Intended for healthcare professionals


When I use a word . . . Seeding trials

BMJ 2023; 381 doi: (Published 02 June 2023) Cite this as: BMJ 2023;381:p1270

Linked News

Give doctors financial incentives to take part in clinical trials, review recommends

  1. Jeffrey K Aronson
  1. Centre for Evidence Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
  2. Twitter @JKAronson

The recently published Lord O’Shaughnessy report on the conduct of commercially sponsored clinical trials of new medications in the UK contains 27 recommendations. Recommendation 22 reads “Financial incentives should be introduced for GPs to take part in commercial trials.” However, such payments, a feature of so-called seeding trials, have been considered unethical. Ethics committees should not approve any clinical trial in which investigators are given personal financial or other types of special incentives to take part in any way, including recruitment of patients.

Encouraging clinical trials

The recently published Lord O’Shaughnessy report on commercial clinical trials in the UK12 includes 27 recommendations relating to eight stated problems. In its response to the report, published simultaneously, the government supported the recommendations and gave details of its agreement to implement five of them, at a cost of about £120m over the next three years.3

Recommendation 22 in the report reads as follows: “financial incentives should be introduced for GPs to take part in commercial trials.”

Clinical trials in the community

Problem statement number 8 in the Lord O'Shaughnessy report states that “primary care is a negligible provider of clinical trial activity, despite the opportunities it provides for delivering population-scale trials, and there is too much reliance on hospital settings for the delivery of trials.” This statement is followed by a description of the PANORAMIC trial, citing it as a successful example of what can be done.

PANORAMIC was a UK based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial, in which eligible participants were either aged 50 years or older, or aged 18 years or older with relevant comorbidities, and had been unwell with confirmed covid-19 in the community for up to five days.4

In a PANORAMIC trial conducted between December 2021 and April 2022,5 12 821 participants were randomly assigned to molnupiravir plus usual care and 12 962 to usual care alone; of those, 12 529 and 12 525 participants respectively were included in the primary analysis population. Of 25 708 participants, 24 290 (94%) had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisation or death were recorded in 105 and 98 participants respectively and serious adverse events, not judged to be related to the intervention, were recorded in 50 and 45. Thus, molnupiravir was shown not to have reduced the frequency of covid-19-associated hospitalisations or deaths among high risk vaccinated adults in the community. The trial was funded by the UK National Institute for Health and Care Research (NIHR).

PANORAMIC is only one example of successful community based clinical trials carried out in the UK. Other examples include: the ASPIRE research programme, funded by the NIHR's Programme Grants for Applied Research programme6; a pragmatic cluster randomised controlled trial of implementation and evaluation of a patient centred intervention to improve the management of multimorbidity in general practice, funded by the NIHR's Health Services and Delivery Research programme7; and a randomised controlled trial of the effect of cognitive behaviour therapy versus non-directive counselling or usual GP care in patients with depression and mixed anxiety and depression, funded by the NHS Health Technology Assessment programme.8

Recommendation 22

Having enunciated the perceived problem that “primary care is a negligible provider of clinical trial activity,” and having outlined the success of the PANORAMIC trial, the report goes on to make a sensible recommendation: “NIHR and equivalent funding in the devolved governments should be used to create a network of primary care clinical trial networks [sic] to enable new forms of trial activity that are closer to the patient and increase opportunities for marginalised communities to take part in research.” There is no definition of “marginalised communities” in the report, but the recommendation could equally apply to all communities.

The recommendation continues “[Such networks] should ideally align with, or expand upon, the CPRD database, which provides primary care data for research purposes.” This makes sense. The CPRD, the Clinical Practice Research Datalink, previously the General Practice Research Database (GPRD), although nothing to do with recruiting patients to clinical trials, commercial or otherwise, collects anonymised patient data from GP practices across the UK, and can be used to pinpoint gaps in knowledge, prompting further appropriate research.9 And elsewhere it is observed that “there is also in place the NHS DigiTrials Service to recruit patients ….”

However, Recommendation 22 then continues with a statement that I regard as a non sequitur: “Primary care reimbursement regimes, such as the Quality and Outcomes Framework (QOF) in England, and similar systems elsewhere in the UK, should be used to provide financial incentives to GPs to take part in research activity.” Furthermore, the headline recommendation hovering over this whole paragraph, highlighted in bold, is limited to this final part: “Financial incentives should be introduced for GPs to take part in commercial trials.” The headline ignores the more appropriate recommendation—that more expert clinical trials sites should be established.

There is nothing new about the suggestion that doctors should be given financial incentives to take part in clinical trials. It is a feature of what have been called “seeding trials.”

Seeding trials

Seeding trials in clinical medicine are studies conducted by pharmaceutical companies, supposedly as legitimate scientific studies, but actually for the purposes of marketing a product rather than for the primary purpose of research.10 Payment of investigators may be involved, although not necessarily. Typically, such trials have been carried out after a medicinal product has been marketed, but the same strategy may be used at earlier stages. For example, an advertisement for a medicinal product that appeared in the British Medical Journal in 1952 stated that although clinical trials of the product were being conducted, the product had been made available to all hospitals and tuberculosis centres, “in view of the need for wider confirmation of early work [that demonstrated efficacy].”11 In another advertisement, in 1955, a company stated that it was “anxious to assist all those interested and will be pleased to make small supplies [of their product] available to those medical practitioners who may wish to carry out trials.” All this, of course, was before the process of marketing authorisation was introduced in the UK.

When Krumholz and colleagues discussed a published trial of gabapentin in patients with epilepsy, and which had turned out to be a seeding trial, they pointed out that “there is an inherent conflict of interest when an organization responsible for protecting human subjects subsists on payments from trial sponsors, potentially leading to companies shopping protocols to find the most receptive [ethics committee].”12 Other examples have been discussed elsewhere.13 Such trials are considered to be unethical, because they “deceive investigators, clinicians, and patients, subverting the scientific process and violating ethical norms.”14

This implies that, as a general principle, research ethics committees, known in the USA as institutional review boards (IRBs), should not approve any clinical trial in which investigators are given personal financial or other types of special incentives to take part in any way, including recruitment of patients.15

A final thought

Recruitment to clinical trials in the community, whether commercial or otherwise, is clearly not a problem that needs financial incentives to GPs. And, as has been pointed out elsewhere, “any payment [to GPs] is a potential inducement to consider actions other than those that are clearly in the best interest of an individual patient.”16

The government would better serve clinical trials in the community by establishing more clinical trials units, similar to that of the PANORAMIC Trial Investigators in the Primary Care Clinical Trials Unit in the Nuffield Department of Primary Care Health Sciences in Oxford, rather than by paying general practitioners to enrol patients in commercially sponsored clinical trials. That would allow both phase 3 trials and postmarketing trials to be efficiently carried out by clinical trials experts in the community. Indeed, that is what Recommendation 22 actually suggests, although the bold headline does not reflect that, and instead diverts attention from the more useful part of the recommendation.


  • Competing interests: JKA is a member of the Centre for Evidence Based Medicine in the Nuffield Department of Primary Care Health Sciences in the University of Oxford, but was not involved in the conduct of the PANORAMIC trials.

  • Provenance and peer review: not commissioned; not externally peer reviewed.