Our study aimed at evaluating variables associated with patient willingness to participate in different categories of clinical trials and at identifying a potential recruitment bias in clinical trials related to patient distrust in the pharmaceutical industry and healthcare systems.
For this purpose, we conducted a two-part analysis in respiratory disease patients surveyed about their opinions concerning clinical research and potential willingness to participate. The majority of patients surveyed suffered from chronic airway diseases (asthma, chronic obstructive pulmonary disease (COPD), i.e. the most prevalent chronic respiratory diseases in France .
First, we compared patient characteristics on the basis of their level of trust in the pharmaceutical industry. In a second step, we assessed willingness-to-participate in clinical trials for our whole population to identify factors associated with acceptance or refusal. Several studies have previously evaluated such rates and highlighted that altruism, hope for personal benefit, contribution to advances in science as well as financial benefit are the main reasons for agreeing to participate, whereas fear of adverse events, impossibility to cope with the logistic constraints accompanying participation, poor knowledge about or negative perception of clinical trials and distrust in pharmaceutical industry are potential barriers [20,21,22,23].
Thus, distrust in pharmaceutical companies was suspected to decrease patient willingness to participate in clinical trials but, to our knowledge, this has never been confirmed by juxtaposing patient-reported willingness-to-participate and their level of trust in pharmaceutical companies.
We found that 35.5% of respiratory disease patients declared they did not trust pharmaceutical companies. One major finding is that the profile of the latter, “distrusting” patients significantly differs from trusting patients: distrust is associated with female gender, inactive professional status and lack of knowledge on one’s own disease.
In the second step of our analysis, we calculated rates of willingness to participate in clinical trials. Such rates reported in medical literature are extremely heterogeneous [20,21,22,23,24,25]. This variation seems to depend on certain study characteristics: for example, willingness increases with disease severity . Clinical research is a wide and heterogeneous area with multiple methodologies, interventions and objectives. Referring to “clinical trials” as a single concept is simplistic. Similarly, considering willingness-to-participate in a specific subcategory of clinical trials in order to assess global perceptions of clinical research may be misleading.
Because we distinguished different categories of clinical trials in our survey, we were able to identify trial-category-related barriers and associated differences in patient profiles. Thus, the overall rate of willingness-to-participate in at least one category of trial was very high (93%) among the 838 surveyed patients we analyzed. Globally, patients are not reluctant to join clinical research but, as expected, we found rates that vary significantly depending on the type of trial (intervention tested, market status of the drug and type of trial sponsor) ranging from 11 to 86%. Refusal of drug trials was associated with sex, women being more reluctant to join drug trials than men. Among drug trials, an important difference exists in patient willingness-to-participate between pre-marketing and post-marketing studies. Only 29% of patients we surveyed would have accepted enrolment in a pre-marketing drug trial, while 75% would have participated in a post-marketing trial. We assume this highlights patient trust in the regulatory health authorities responsible for marketing approval. Poor knowledge about one’s own disease and distrust in the pharmaceutical industry were associated with the refusal of pre-marketing drug trials, but played no role in refusing post-marketing trials.
When comparing willingness-to-participate among different types of clinical trial sponsors, we found consistent results with only 11% of patients considering participation in industry-sponsored trials, while 86% would have agreed if the sponsor were academic. Again, distrust in pharmaceutical companies plays a role in this difference. This is a major finding which, to our knowledge, has never been identified previously. It may also present a lever for external validity improvement in industry-sponsored trials. Thus, targeted educational programs for improving knowledge on both diseases and clinical trials, as well as unbiased media communications about the benefits and risks of collaboration with pharmaceutical companies, could restore patient trust in pharmaceutical companies and increase willingness-to-participate in clinical trials. A joint effort for education and communication involving mass media, the pharmaceutical company, regulatory authorities and physicians is crucial for both current and future public health.
Additionally, post-marketing academic trials should be encouraged as well as pooled analyses of industrial and academic results.
The main limitation of the present survey is that it was conducted on a specific patient population, i.e. chronic respiratory disease patients. The results should not be extrapolated beyond chronic diseases which are not life-threatening in the short term. The second specificity is that the patients surveyed, living in France, have access to a robust health system which covers the costs of medical care and treatment. In some countries, participation in a clinical trial may be the only way to access care and treatment. Our study does not analyze if the barriers to participation that we have identified are likely to influence decision-making in this context.
One other limitation of our survey was that we assessed the hypothetical intention to participate, which has been shown to be higher than real participation rates . Some patients who declare they would accept participation may refuse once the offer to participate becomes real. We hypothesize that this situation may occur in any subgroup of patient and thus assume that the ranking of rates among trial subcategories, as well as refusal risk factors, are accurate.
The questionnaire was developed specifically in French for this study and has not been previously published in any peer-reviewed journal. A bilingual version, provided without cultural validation of the translation, is available as additional file.
In short, our results suggest that patient distrust in the pharmaceutical industry could help explain recruitment bias in industry─sponsored clinical trials conducted in similar settings. Attention should be paid to this phenomenon because the majority of therapeutic innovations are provided by pharmaceutical companies able to invest significant resources in research and development . Moreover, we found that patient distrust is associated with a distinct patient profile. Thus, we have no guarantee of the applicability of trial results for these patients. The under-representation of women, minorities and patients with poor health literacy in industry-sponsored clinical trials has recently gained awareness [26,27,28,29] and may threaten the generalizability of results . However, there is still very little available data focusing on women enrolment by country or disease. In the French asthma population for example, percentages of women enrolled are higher in women in France in a national academic interventional cohort than in a national industry led early access program to mepolizumab (64.5 and 45%, respectively) [30, 31]. Some data suggest that this under-representation of women exists worldwide even in countries where patients might be willing to participate in trials only to have their treatment free of charge [32, 33].
In this survey, we were not authorized to collect ethnicity, so we cannot conclude on this specific characteristic. However, we found that women and patients with poor knowledge concerning their disease were more likely to distrust pharmaceutical companies and are less willing to participate in industry-sponsored trials. This could at least partly explain underrepresentation of these sub-populations in industry-sponsored clinical trials and could be addressed by implementing educational strategies [34,35,36] as mentioned previously.
The publishing process of the present manuscript takes place during the COVID-19 pandemic period. It is difficult to anticipate how the current situation will shape and modify patients’ perception of pharmaceutical companies. Trusting opinions associated with the hope that pharmaceutical companies will find a treatment and distrusting opinions that accuse such companies of taking advantage of the situation to make money coexist. This should be the endpoint of a specific future study.