12.2.1 Participant’s low literacy and form’s length

According to mainstream discussions of the consent process, full disclosure of medical information through traditional consent forms remains a challenge because of the complex medical concepts being communicated coupled with low literacy rates among American adults.^[7] The current average reading literacy among American adults is at the eighth grade level.^[10] Notably, 75% of adults with long-term illnesses also fall below this national average.^[11] So, medical researchers are assigned with a difficult task of communicating complex information to populations with significant barriers to comprehension.

In a review of the informed consent templates of 114 medical IRB, researchers found that most templates were written at an average of the tenth grade level. This average is approximately three grades above the IRB’s self-recommended standard. ^[7] This disparity between consent forms and literacy levels of potential study participants has fueled a growing body of research suggesting that participants frequently do not comprehend consent information. For example, one study reported that 70% of participants in an oncological clinical trial did not know that the experimental treatment had not been proven to be effective, and 25% did not know that the trial findings would mostly benefit future patients, not study participants.^[12] Even in a clinical trial that largely enrolled participants with college-level educations, only 12% of participants (n = 82) could name the three trial drugs and only 17% could recall three or more out of 23 possible risks.^[13]

A recent study found that the length of US and international consent forms for NIH-sponsored HIV trials were an average of 22 pages, which exceeded recommendations for how much information could be reasonably processed.^[14] The authors suggested highlighting key information to enhance the reading process, but also noted the ethical dilemma of identifying the appropriate information to highlight. Additionally, a study evaluating how different stakeholders value information on a consent form found that the IRB officials identified most of the form as important (72 % of the sentences). But in a telling contrast, participants thought that less than half of the form was vital (40% of the sentences).^[6] Importantly, informed consent forms have also been described by patients as symbolic rituals for protecting medical doctors and institutions rather than vehicles for ensuring patient autonomy.^[15] Therefore, not only are medical consent forms lengthy and difficult to understand, but a discrepancy exists between what different stakeholders perceive to be the true objective of the form and the way they distinguish meaningful and necessary information.

12.2.2 Participant’s desire to have more control over what is shared

Recent studies suggest that subjects want more granular control over how their clinical data is shared for research. It seems that subjects’ attitudes toward sharing information for research could be influenced by multiple factors:^[16]

1. Type of information: subjects are less willing to share information that becomes more personal, for instance sensitive information related to drug abuse, sexual-related diseases, etc.^[16]
2. The identity of the recipient of the information: support for sharing medical record data decreases when suggested users included commercial, for-profit recipients.^{[17], [18]}
3. Level of anonymity: subjects have privacy concerns and are more prepared to share anonymous information.^[19]
4. Demographics of the subject: subjects with chronic or progressive illnesses seem to be more willing to share.^{[17], [20]}
5. Perceived value: the emergence of highly active virtual research communities of persons affected by similar conditions seems to be based on subjects’ perceived value of peer-based sharing models and their hopes of accelerating the prevention, treatment and cure of those conditions.^[21]

Though better understanding of attitudes and willingness to engage in public health research is needed, the mentioned studies suggest that the use of broad consent models should be rethought to favor tiered consent models that provide subjects greater choice in information sharing. Furthermore, support for the idea of giving patients granular control is also encouraged by the U.S. Office of the National Coordinator for Health Information Technology, which indicated that patients should have a “greater degree of choice to determine, at a granular level, which personal health information should be shared with whom, and for what purpose”.^[22]

12.2.3 Participant’s interest to know research results

There is an open debate on the scope and limits of investigators’ responsibilities on sharing research results. Some advocate for routinely offering results to research participants, ^{[23], [24]} and there are national and international policies and guidelines on the duty to return results.^[25] Furthermore, the review by Shalowitz and Miller has shown that of studies that reported desire to receive results as a percentage of respondents, a median of 90% (range 20%–100%) wished to receive study results.^[26] In addition, it was reported that those who were responsible for clinical trials considered it was important to return those results.^[26] Nevertheless, it has been reported that clinical trial participants are often not offered the option of receiving the trial results, or are not provided those results when offered,^[27] though there is evidence that the process of preparing and disseminating clinical trial results could be feasible and executable.^[28] To address the problem that clinical trial participants are not offered access to trial results, in 2011, the U.S. FDA required informed consent forms to include a statement informing the participants that the results of the trial will be uploaded in the ClinicalTrials.gov registry. While the adoption of the registry significantly increased the number of returned trial results,^[29] it did not help to address the problem of facilitating participant’s access to those results.^[30] Even if the subjects were able to access to the registry and found the results returned by the trial they participated in, they could not necessarily interpret and understand those results. While the registry links clinical trials with associated scientific publications, those publications are meant for the scientific community and therefore cannot be easily understood by the subjects.

