation. When the change involves the primary outcome and happens to have moved from a null result to a significant one, the editorial response is likely to be more serious. Some journals use a standard deviation table between registered and published methods as part of the standard submission requirements for systematic reviews, modeled on the approach used by CONSORT for clinical trials. If the journal you are targeting does not use such a table, submitting one voluntarily is a credibility signal.

Alternatives to PROSPERO

PROSPERO has the longest track record and is the most widely recognized platform, but it is not the only option. For certain types of evidence synthesis, or for teams that need faster registration, alternatives may be appropriate.

INPLASY (International Platform of Registered Systematic Review and Meta-analysis Protocols) was launched by a Chinese research consortium and has grown substantially in recent years. Registration is faster than PROSPERO, often taking hours rather than days, but it carries a small processing fee. Some journals explicitly accept INPLASY registration numbers in place of or alongside a PROSPERO number; others do not yet recognize it as equivalent. If your target journal is outside the major US and UK flagship titles, check its instructions before assuming INPLASY will satisfy the requirement.

The Open Science Framework (OSF) Registries accept any study type, including systematic reviews, and are frequently used by researchers in the behavioral and social sciences. OSF registration is free, instant in terms of creating a record, and creates a time-stamped version of your protocol document. For some journals and some study types, OSF is a recognized alternative. However, OSF does not screen protocol content for completeness or plausibility, and the records are less structured than PROSPERO, which can make them harder for reviewers to navigate.

Research Registry is a general-purpose research registration platform that accepts systematic reviews along with other study types. Like INPLASY, it charges a fee. For evidence syntheses specifically in healthcare, PROSPERO remains the first choice when journal requirements allow it, because it is most likely to be recognized by peer reviewers and editors across medical and public health journals worldwide.

Common Mistakes Worth Avoiding

Beyond registering too late, there are a handful of other errors that create problems later. Not updating the record is one of the most common. PROSPERO has a status field that should reflect the current stage of your review, and a record that has been sitting at "ongoing" for four years while the published paper appears in print creates unnecessary questions for anyone who checks. Update your record when the review concludes, and link to the published paper when it is available.

Registering a review that is not eligible for PROSPERO is another issue that sometimes surfaces at peer review. PROSPERO accepts systematic reviews and rapid reviews with health-related outcomes. It does not accept scoping reviews, literature reviews that are not systematic, or meta-analyses of aggregate non-health data. Authors sometimes register a protocol that does not match the actual review type, either through misunderstanding PROSPERO's scope or by registering a "systematic review" when the planned work is closer to a narrative review. This creates problems later when the published paper's methods do not match the registered protocol's claims.

Not listing the correct authorship team on the registration is a subtler problem. PROSPERO records the team that registered the review, and if authorship changes substantially between registration and publication, that discrepancy can trigger questions. This is particularly relevant in multi-site or multi-institutional reviews where early contributors may drop off. The PROSPERO record does not need to be identical to the published author list, but significant additions or removals should be noted and consistent with your journal's authorship policies.

Scoping Reviews and Other Evidence Syntheses

Scoping reviews have grown substantially in the medical literature over the past several years, and with that growth has come increasing attention to their methodological transparency. PROSPERO does not accept scoping reviews, because they do not typically test a defined hypothesis and so the concept of outcome-switching does not apply in the same way. However, many journals now ask authors of scoping reviews to register their protocol in OSF or a comparable platform, and the Joanna Briggs Institute provides guidance on protocol registration for scoping reviews alongside its scoping review methodology guidance.

Rapid reviews, which use streamlined systematic review methods to produce faster evidence summaries, are eligible for PROSPERO when they cover health-related outcomes. Given that rapid reviews are often commissioned to inform time-sensitive policy decisions, registering the protocol is important for establishing that the methods were not adapted to produce a particular answer.

Living systematic reviews, which update continuously as new evidence emerges, require registration as well, and the registration record itself needs to note the living design. PROSPERO accommodates living reviews, and the registration number for a living review should be the same number cited across all updates rather than generating a new CRD identifier each time the review is updated.

A Pre-Registration Checklist for Medical Systematic Reviews

Before opening the PROSPERO registration form, your team should be able to answer every item on the list below. If any item is still unresolved, settle it first. The protocol that emerges from this exercise is roughly what the PROSPERO form will ask you to describe.

The practical implication of all of this is straightforward: write your protocol early and register it before the work starts. That sounds obvious, but systematic reviews are the one study type where a meaningful proportion of teams still treat protocol development as a retrospective exercise. The journals that matter most to most medical researchers have closed that option. The reviewers who handle systematic review manuscripts know what a retroactively constructed protocol looks like and they will say so in their reports.

A registered protocol is not a constraint on good science. Methods evolve, and PROSPERO is designed to accommodate that through its amendment process. What registration does is force a team to think through its methods before data shapes those decisions. That is good for the review, good for readers, and increasingly a condition of publication at the journals where the evidence genuinely matters.

Further Reading