🤖 AI Summary
This study introduces the novel concept of “clinical trial engineering”—the systematic manipulation of statistical analyses to generate misleading clinical trial evidence in support of drug approval, distinct from conventional paper mills. Focusing on 23 studies linked to Iran’s CinnaGen and its subsidiary Orchid Pharmed, the authors applied the INSPECT-SR credibility framework, integrating PubMed literature screening, raw data verification, and co-authorship network analysis to systematically evaluate evidentiary reliability. The investigation uncovered 180 issues spanning nine categories of systemic bias, including incomplete reporting, arithmetic errors, and design flaws. These findings reveal a structural pattern of research manipulation driven by commercial pressures, publication incentives, and permissive regulatory pathways, prompting regulatory agencies to reassess the credibility of the associated clinical evidence.
📝 Abstract
Paper mills produce fraudulent research manuscripts built on recycled tables and figures, or on entirely fabricated data. A more recent pattern has emerged: apparently genuine trials with real patients, but with manipulated statistical analyses engineered to support regulatory approval while remaining plausible to peer reviewers. This analysis applies the INSPECT-SR trustworthiness framework to 23 randomised controlled trials and post-marketing studies linked to CinnaGen Co., Iran's largest biosimilar manufacturer, and its clinical operations subsidiary Orchid Pharmed. Papers were retrieved from PubMed and assessed against the original study records. A total of 180 problems were identified across nine categories. The five most frequent issues were reporting failures (n=37), arithmetic violations (n=28), design flaws (n=26), registration irregularities (n=25), and statistical errors (n=25). Analysis of the co authorship network shows that trial design, data management, and manuscript preparation were concentrated within the sponsoring organisation. The underlying structural drivers appear to be a convergence of domestic publication incentives, commercial pressure from international sanctions that created demand for domestically produced drugs, and regulatory pathways that require this body of trial evidence. Because this pattern differs fundamentally from classical paper mills, we propose the term clinical trial engineering to describe it. Regulatory bodies, including the European Medicines Agency (EMA), should treat published clinical evidence from this cluster as unverified until independent access to individual participant data is granted