By not disclosing results in ways that are meaningful for the trial participants, the research community could be losing the opportunity to build trust with participants.

12.2.4 Attitudes of both medical researchers and participants toward informed consent processes

A study in Austria interviewed stakeholders of a bio-repository study that collected human tissue for research in an effort to take into account broader factors that influenced patient decisions. They found that medical researchers viewed informed consent primarily as a process to secure legal research rather than an issue of assuring patients’ freedom of choice.^[15] Comparatively, researchers who also entertained ethically ideal concepts of patient autonomy appeared to justify perfunctory consents by holding to assumptions that patients were not willing to receive in-depth information: “Often…it [the information] challenges patients very much intellectually. Why should they be interested in something that doesn’t really interest them… 10, 15 pages, no patient wants to read that, definitely not [sic.]“.(p. 94)^[15]

In the same study by Felt and colleagues (2009), patients were interviewed following consent procedures. Researchers found that many patients had low interest in learning from the consent process because they were more interested in broader notions of contributing to medical innovation than the study directly at hand. Some patients also avoided asking extra questions about the study because they were concerned about putting further demands on their medical provider or that refusing a study could cause conflict and complicate their medical care. Another study examining patient preferences for autonomy found that, although they wanted to be informed, patients preferred medical decisions to be made primarily by their medical providers, especially as the severity of the illness increased.^[31] Such findings demonstrate how informed consent goes beyond the scope of providing accurate and comprehensible information but also delves into realms of social obligation and influence.

12.2.5 Patient autonomy and social forces of influences

The informed consent process for medical research is not normatively accepted as a persuasive process in medical literature but as a method for ensuring patient autonomy and understanding of pertinent study features.^{[32], [15]} Indeed, the Belmont Report clearly states, “Informed consent requires conditions free of coercion and undue influence” (Part C, paragraph 11).^[4] However, it later brings to light a paradoxical issue by noting that “unjustifiable pressures usually occur when persons in positions of authority or commanding influence – especially where possible sanctions are involved – urge a course of action for a subject” (Part C, paragraph 12). This is a paradoxical issue because medical experts exercise significant influence de facto as they habitually care for and enroll people in vulnerable states.^{[32], [15]} Consequently, persuasive forces are inherent to the informed consent process as Felt et al. (2009) aptly described: “power relationships between medical practitioners and patients lead to unequal encounters wherein personal autonomy cannot be realized in the way it is imagined by the dominant bioethical ideal”. (p. 89)

The following discussion further demonstrates how “coercion” and “undue influence” are difficult concepts to define and may be overlooked when consent procedures are examined through the broader context of medical research and recruitment. ^[15] For example, this statement by a medical investigator interviewed in a qualitative examination of consent processes demonstrates how recruitment and consent communication are not only intentional but also framed to elicit more favorable attitudes: “You want to actively recruit people for a study, which means that you make things attractive. You don’t stand there and tell them that it might be dangerous for them. Then, maybe, you wouldn’t find anybody.” (p. 94)^[15] This statement does not represent the views of all medical researchers, but it brings to light the fundamental motivation for researchers to employ persuasive strategies in order to actively recruit participants and to move medical investigations forward.

Moreover, for persuasion to take place, message recipients must be free to adopt attitudes and behaviors that are contrary to the advocated positions.^{[33], [34]} Otherwise, the change in attitude cannot be attributed to persuasive appeals of the communication. Nevertheless, no one is truly free of influence by virtue of the social nature of humanity. For example, a medical student was asked to reflect on the issue of freedom of choice and a patient’s ability to refuse a physician. The student stated, “You won’t refuse a request from somebody who is helping you”.(p. 94)^[15] Inadvertently, the student touched on a critical force of social influence. Indeed, Robert Cialdini (1984), an eminent scholar in persuasion research, expounds that mutual exchange or reciprocity is a fundamental driver of human behavior that defies all social and cultural boundaries.^[35] Essentially, people are “programmed” to feel obligated to return favors. Thus, patients may feel obligated to join medical studies for helpful medical practitioners that they otherwise would not. Such instances are not necessarily problematic , but it shows how the “atmosphere of free choice” is difficult to construe and actualize in the research recruitment context and should be taken into consideration in effective informed consent processes.

