Our Times — Health

Half of Registered Clinical Trials Still Never Report Their Results

Priya Nair — Sat, 01 Aug 2026 00:00:00 GMT

Trial registration was designed to solve a specific and well-documented fraud: running a study, disliking the result, and never publishing it. Registering a trial before it starts creates a public record that it existed, so an absent result becomes visible as an absence. The mechanism is sound and it has been mandatory in most major jurisdictions for years. Compliance with the reporting half of it remains roughly a coin flip.

The registry now documents the problem it was built to prevent, in considerable detail, and very little happens as a result.

What the requirement says and what happens

The obligation is not complicated. Register the trial with its primary outcome before enrolment, and post summary results to the registry within twelve months of completion. Publication in a journal is separate and additional; the registry posting is the floor.

Audits across registries and jurisdictions keep landing in the same range. Roughly half of completed trials have results posted within the required window. A meaningful share never post at all. And a further category posts results that do not match the registered primary outcome, which is a different failure with the same effect.

Non-reporting is not random. Trials with unfavourable or null results are less likely to be reported, which is precisely the bias registration was meant to remove.
Academic sponsors perform worse than industry in most audits, which surprises people who assume the incentive problem is purely commercial.
Outcome switching is under-measured because detecting it requires comparing the registered protocol against the published paper, which almost no one does routinely.

The registry entry said the primary outcome was mortality at ninety days. The paper reported a composite endpoint that included hospital readmission. Both documents are public. Nobody had compared them in four years.

Why the evidence base is distorted, quantitatively

The consequence is not abstract. Meta-analyses and clinical guidelines are built from published trials. If unfavourable results are systematically missing, pooled estimates of treatment effect are biased upward, and the direction of the bias is known even when its magnitude is not.

Analyses that have recovered unpublished data through regulatory submissions or litigation have repeatedly found smaller effects than the published literature indicated, and in several well-known cases harms that the published record did not reflect. Each of those recoveries required a specific investigation. There is no routine mechanism for it.

Enforcement exists on paper

The relevant statutes and regulations do provide for penalties, including substantial daily fines in some jurisdictions. Enforcement actions are exceptionally rare relative to documented non-compliance.

The reasons regulators give are consistent: limited staffing, ambiguity about which entity is the responsible party for multi-site academic trials, and definitional questions about completion dates that make the twelve-month clock arguable. Those are real administrative obstacles. They are also the kind of obstacles that get resolved when there is institutional will, and the pattern suggests there is not much.

What has demonstrably worked is public tracking. Independent audits that publish sponsor-level compliance rates by name have produced measurable improvements at named institutions, on a timescale of months. Reputational pressure has outperformed statutory penalty in this domain by a wide margin, largely because it is actually applied.

What would fix it

Three changes would address most of the gap, and none require new legislation.

Tie funding and ethics approval to prior reporting compliance. An institution seeking approval for a new trial should demonstrate that its completed trials have posted results. This makes the sanction automatic and administrative rather than dependent on enforcement discretion.

Require registries to flag outcome discrepancies mechanically. Comparing a registered primary outcome against a reported one is a structured data problem, and doing it automatically would make outcome switching visible without anyone having to investigate.

Publish sponsor-level compliance as a standing metric rather than as periodic studies. The evidence that this works already exists.

The underlying pattern generalises beyond medicine. As we reported on the validation gap in protein design, any field where negative results go unrecorded will systematically overestimate how well its methods work.

The Antibiotic Pipeline Is Failing for Economic Reasons, Not Scientific Ones

Priya Nair — Tue, 30 Jun 2026 00:00:00 GMT

The standard account of antimicrobial resistance describes a scientific failure: bacteria evolve, discovery is hard, the pipeline is empty. The first two claims are true and the third is misleading. Novel antibiotics have been discovered, developed, and approved over the past decade. Several of the companies that brought them to market then went bankrupt, sometimes within two years of approval.

That is not a discovery problem. It is a revenue model that is structurally incompatible with responsible use of the product.

The conservation paradox

For most pharmaceuticals, a superior product should be prescribed widely. For a novel antibiotic effective against resistant organisms, the correct clinical and public health behaviour is the opposite: hold it in reserve, use it only when older agents fail, and thereby preserve its effectiveness for as long as possible.

Stewardship programmes exist specifically to enforce that restraint, and they work. They also mean that a successful new antibiotic, judged by public health value, generates minimal sales volume.

Revenue scales with use, and appropriate use is deliberately minimised.
Treatment courses are short. A week or two of therapy, compared with years of a chronic medication.
Price resistance is severe. Antibiotics are benchmarked against generics costing very little, so premium pricing meets institutional resistance regardless of novelty.
Patent life burns during reserve. Exclusivity runs while the drug is deliberately unused, so peak sales arrive after generic entry becomes possible.

We built the thing the guidelines asked for, and the guidelines then correctly instructed hospitals not to use it. There was no version of this where we made money.

What happened to the companies

The pattern has repeated enough to be predictive. A small company takes a novel agent through clinical development, secures approval on the strength of activity against resistant organisms, and then discovers that hospital formularies are slow to add it, stewardship committees restrict it appropriately, and annual revenue lands one or two orders of magnitude below what was needed to service development debt.

The company is sold at a loss or files for bankruptcy. The asset transfers to a larger firm that keeps it on the shelf, or in some cases withdraws it. The clinical need it addressed remains unmet in practice even though a licensed product exists.

Large pharmaceutical companies drew the obvious conclusion years ago and mostly exited antibacterial discovery. The remaining pipeline sits with small firms and academic groups that will face the same economics on approval.

The proposed fixes, and their track records

Two categories of intervention have been tried. Push incentives subsidise development: grants, non-dilutive funding, and public-private partnerships for early research. These have worked reasonably well at their stated purpose, which is why there are candidates at all.

Pull incentives are supposed to reward approval, and they are where the model still fails. Extended exclusivity does little when the constraint is volume rather than competition. Priority review vouchers are tradeable and have produced real value, but they are a one-off payment poorly matched to the size of the gap.

The mechanism with the strongest logic decouples payment from volume entirely. Under a subscription or availability model, a health system pays a fixed annual sum for guaranteed access to an antibiotic regardless of how much is dispensed. The developer receives predictable revenue; the health system retains every incentive to restrict use.

Pilot programmes in a small number of national health systems have demonstrated that this is administratively workable. The limitation is scale. A subscription from one or two countries does not underwrite global development costs, and the coordination problem across payers has not been solved.

What to watch

Two indicators matter more than pipeline counts. The first is whether subscription-style procurement expands beyond pilots to a group of payers large enough to constitute a viable market. The second is whether any newly approved agent reaches profitability under current arrangements, which so far none has.

Until one of those changes, additional research funding will continue producing approved drugs that bankrupt their developers. For the parallel problem of evidence that never reaches the public record, see our reporting on unreported clinical trials.