Yves Geysels

Since its inception, the process of informed consent has evolved incredibly. However, many barriers remain, preventing the smooth and efficient processes we would like to see in clinical trials (CTs).

The use of electronic informed consent could contribute to overcoming some of these inefficiencies, notably by increasing the flexibility of the process, thus allowing the informed consent document to be better adapted to the patient's needs and facilitating document and process management for study teams. However, the eConsent process is still not widely adopted. We see a number of reasons for this. Firstly, patients are not always comfortable with such technologies. Secondly, the first investment often frightens organizations. Thirdly, countries do not always recognize and allow electronic signatures. Finally, the requirements laid down by regulatory authorities still vary from region to region, country to country, and from one ethics committee to another.

On the opposite, under the increasing digitalization of our world and following the current pandemic, experts claim the necessity of such tool. Many trials had to improvise after the lockdown announcement: sites were suddenly closed, no one could access the documents nor the data, and CRAs were stuck at home.

The recruitment rate of clinical studies, which was already a critical point for trial success, has significantly decreased during this health crisis.

 Patients are stuck at home and cannot come on sites to meet the PI and receive the trial’s information. In addition, the COVID-19 pandemic resulted in a huge shift in the priorities of clinical staff members who needed to focus on COVID units and dedicated clinical trials.

 Consequently, the rate of trials’ enrollment at the end of June 2020 had plummeted from 30% compared with October 2019.

In the recent release (9.0) of “The Medidata Perspective” on the impact of COVID-19 on clinical trials (September 21, 2020), trial sites were asked to evaluate the impact of the pandemic on diverse activities within their studies. On a scale from 1 to 5, the biggest impacts were the sites’ ability to recruit patient (3.02) and to enroll patients (3.02). In response, 39.2% of sites decided to stop recruitment for ongoing trials.

 Nevertheless, this kind of decision is followed by important clinical trial delays and massive expenses.

The eConsent, or digital informed consent, thus appears as a promising solution. More and more CTs stakeholders are showing an interest and are turning to these new tools. Times are changing and we need to evolve with it. For some companies, the digital informed consent is now an integral part of the risk mitigation plan.

However, at the same time, the authorities must ensure that they can judiciously supervise the use of electronic tools. In many cases this calls for a complete revision of existing laws and regulations; it has already been done in the past for some technologies, as for the regulation of electronic signatures, but much more important revisions, such as the 3rd revision of ICH GCP, are underway for the complete integration of the various aspects of emerging technologies.

In the scope of this research project entitled “Toward a global implementation of eConsent in clinical trials”, a survey was conducted to understand how eConsent is perceived and experienced by clinical research experts, how it can improve patient comprehension, reduce site burden as well as to identify areas of opportunities and challenges for further adoption. The survey was based on a prospective questionnaire on eConsent, built to target five types of stakeholders: sponsors, contract research organizations (CROs), ethics committees (ECs), investigational sites (ISs), and vendors of eConsent solutions. The questionnaire was sent to clinical research experts in Belgium, Luxembourg and the Netherlands as, although three bordering European countries, they present disparities in the regulation and acceptance of eConsent.

The survey was sent between September 22, 2020 and November 1, 2020. In total, 342 participations were registered. Of them, 129 were complete responses and 213 were partial responses. Results were analyzed between November 5, 2020 and December 8, 2020.

Overall, the experience with eConsent among the targeted countries and the different stakeholders appeared quite different, but still very low for all of them. On average, 28% of the clinical research experts were novices with eConsent and only 3% had experience. Between the three countries, the Netherlands seemed to be the one with most expertise, followed by Luxembourg and Belgium.

Comparing the stakeholders, each seemed to have a different experience, but overall, very few answered being in full operational usage (~7%). Sponsors were the ones who were most in a pilot phase (~50%). However, half of Sponsors in piloting phase is still very low. The current lack of a uniform regulatory framework around eConsent on a European level appeared to be a rational explanation. In fact, when stakeholders were asked what the main barrier limiting the implementation of eConsent at their organization is, many Sponsors explained that the fragmented guidelines and regulations has considerably hindered their use of eConsent.

