Seeding Trials and the Subordination of Science

Alexander, G. Caleb

doi:10.1001/archinternmed.2011.232

Cited by 7 publications

(5 citation statements)

References 9 publications

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“…For instance, prior research has shown that many postmarketing trials were ‘seeding trials’, designed for marketing purposes rather than scientific relevancy. 7 8 The number of postmarketing studies per novel drug and planned enrolment were highly variable, but most studies were conducted in only one country and North America and Europe were by far the most frequent locations. Median planned enrolment was low and many studies were still not completed at the time of data acquisition.…”

Section: Discussionmentioning

confidence: 99%

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Postmarketing studies for novel drugs approved by both the FDA and EMA between 2005 and 2010: a cross-sectional study

et al. 2017

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ObjectivesTo characterise postmarketing studies for drugs that were newly approved by the US Food and Drug Administration and the European Medicines Agency.Design and settingCross-sectional analysis of postmarketing studies registered in ClinicalTrials.gov until September 2014 for all novel drugs approved by both regulators between 2005 and 2010. Regulatory documents from both agencies were used.Primary and secondary outcome measuresAll identified postmarketing studies were classified according to planned enrolment, funding, status and geographical location, and we determined whether studies studied the originally approved indication.ResultsOverall, 69 novel drugs approved between 2005 and 2010 were eligible for inclusion. A total of 6679 relevant postmarketing studies were identified; 5972 were interventional (89.4%). The median number of studies per drug was 55 (IQR 33–119) and median number of patients to be enrolled per study was 60 (IQR 28–183). Industry was the primary sponsor of 2713 studies (40.6%) and was a primary or secondary sponsor in 4176 studies (62.5%). In all, 2901 studies (43.4%) were completed, 487 (7.3%) terminated, 1013 (15.2%) active yet not recruiting, 1895 (28.4%) recruiting and 319 (4.8%) not yet recruiting. A total of 80% of studies were conducted in only one country and 84.4% took place in Europe and/or North America; 2441 (36.5%) studied another indication than the originally approved indication. Studies designed in the originally approved indication were found to be more industry-sponsored than others 68.7%vs53.7%; P<0.0001.ConclusionsPostmarketing pharmaceutical research was highly variable and predominantly located in North America and Europe. Postmarketing studies were frequently designed to study indications other than the originally approved one. Although some findings were reassuring, others question the lack of coordination of postmarketing research.

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Section: Discussionmentioning

confidence: 99%

“…Some research also suggested that a substantial proportion of postmarketing trials, even those with results eventually published in high-impact factor journals, were designed for marketing purposes rather than medical interest. 7 8 …”

Section: Introductionmentioning

confidence: 99%

Postmarketing studies for novel drugs approved by both the FDA and EMA between 2005 and 2010: a cross-sectional study

et al. 2017

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“…Moreover, including more patients than needed increases the familiarity of the participating physicians with the new drug, making it more likely that they will use it afterwards, a problem seen with ‘seeding trials’ (i.e. trials of approved drugs with limited scientific purpose) 14 …”

Section: Clinical Trial Methodologymentioning

confidence: 99%

A costly revolution for a subgroup of patients with metastatic melanoma

Akkooi¹,

Nijsten²

2013

British Journal of Dermatology

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Summary ORIGINAL ARTICLE: Hauschild A, Grob JJ, Demidov LV et al. Dabrafenib in BRAF‐mutated metastatic melanoma: a multicentre, open‐label, phase 3 randomised controlled trial. Lancet 2012; 380: 358–65. Background Dabrafenib, an inhibitor of mutated BRAF, has clinical activity with a manageable safety profile in phase I and II studies in patients with BRAF (V600)‐mutated metastatic melanoma. Hauschild et al. aimed to assess the efficacy of dabrafenib in a phase III trial of patients with BRAF (V600)‐mutated metastatic melanoma. Methods Patients were enrolled into a phase III trial between December 2010 and September 2011. This report is based on the cut‐off date of 19 December 2011. Patients with previously untreated stage IV or unresectable stage III BRAF (V600)‐mutated melanoma were randomly assigned (3:1) to receive dabrafenib (150 mg twice daily, orally) or dacarbazine (1000 mg m−2 intravenously every 3 weeks). Patients were stratified according to American Joint Committee on Cancer stage. The primary endpoint was investigator‐assessed progression‐free survival (PFS) and was analysed by intention to treat. Safety was assessed per protocol. Findings Of the 733 patients screened, 250 were randomly assigned to receive either dabrafenib (187 patients) or dacarbazine (63 patients). Median PFS was 5·1 months for dabrafenib and 2·7 months for dacarbazine, with a hazard ratio of 0·30 (95% confidence interval 0·18–0·51, P < 0·0001). At cut‐off, 107 (57%) patients in the dabrafenib group and 14 (22%) in the dacarbazine group remained on randomized treatment. Treatment‐related adverse events (grade 2 or higher) occurred in 100 (53%) of the 187 patients who received dabrafenib and in 26 (44%) of the 59 patients who received dacarbazine. The most common adverse events with dabrafenib were skin‐related toxic effects, fever, fatigue, arthralgia and headache. The most common adverse events with dacarbazine were nausea, vomiting, neutropenia, fatigue and asthenia. Grade 3–4 adverse effects were uncommon in both groups. Interpretation Dabrafenib significantly improved PFS compared with dacarbazine.

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“…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…”

Section: Seeding Trialsmentioning

confidence: 99%

When I use a word . . . Seeding trials

Aronson

2023

BMJ

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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.

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Seeding Trials and the Subordination of Science

Cited by 7 publications

References 9 publications

Postmarketing studies for novel drugs approved by both the FDA and EMA between 2005 and 2010: a cross-sectional study

Postmarketing studies for novel drugs approved by both the FDA and EMA between 2005 and 2010: a cross-sectional study

A costly revolution for a subgroup of patients with metastatic melanoma

When I use a word . . . Seeding trials

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