Background: Pharmaceutical companies fund the vast majority of the clinical research that is undertaken on medications but face a conflict of interest between producing good science and results that will enhance the sales of their products. Objective
Oncology drugs are frequently approved on the basis of surrogate outcomes that require further trials to confirm the benefits, but at times these trials fail and regulators need to decide whether to withdraw approval for the indication and/or to remove the drug from the market. This study compares decisions by the Food and Drug Administration and Health Canada about oncology drugs that were approved using either Accelerated Approval (FDA) or Notice of Compliance with conditions (NOC/c, Health Canada) and that failed confirmatory trials.Drug/indications approved by the FDA through its Accelerated Approval Pathway and that later failed confirmatory studies were identified from a published study and additional information on these drugs was collected from Drugs@FDA. Health Canada websites were searched on September 11, 2021 for the same group of drugs to determine if they were approved in Canada under the NOC/c pathway for the same indication as in the US. Information from both the FDA and Health Canada about these products was entered into an Excel spreadsheet. Decisions about whether to withdraw the drugs or remove the failed indication for the drug and requirements for confirmatory studies were compared. In addition, the dates of decisions by the two agencies were compared.Ten drug/indications were available for comparison. Regulatory decisions were similar in 4 cases, different in 1 case and could not be determined in the remaining 5, in 1 case because decisions were pending in both countries and in the other 4, because the NOC/c had not been fulfilled in Canada. The requirements for the confirmatory studies were similar in both countries. Decisions were made earlier in the United States.This study shows that decisions made by Health Canada and the FDA about whether to withdraw a drug or remove a failed indication when drug/indications fail a confirmatory trial are usually similar, although the sample size on which this conclusion is made is small. The clinical implications of these similarities and differences should be explored.
Although selective and incomplete publication is widely acknowledged to be a problem, full access to clinical trial data remains illusive. Authors’ personal files, key documents from Food and Drug Administration and European Medicines Agency and focussed searches of PubMed. Existing sources of information provide an incomplete overview of scientific research. Persistent arguments about commercial confidentiality and the potential difficulties in de-identifying raw data can block important progress. Current industry efforts are voluntary and only partially satisfy the need for complete data. Requirements for trial registration are increasing. Important regulatory changes in particular in Europe have the potential to result in the release of more information. Documenting the effects of prospective trial registration and requirements for proactive clinical trial publication on healthcare decisions, public health and rational resource allocation.
Abstract Background Thailand has expressed interest in joining the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP), a twelve-country plurilateral trade agreement whose original incarnation included the United States of America (USA). When the USA withdrew from this agreement, key intellectual property clauses relevant to pharmaceuticals were suspended. These could be reinstated should the CPTPP Parties decide to do so. Methods This study uses two scenarios to cost the impact the CPTPP would have had on Thailand’s 2020 hepatitis C treatment regime if Thailand joined the CPTPP and suspended clauses were reinstated. Results Joining the CPTPP could have increased the cost more than tenfold if suspended CPTPP clauses were reinstated and Thailand was not willing or able to issue compulsory licenses. Based on the 2020 budget, the price for this possible scenario could have reduced hepatitis C treatment coverage by 90%. Conclusions Acceding to trade agreements such as the CPTPP that require increasing intellectual property protection, could compromise Thailand’s hepatitis C program and other national treatment programs reliant on affordable generic medicines. The CPTPP could also prevent Thailand from relying on its own pharmaceutical capabilities to manufacture medicines needed to sustain its treatment programs.
In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information.We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95-701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6-14) than were solely industry funded trials.Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial registration to ensure completion of mandatory contact information fields identifying scientific leadership.