Another important barrier that stood out for Sponsors, but also CROs and ISs, was the concern about data privacy and security (~42%). Surprisingly, according to Vendors of eConsent solutions, the main concerns of the customers were not about data privacy but more about the implementation on study sites (50%) and the cost (33%) of such a tool. The site implementation was indeed another important barrier mentioned by the “customer-stakeholders”. However, the cost was evaluated as a hurdle by those in only 12% of the cases.

In a following question, the majority of stakeholders explained that the site implementation wasmore difficult than for a paper-based informed consent (IC) (~61%). In fact, it requires staff training and adaptation and, here again, the fragmented or—in some cases—even lack of regulation around eConsent makes it difficult to implement on sites. However, as one respondent commented, “any change to a normal process is causing difficulties in adapting;” we have to make a first effort if we want to embrace the change and evolution.

Furthermore, this first burden may be worthwhile, as the majority of stakeholders have found that eConsent improves the clinical staff workflow (~70%), facilitates the management of document amendments (~72%), eases the conduct of audits (~80%) and reduces the number of audit findings (~65%). Indeed, the digital aspect of eConsent prevents IC document loss, makes everything available very quickly, facilitates audit trails, and avoids using wrong/old version of the ICF. For the reconsent process, it is also easier to know which patients have not yet consented to the latest version of the ICF. Nevertheless, in order for eConsent to really lighten the workload of sites it needs to be available on multiple devices: vendors’ solutions thus need to be flexible. This will allow the patient to read the information alone and at their own pace, while the staff is busy with other tasks, and to read the information at home, with their family, before deciding whether or not they want to take part in a study.

Another important outcome from the survey was that all stakeholders agreed that eConsent increases the patient understanding of the trial. Indeed, on average, 80% of all stakeholders stated that eConsent allows patients to better understand the trial. Vendor representatives supported this outcome, evaluating the enhanced patient understanding as the most appealing feature of eConsent for customers. This is not surprising as eConsent is first and foremost a patient centric tool. Interactive features and multimedia components like videos and illustrations can be very helpful to simplify and explain difficult information to the patient as shown in the Figure 1 below.

The use of paper-based IC is an important time constraint for the principal investigator (PI) and the site staff who sometimes do not have a lot of time to go properly over the document content with the patient. As one questionnaire respondent noted, with eConsent, “participants will go through the content.”

Among the various eConsent components/features, the ones that apparently have the most impact on this comprehension are the user-friendly interface, visuals, video, and audio. Perhaps these results also indirectly show the reluctance of stakeholders to try new and unknown components and to fully exploit the potential of eConsent.

On the opposite, the components which seems to have the less impact on patient comprehension and engagement are the comment boxes, knowledge assessment and content flags. Indeed, knowledge assessment is considered by many to be too intimidating for study participants. Conversely, according to a Principal Investigator, interviewed for the purpose of this project, asking the participant to answer some questions at the end of the reading/viewing process allows a more pragmatic assessment of the patient's comprehension. The answers to these questions can also be included in a subsequent analysis to identify the overall understanding of the study participants, as well as the IC content section that should be revised to improve understanding. By following the same process, content flags can also be very useful, especially for Sponsors, to identify the "trend" of flags and thus determine which IC section should be modified to provide a better explanation to the participant. Therefore, even though poorly rated, knowledge assessment and content flags can both indirectly help to enhance participant understanding of the study and hence participant engagement in the trial. Those could also constitute proof that all the study participants went through the IC content, understood properly the information, and that all their questions were clarified during their meeting with the clinical staff.

Overall, when asking their opinion on eConsent, all countries were for a broader and global use of this tool, and the majority of stakeholders expressed their growing interest for it following the COVID-19 crisis. On average, 72% of all country representatives were for a broader use of eConsent and 65% of sponsors, CROs, and ISs stated that the recent COVID-19 crisis had increased their interest in this digital tool. They explained that, with the current need for remote visits and speed of starting-up trials, eConsent has become a very attractive solution.