12.3.1 Participant’s low literacy and form’s length

Beyond recall-testing interventions for informed consent, several approaches for improving comprehension of consent materials have been investigated in the literature. Improving the readability and length of forms – a popular approach – has been shown to significantly boost comprehension of consent information.^[36] Readability refers to how easily consent forms could be read, and it is intentionally enhanced by using simpler words, writing in active voice and organizing the form in a more appealing manner (i.e. using bullets, increasing white space, etc.). Simply adding pictures to spoken instructions has also been shown to improve recall of medical information. ^[37] Moreover, a large body of research supports the usefulness of multimedia for enhancing comprehension; however, its adoption rate appears to be hampered by its involving development process.^{[38], [39]} Despite the existence of these helpful strategies to improve comprehension, a 2004 systematic review of consent interventions determined that the most effective way to secure consent was to continue using face-to-face discussion between neutral educators and participants.^[8] Therefore, consent interventions including electronic systems, eConsents and multimedia should be viewed as complimentary components to the human-mediated consent process rather than a stand-alone program.

12.3.2 Participant’s desire to have more control over what is shared

Medical records provide a rich source of information for advancing clinical care through research, particularly with the advent of electronic health records (EHR).^[40] As a result, secondary use of EHR for health outcomes research has become prevalent. However, patient control over sharing of their personal medical records is rare. Many healthcare organizations use broad consent forms for future research involving a patient’s medical data. Biological specimens extracted from patients during clinical care also provide an important resource for research especially in the genomic era. However, the use of these specimens for research requires explicit consent from research participants.

The University of California San Diego (UCSD) has developed a tool called iCONS (informed CONsent for clinical records and Sample use in research) that allows for inclusion of educational materials in informed consent documents by using an electronic consent form. This form is web-browser compatible and can be used on tablet computers. This tool was built for a study at the Moores Cancer Center for patients who were consenting to donate biosamples and clinical data to the biorepository. In the tool, patients can view the regular content of the consent form as well as additional multimedia resources that were designed to offer more information. Besides, UCSD has developed a Permission Ontology that allows expressing subject’s consent permissions in a precise and uniform formalism that supports machine-based reasoning. ^[41] This Permission Ontology could be linked to the iCONS system to capture participant’s choices on sharing data and biosamples during the informed consent process. Furthermore, in order to be able to maximize researchers’ access to clinical data and biosamples obtained through informed consent and available at Moores Cancer Center Biorepository, UCSD has built a Resource Locator prototype.^[42] The Resource Locator prototype accesses repositories of consent permissions expressed in the Permission Ontology and determine if researchers’ request for resources from the biorepository could be granted in compliance with subjects’ permissions.

Figure 1: Screenshot of the iCONCUR tool, being developed by the University of California, San Diego

In addition, UCSD is currently developing an online tool called iCONCUR (informed CONsent for clinical data use for research) that uses taxonomies of choices to give patients control over how the information in their medical record is shared for research. Patients can decide what to share and with whom. For instance, a patient wants to share all the clinical information with non-profit researchers, but only diagnostic data with for-profit organizations. The tool will be used in a two-year clinical trial. During the duration of the study, the UCSD Clinical Data Warehouse will honor participants’ choices when sharing clinical data for research.

Other academic medical centers have developed and piloted electronic consent systems.^{[43] [44] [45]} At the Medical University of South Carolina (MUSC), a home-grown electronic system for capturing permissions related to research was piloted over a 12-month period. For example, patients could opt out of being contacted for research during the review of the electronic consent during patient registration on a tablet device. MUSC is exploring the use of a new version of this system for informed consent for participation in clinical trials.

Commercial approaches have been developed too to make it safe for individuals to allow granular control over their confidential information, such as personal medical records, and to share that information over the internet. For instance, this is the case of Private Access Inc. Through their web-based application, “[…] patients are able to make their information available to trusted researchers or research groups, and to decide who should have the ability to search and view this information on the basis of anonymous or personally identifiable records. Once established, these private access rights open the ability for researchers to locate patients who match their particular criteria and to inform these patients of clinical trials that may be of interest.” A patient’s expressed permission is required to release highly granular data and personal contact information.

12.3.3 Participant’s interest to know research results

With internet access being widespread, patients have more opportunities than ever to share information about medical procedures, pharmaceutical drugs and research studies. Health-related forums give a chance to review doctors or medicines, find others suffering from the same disease and lend moral support. This patient-centered approach uses social media and personal communication to disseminate information, unlike more traditional organization-centered approaches of publishing data and presenting to peers at conferences.^[21]

One example of a patient-centered approach is 23andme.com. This company gives the opportunity for an evaluation of your DNA for $99. Results are presented in such way as to highlight ancestry, potential risks for diseases and physical traits such as hair color. Participants who elect to give DNA sample also consent to have their genetic information used for research studies. Comparisons with peers through the web portal 23andme.com allow for dissemination of results to others who have similar results or shared ancestry.

