Clinical studies of inhaled corticosteroids funded by the pharmaceutical industry are less likely to report adverse effects than those funded in other ways, a new study published in the Archives of Internal Medicine shows.
Even when statistically significant differences emerge, industry-funded studies tend to place a “more favourable clinical interpretation” on the results, the study found. The authors called for stronger disclosures of conflicts of interest.
The researchers assessed safety reporting in 275 studies of inhaled corticosteroids funded totally or partially by the manufacturer of the drug being investigated and 229 trials that received no funding from the sector. In the latter cases, a non-profit scientific or government agency funded the trial or the authors did not declare funding. The studies were published between 1 January 1993, and 31 December 2002.
Only 34.5% of studies funded by the pharmaceutical industry reported statistically significant differences in adverse effects between the active and control arm. This was about half the level in studies with no funding from the sector (65.1%). Furthermore, just 26.5% of studies funded solely by the manufacturing company showed significant differences in adverse effects between the active and control arms. This compared with 71.4% of studies with mixed funding.
The analysis also revealed a number of differences in design between pharma funded and non-company funded studies. For example, studies backed by a pharmaceutical company were more likely to be randomised clinical trials or multicentre studies; to enrol adults; study rhinitis; use a parallel design; have efficacy as the primary objective; use lower dosages; have a larger sample size and shorter follow-up; and assess adverse effects using non-specific clinical and/or laboratory data or cortisol metabolism.
On the other hand, pharma funded studies were less likely to enrol patients with asthma or to study specific adverse effects, such as growth or bone metabolism.
Against this background, the authors suggested study designs that tend to be associated with less frequent adverse events are more common among trials funded by the pharmaceutical industry. After controlling for this, the association between funding and adverse event reporting became non-significant.
The authors’ classified the interpretation of adverse effects into three categories: 'no comments', 'absent or unimportant' (e.g., comments such as 'safe' and 'well tolerated'), and 'adverse effects need to be considered'. In trials that found a statistically significant increase in adverse effects associated with the study drug, those funded by the pharmaceutical sector were almost four times more likely than studies with other funding sources to conclude that the drug was safe.
“Funding by the industry is associated with design features less likely to lead to finding statistically significant adverse effects and with a more favourable clinical interpretation of such findings,” the authors concluded. “Disclosure of conflicts of interest should be strengthened for a more balanced opinion on the safety of drugs.”
They suggested that “it might be desirable to require the disclosure of source of funding in the abstract”, the only part of a paper available to many clinicians.
Nieto A, Mazon A, Pamies R et al. Adverse Effects of Inhaled Corticosteroids in Funded and Nonfunded Studies. Arch Intern Med 2007;167:2047-2053