The results from the prospective questionnaire emphasized three important barriers for the implementation of eConsent in clinical trials:

Clinical research experts are missing a dedicated regulatory framework for the implementation and the use eConsent in clinical trials.

People are not educated about the laws and regulations in force and are not educated about the electronic informed consent itself. It appeared in the questionnaire that the inexperienced stakeholders had a less positive opinion towards eConsent, its features, and components.

Indeed, once the people are experienced with eConsent, when it is not an innovation anymore, then the focus is on the processes, the operations and on how to make them as efficient as possible. In the questionnaire, many respondents pointed out the increased difficulty regarding the implementation and day-to-day processes related to the use of eConsent.

Based upon the above findings we can push forward the following recommendations:

The need for a comprehensive, clear and uniform regulation:

A clear legal and regulatory framework for eConsent

Creation of practical and pragmatic guidelines for the implementation of eConsent in clinical trials

Increased continued education and communication:

About the existing and new drafted laws and regulations.

For sites: during the ICH-GCP certification process, an instruction about eConsent and its subtilities might be a good opportunity to educate the sites on this topic.

For ethics committees: training program to educate ECs on eConsent and creation of guidance to standardize the evaluation of eConsent dossier.

Vendors should communicate more about the data protection system and the security of their solution.

Sponsors need to continue to work on lean processes, lean operations to facilitate the implementation and the day-to-day use of eConsent.

Flexibility of Vendors is important: eConsent should be available in several type of devices, simultaneously. In addition, vendors should be able to provide a system to achieve the same "IC amendments" and start-up time as for a paper version of the IC.

Overall, it seems that every clinical research stakeholder has a role to play to truly move the needle of eConsent and increase the implementation of eConsent in CTs.

The prospective questionnaire on eConsent gave interesting insight on the opinions and experiences of eConsent between the three bordering countries as well as between the various stakeholders of clinical research. However, in order to draw more conclusions about eConsent, additional surveys gathering more answers from the three bordering countries but also from the other European Member States would be of great help for the development of a European consortium on eConsent.

, NBCD A/S, Herlev, Denmark & Paris, France, 

, University of Ghent, Heymans Institute for Pharmacology, Ghent, Belgium and Professor, Medical Consultancy B.V. in Heerhugowaard, The Netherlands, 

, Janssen Pharmaceutica NV - Portfolio Delivery Operations, Beerse, Belgium, and 

, University of Namur, Faculty of Medicine, Department of Biomedical Sciences, Namur, Belgium

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Articles

All stakeholders must play part in increasing implementation.

Towards a Global Implementation of eConsent in Clinical Trials

It is increasingly apparent that many physiological and pathological functions as well as patterns in gene expression differ between women and men and gender differences have also manifested in the outcomes of treatments.

 Throughout the last decades, alarming evidence of gender-based differences in the safety profiles of treatments has accumulated. A study including 513,608 patients estimated that women experience a 1.5 to 1.7-time greater risk of developing adverse reactions to drugs than men.

 In 2001, a report from the U.S. General Accounting Office (GAO) made the observation that 70% of drugs withdrawn from the market between 1997 and 2000 presented greater health risks for women.

 On top of that is data suggesting that women are overdosed: the dose of zolpidem, for example, was reduced by 50% in women, after studies showed that women have five times more risk than men of driving impairment after 10 mg of zolpidem.

 Gender differences have also been spotted in effectiveness of treatments: 20 years after the Physician’s Health Study (a clinical trial that excluded women), a large placebo-controlled primary-prevention trial involving 39,876 women demonstrated that daily low dose aspirin has no significant efficacy on the risk of myocardial infarction or death from cardiovascular causes in women, as opposed to results in men.

These differences in the outcomes of treatment can be explained by well-studied gender differences in all the phases of pharmacokinetics

 and the growing literature in pharmacodynamics describing gender differences in drug-receptor affinity, receptor density, or signal transduction pathways.

 Despite these evidences, gender is still is one of the most underappreciated variables in the clinical development of drugs. To address this shortcoming, it is important to clearly define the place of clinical trials in identifying gender differences.

.Since the thalidomide disaster of the 60s, it became a common practice to protect fetuses from clinal trials, rather than protecting them through well controlled clinical studies. In 1977, the FDA excluded “women of child-bearing potential” from Phase I and early Phase II clinical research.

 This 1977 FDA guideline was, however, applied to all pharmaceutical research and the expression “woman of childbearing potential” was defined too extensively as any woman capable of becoming pregnant, regardless of their sexual activity, their use of contraceptives, their sexual orientation, the possible sterility of their partners, or even their desire to have a child. Additionally, several publications indicated that teratogenicity can also be transmitted via sperm.

 This dangerous ban was in application until 1993 and countless drugs were put on the market through clinical research that underrepresented women, exposing (until this day) women to drugs that were not or less tested on them. The FDA 1993 guidance reversed the ban and recommended that clinical studies include men and women “in numbers appropriate to allow the detection of clinically significant gender differences in drug responses.”

This raises several questions: Firstly, what is an appropriate enrollment of women? Gender bias is a complex problem and will not necessarily be solved by the simple achievement of a 50:50 distribution of participants’ gender. Rather than considering only rates of enrollment, a participation to prevalence ratio (PPR) superior to 0.8 is an indicator of appropriate enrollment of women and addresses gender differences in disease prevalence. In the beginning of the new millennium, the GAO suggested that women are “sufficiently represented in clinical trials”

 Regarding late phase clinical trials, Pool et al. estimated in 2009 that the participation of women between 2007 and 2009 was 43.3%, and 3.5% of the clinical trials still unspecify the sex.

 In 2020, Jin et al. revealed that among 740 cardiovascular trials conducted between 2010 and 2017, only 38.2% of participants were women. Furthermore, a participation to prevalence ratio inferior to 0.8 was associated with arrhythmia, coronary heart disease, acute coronary syndrome, and heart failure trials.

Secondly, how early in drug development should enrollment of women be a concern? Pinnow et al. estimate that only 30.6% of Phase I trial participants are women and 34.1% of early trials enroll exclusively men.

 These findings indicate that all the data imminent from early clinical trials, including dose tolerability, dose and use of a drug, the metabolic and pharmacologic data, side effects associated with increasing doses and even the choice of the investigational drug tested in large-scale trials, are mainly tailored based on data from men. Still, is Phase I early enough to worry about avoiding gender bias? Most of our fundamental knowledge of drugs comes from non-human models including animals, tissues, and cell lines, but about 80% of non-clinical studies use only male animals.

 The differences in drug response between female and male animals could forecast the differences in treatment outcomes between women and men patients. In cardiotoxicity studies of dofetilide in rabbit, 100% of female rabbits vs. 30% of males developed severe cardiac arrhythmias and female rabbits developed cardiac arrhythmias at doses 50% lower than those given to males.

 This can be explained by the protective action of testosterone through shortening of the baseline QT intervals.

 Since women are more sensitive to QT interval prolongation than men,

 testing drugs on male-only animals could lead to widely under-estimate cardiotoxicity.

Even if the rate of enrollment of women is appropriate, pooling data of both genders may still yield inexact results and problems of reproducibility. Several theoretical models and clinical trials have demonstrated that pooling data from women and men can mask important male and female differences in baseline data, treatment response and also in sex treatment interactions and leads to biased results that are not adapted to women, nor are they rigorously adapted to men either.

The Digitalis Investigation Group clinical trial is a prime example of the complexity of subgroup analysis. In 1997, the results of the digoxin trial were published, and the outcome was positive. In 2002, Rathore et al. obtained a public-use copy of the data base of the Digitalis Investigation Group and conducted the same study again but performing an analysis based on gender, and the results were alarming. The results for men were identical to the original results, but in women, it was found that digoxin significantly increased mortality and digoxin-associated reduction in the rate of hospitalization for heart failure was smaller.

 The results of this post-hoc analysis were not reproductible in large observational studies.

 When gender-based analysis of randomized controlled trials (RCT) and observational studies are inconsistent, it may raise some confusion. On one hand, post hoc analysis of RCT have less statistical power to detect an interaction between gender and effectiveness of treatment, and even less power to detect interaction between gender and uncommon adverse events and are more prone to type 1 errors (false positive) to detect interaction. On the other hand, observational studies are not randomized, and are biased by unmeasured confounders that affect the interaction analysis. To reduce the weaknesses in the observational design in this regard, propensity-matched analysis reduced the bias due to confounding variables that could be found in an estimate of the treatment effect. To avoid overinterpretation, gender-based analysis must thus be performed but in very strict conditions:

Ensure that there are sufficient numbers of subjects in both gender subgroups.

Provide a rationale for performing the subgroup analysis.

Perform a statistical test of interaction between gender subgroups is necessary but not sufficient.

Adjust p-values for the number of comparisons being made.

Emphasize overall findings: results of gender-based analyses should only be used to produce hypothesis that should be confirmed through post marketing (larger scale) studies.

In 2007, it was reported that among RCT performing a gender-based subgroup analysis, only 35% of studies performed a proper subgroup analysis.

Regarding the sample size, including women and men analysis does not necessarily imply to double of the number of patients to maintain statistical power. More efficient designs, including factorial design (in which two experimental factors with multiple levels are tested, and data are collected across all possible combinations of factors and levels) allow to maintain power at low cost, by increasing the sample size by only 14% to 33%.

In 2020, it is estimated that more than 300,000 clinical trials start every year. This represents therapeutic opportunities but also potential harm for subgroups that are not well represented in clinical trials. In order to be reliable and useful, clinical trials need to be both internally and externally valid. Lack of external validity has created a call for more pragmatic “real life data” trials and the production of data that are applicable to all categories of patients. During this era of personalized medicine, “one-size-fits-all” is not acceptable anymore. Patients need a treatment that is well suited for different subgroups, and women and men are different. Sex is a fundamental variable that should be used to disaggregate data and explain differences in treatments outcomes. To avoid this bias, two main criteria are determinant: inclusion of women in the right number and correct gender-based analysis. In late phase clinical trials, there has been improvement, but men still predominate. In 1993, when the ban of exclusion of women in clinical trials was lifted, one on the main concerns was the underrepresentation of women in cardiovascular trials. In February 2020, the same concern is still raised concerning drug trials on cardiovascular diseases, the leading cause of death. In early phases of clinical trials, women are still largely underrepresented or even excluded, fostering a gender bias in the data of dose tolerability, appropriate dosing, metabolic, and clinical pharmacology. Moreover, when research lacks or excludes female subjects, the guidelines should clearly state that the evidence has been obtained mainly from men. Once a drug is marketed, the scientific or patient leaflet should mention the ratio and total number of women and men that participated in the clinical trials. Regarding analyses by subgroup, it is estimated that only half of clinical trials perform gender-based analysis and only 35% conduct proper subgroup analyses. Investigators should follow guidelines to ensure the proper conduct of subgroup analysis to prevent misleading conclusions from becoming adopted by clinicians. Overall, inclusion of women and gender-based analysis must continue to improve to ensure external validity, reduce gender bias, avoid distrust in controlled clinical trials, and protect women’s health from drugs that are less adapted to them.

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obtained a Master in Biomedical Sciences from the University of Namur, Belgium and

is a Professor of Clinical Trials at the University of Namur, Faculty of Medicine, Department of Biomedical Sciences, Belgium. He is the Honorary President of the Belgian Association of Clinical Research Professionals (BeACRP).

Past decades have shown gender-based differences in clinical trial results are often overlooked when considering safety and effectiveness.  

Gender Bias in the Clinical Evaluation of Drugs

	It is already generally acknowledged that recruitment is one the most important parts of a clinical trial and one of the major reasons for this is that without the appropriate number of patients there is no possible scientifically sound research. However, when literature is reviewed it seems that not reaching initial recruitment targets within initial timelines is more the rule than the exception. This indicates that current recruitment strategies are shortcoming and need to be reviewed. Furthermore, improving recruitment will have scientific, ethical and economic benefits on a global scale.

 defines social media as “the internet and mobile technology based channels of communication in which people share content with each other.” The best-known examples of such social media are social networking sites like Facebook and Twitter. The definition also notes that social media blur the line between producers and consumers-because of the ability to share content between users-and it is in this characteristic that social media is distinct from traditional media channels.

 The evolution of the internet (from Web 1.0 to Web 2.0, allowing websites to run the write and read process at the same time) and the ever increasing internet availability are key drivers in the rise of social media and we are now at a point where social media are a new prime source of information. Furthermore, social media has also created a new way of searching information: instead of actively searching for information, we now use social media to ask for information or we wait for information to reach us via social media. 

	Recruitment exists in essence only of spreading study specific information to potential participants so that they can make an informed decision on whether or not they want to participate. In a way, then it seems logical to investigate whether it is possible to tailor this activity to the new way of searching information. This led to our developing an online survey of social media and the recruitment of study subjects for clinical trials focused on the Belgian clinical trial landscape. For Belgium, improving recruitment will be even more necessary as the country will lose its major advantage of very short ethics committee and Regulatory Authorities approval timelines because of the new European Clinical Trial Regulation. Logically, the country’s strong points--level of expertise, quality of research and number of trials per million habitants--need to be maintained while improving the current weak points.

	The online, cross-sectional survey was conducted to systematically assess the opinions of clinical research professionals from different stakeholders about using social media as a targeting recruitment tool. As the survey was only conducted in Belgium, all questions were specifically about the Belgian clinical trial landscape. The survey consisted of 31 questions, in eight categories, and presented in a fixed way so that every participant completed the same survey. The survey was live between February 3, 2014 and April 20, 2014.

	Invitations to participate were sent to professionals from Clinical Trial Units (CTU), Contract Research Organizations (CRO), sponsors, Ethics Committees (EC) and the authorities (FAMHP). Furthermore, two inclusion criteria were used for inviting participants: they had to be a member of one of the stakeholders mentioned above and they had to be professionally located in Belgium. These inclusion criteria ensured that the invited participants had sufficient knowledge about clinical research and that they were familiar with the Belgian clinical research landscape. Participants from sponsors and CROs also had to be part of a clinical operations/research management team or had to be part of a recruitment department, as this ensured that they had knowledge about trends in the industry and/or trends in recruitment. Potential participants were contacted via e-mail and a standard text was used to reduce bias in the willingness to participate.

	The descriptive nature of the study forced the authors not to define a required sample size up front, as people who participated were deemed to be interested in the topic and/or in developing clinical research and this makes the total number of participants a descriptive statistic on itself. The goal of reaching a number of 120-150 completed surveys was set and completed surveys had to come from members of all stakeholders. The number of completed surveys per stakeholder was however not expected to be equal. Another consequence of the descriptive nature of the study is that statistical analysis is limited and results are presented as mean percentages or as an average numeral score of these mean percentages.

	Of 405 invited professionals invited, 154 participated in the survey, which is a response rate of 38%, and ultimately 135 completed surveys were included in the analysis. This means that 19 surveys were excluded from the analysis, mainly due to incompliance with the survey rules, equalling a drop-out rate of 12%.

	All stakeholders were represented across the 135 analyzed surveys and most of surveys were completed professionals from CTUs (52%). The majority (62%) of these CTU participants were principal- and/or sub-investigators. Almost half of the respondents were professionally located in or around Brussels, which accurately reflects the composition of Belgium. Respondents were almost equally divided in gender and 42% were between 40 and 50 years old. Within this cohort of survey respondents, LinkedIn is the most popular social media platform.

	The majority-81%-of survey participants considers recruitment to be important for the successful conduct of a clinical trial and this reflects the general idea about recruitment. More surprisingly is that 99% of the survey respondents considers recruitment to be a difficulty. The largest part (78%) thinks that it is a difficulty that can be overcome, but a similar portion of the respondents (79%) is still convinced that improving recruitment in Belgium is necessary. Also remarkable is that 82% think that the best way to improve recruitment involves an option that includes developing new recruitment strategies.

	These ciphers indicate that clinical research professionals in Belgium are well aware of the necessity to improve recruitment and they have an open mind toward developing new recruitment strategies. There is, however, a clear distinction between hospital-related research professionals (respondents from CTUs and ECs) and non hospital-related respondents from CROs, sponsors and the FAMHP in the extent on how important recruitment and improving recruitment are to them, with hospital-related thinking of both as less important. Furthermore, the majority of EC respondents believe that improving recruitment can best be done by further developing current strategies, which is opposite of the majority sentiment. From all this information, it can be concluded that the first step toward improving recruitment will be to get all clinical research professionals from all stakeholders looking at improving recruitment in the same way.

	In general, there is a positive attitude toward using social media for recruitment purposes among Belgian clinical research professionals. This can be concluded from the fact that there is always a majority who agrees with one of the following three statements: ‘social media will help in reaching initial recruitment goals within initial timelines,’ ‘potential subjects will be enthusiastic to receive recruitment messages via social media,’ and ‘social media are the best new recruitment strategy of all possible new recruitment strategies.’ The division between hospital-related and non hospital-related respondents is again present. Graph 1 shows that the hospital-related are less convinced that social media will help in reaching initial recruitment goals within initial timelines and the same is true for the two other statements.

	Response per stakeholder + illustration of the relative positive attitude per stakeholder. The relative positive attitude number per stakeholder is the sum of the products of the percentage per answer and the appreciation factor (applied appreciation factors: I strongly disagree = 1, I disagree = 2, I Agree = 3 and I strongly agree = 4). Applying this formula, the minimum relative positive attitude number has a value of 100 while the maximum has a value of 400. The FAMHP is not included in this kind of analysis because of the too small sample size. The average relative positive attitude number for this graph is 263.

	The format of the survey did not allow to assess the absolute use of social media for recruitment purposes and, therefore, we attempted to get an idea of to what extent social media are already used for this cause. The result of this assessment can be viewed in graph 2. The key conclusions from this graph are that social media are already used in Belgium for recruitment purposes and the most stated reason for rejecting social media recruitment strategies is ethical/privacy concerns.

	The percentage of the parameter ‘respondents’ is given in function of the total number of individual participants included in the analysis (n = 135). The percentages for the parameters ‘yes’ and no’ are given in function of the number of individual responses per question (n = 106, n = 101 and n = 102 respectively).

	Even more important than the result regarding the actual use of social media for recruitment purposes, are the results regarding the ideas about the future use of social media for recruitment purposes. Forty percent of the participants think that social media are already used for recruitment purposes but 87% think that they will be used to recruit study subjects within the next 10 years. This percentage even augments to 90% when participants were asked if social media would ever be used for recruitment purposes. This indicates that Belgian professionals think it is inevitable that social media will be used as recruitment tool in the near future, which corresponds to a generally positive attitude towards social media recruitment and developing new recruitment strategies . It also points out that efforts should be done to make clinical research ready for the introduction of social media.

	A general trend among people involved in clinical research is that they expect problems with implementing or using social media for recruitment purposes, reflected by the 67% who think that CTUs do not have the knowledge to perform a social media recruitment campaign. This belief is justified, as 73% of CTU respondents stated that they do not have the knowledge to do so. Furthermore, 78% is also convinced that the current regulations and guidelines regarding recruitment aren’t sufficient to regulate the use of social media for recruitment purposes. Next to these structural problems, there also seems to be some ethical concern as there is a 21% difference (83% versus 62% respectively) between respondents who consider it acceptable to recruit healthy volunteers with social media and respondents who consider it acceptable to recruit patients with social media. Also remarkable is that hospital-related CRPs have greater concerns about ethical and privacy issues compared to not hospital-related CRPs. However, from comparing graphs 3 and 4 with graphs 5 and 6, it can be concluded there is a greater concern about the structural problems. It is also notable that this is the case for each stakeholder group.

	Comparison between the relative positive attitude numbers per stakeholder for the statements written with each graph. The mean relative positive attitude numbers are 233, 212, 307 and 271 respectively. These indicate that there is a less positive attitude towards the structural problems (graphs 3 and 4) and that there is a more positive attitude towards recruiting healthy volunteers with social media compared to recruiting patients (graphs 5 and 6).

	Also important to point out is that almost half of the respondents (47%) believe that ECs will be the greatest barrier to the implementation of social media into the recruitment process. Respondents from EC seem to understand that they could be a barrier, as a quarter pointed themselves out as the greatest barrier. A majority of the EC respondents, however, point toward the organizations (Belgian Council of Medical Doctors (30%) and the FAMHP (25%)) that create the guidelines and regulations they have to take into account when forming an opinion as the greatest barrier. This indicates again that the current regulations and guidelines are a major obstacle to implementing social media recruitment and that a thorough review is necessary before advanced recruitment tools, like social media, can be used in a safe and ethical way.

	The paragraphs above give an overview of the ideas of Belgian clinical research professionals about social media recruitment but these ideas and doubts aren’t necessarily correct or justified. Sixteen percent of the survey respondents indicated that they already did research on social media recruitment and half of these respondents belong to a CTU. In order to check whether these respondents actually did research on social media recruitment some general control questions about social media were included in the survey. The result of this is illustrated in graph 7 and confirms that the ‘have done research’ group has a better social media knowledge than the ‘haven’t done research’ group.

	Comparison between the ‘have done research subgroup’ and the ‘haven’t done research subgroup’ for the control questions on social media knowledge. These control questions were based on general statements found in social media literature. The ‘have done research’ subgroup gives answers that are in better agreement with what is found in literature.

	Over the whole result of the survey, the ‘have done research’ group is more positive about social media recruitment and also gives-according to what was found in literature-more correct answers about it. This is confirmed by the relative positive attitude analysis, visualized in graph 8. It can thus be concluded that any reluctance or misjudgment towards social media recruitment is mainly the product of a lack of knowledge. The ‘have done research’ group also has less ethical or privacy concerns and shows for example only a marginal difference between their opinions on the acceptability of recruiting patients or healthy volunteers via social media. This indicates that privacy and/or ethical concerns are really not a major problem of social media recruitment and this collides with the fact that the most stated reason for rejecting social media recruitment tactics are privacy/ethical concerns. The opinion of this group about the structural problems does not differ a lot from the ‘haven’t done research’ group, which confirms that these problems are indeed the greatest barriers to the implementation of social media into the recruitment process.

	Comparison between the ‘have done research subgroup’ and the ‘haven’t done research subgroup’ for the survey statements on the problems with social media recruitment.

	From this research, it can be concluded that patient recruitment should be improved and that this certainly applies to the Belgian clinical research landscape. Via a literature study and this survey, it was assessed that social media is a promising tool to enhance recruitment. It can be used as a targeting recruitment tool but also as a medium to create more knowledge and awareness about clinical research. The latter is a new major responsibility of the pharmaceutical/clinical research industry that can best be done by providing correct, understandable and patient-centric information via the patients’ new information sources, like social media. Interaction between the industry and patients via these media channels is also something to be considered.

	The survey pointed out that Belgian clinical research professionals from different stakeholders believe that social media can help in improving recruitment and that they expect that social media will be used in the near future to recruit patients. The major obstacles that are withholding us from recruiting patients via social media are a lack of knowledge on the matter and an insufficiency of the current regulations and guidelines about the use of social media in clinical trials. Ethical and privacy issues seem not to be of great concern.

Vincent Schroyens, Quintiles Belgium – Department Site Management; Jessica Van Den Broeck, Quintiles Belgium – Department Site Management; Yves Geysels, Quintiles Belgium – Department  Site Management, University of Namur – Faculty of Medicine: department Biomedical Sciences

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A survey of Belgian clinical research professionals offers insights into the future of social media

Yves Geysels

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