Another example is PatientsLikeMe (http://www.patientslikeme.com/) which is an online patient network that allows subjects to connect with others with similar medical conditions (from prevalent conditions like diabetes, to rare conditions like ALS) to share experiences, learn, support others and contribute to research. As it is stated in their website: “The value of this open, community-driven approach to healthcare research was first demonstrated in 2011, when PatientsLikeMe revealed the results of a patient-initiated observational study refuting a 2008 publication that claimed lithium carbonate could slow the progression of ALS. The study, published in the scientific journal Nature Biotechnology, marked the first time a peer-to-peer network was used to evaluate a treatment in a patient population in real time. It was the first of a number of patient-reported outcome studies that have increased our understanding of diseases.”

Companies like 23andMe, PatientsLikeMe and other research networks^{[21], [46]} seem to be filling subjects’ need to be more involved and informed on research studies, while strengthening the trust of subjects on research. They perform research that could be relevant for the subject, publish and share the results with the scientific community and explain the research results to the members of the research network in an easy-to-understand way.

12.3.4 Online health information and its implications for patient autonomy

The Web 2.0 has transformed the way people process and formulate health attitudes in a way that could help enhance informed consent. Web 2.0 refers to the newly evolved way to use the internet platform “where content and applications are not created and published by individuals, but instead are continuously modified by all users in participatory and collaborative fashion”.(p. 61)^[47] Consequently, according to Pew Internet’s 2010 Internet and American Life Project Survey, 80% of internet users look for health information online, making it the third most popular online activity.^[48] Although most individuals continue to prefer receiving health information from their healthcare providers, a growing number of people are actively seeking health information online and other laypeople or online users.^[49] Indeed, 60% of the online health information seekers discussed in the Pew report claimed that their discoveries had some influence on their health decision.

With unrestricted numbers of people creating and sharing content online, the consequence of excess information appearing on the Web is inevitable. This deluge of information has led people to employ different strategies for filtering through meaningful information. One way for people to retrieve meaningful information is by relying on other users and consensus heuristics, such as the belief that “the truth lies in numbers”. In assessing how individuals search for and appraise health information online, Eysenbach and Kohler (2002) found that despite participant claims that they critically evaluate online health information, they instead bypassed these assessments and relied on search engine rankings to retrieve health information.^[50] People’s preference for information recommended by search engine rankings over other expert sources has also been demonstrated in other studies.[51] Search engines are presumably credible because they are promoted by the collective “others” and their collective intelligence.^{[47], [51]}

Another decision tool that employs consensus heuristics is consumer ranking systems. According to Pew Internet’s 2009 report discussing the social characteristics of online health information:

• – 24% of e-patients have consulted rankings or reviews online for doctors or other providers;
• – 24% of e-patients have consulted rankings or reviews online of hospitals or other medical facilities.(p. 3)^[49]

Little is known about how individuals process rankings or reviews of medical information; however, evidence from consumer research provides valuable insights into how they influence decisions. For example, consumer review systems are becoming increasingly popular thanks to Web 2.0. Although there is no standard model, consumer rating systems generally take in user feedback to generate various symbols intended to communicate a specified item’s level of popularity.^[52] Examples of consumer rating systems include Amazon.com’s customer reviews, which allow consumers to rate products and sellers, and Kindle’s Popular Phrases application, which underlines phrases that have been highlighted most frequently by other Kindle users, along with the number of people who highlighted each phrase (see Figure 2).

According to current findings in consumer research, user ratings significantly influence behavioral intentions. This was best highlighted in an experimental study investigating the influence of online reviews on customer purchase intentions, Park, Lee and Han (2007), which demonstrated that the quality and number of reviews have a direct relationship to consumer purchase intentions.^[53] Participants in the group with a low number of poor-quality reviews demonstrated the least intentions to purchase. In contrast, the group with a high number of high-quality reviews demonstrated the highest intentions to purchase. Most importantly, the number of reviews, regardless of their quality, significantly predicted purchase intentions and perceived trustworthiness of the reviews. Similar studies by both Chevalier and Mayzlin (2006) looking at consumer ratings and book sales, and Zhang and Dellarocas (2006) looking at the movie industry, have obtained similar results.^{[54], [55]} This reliance upon customer reviews comes with an important caveat: there are reports of user reviews being commissioned by companies so some perceived “others” may be commercial sources, not similar individuals.^{[56], [57]} The manipulative nature of these practices is underscored by the fact that current literature suggests that consumers prefer user-generated reviews to seller reviews because they are less biased, more credible and are consumer-centered.^{[58], [59]}

Figure 2: Consumer rating systems: (a) customer reviews from Amazon.com; (b) Kindle’s Popular Phrases application.

In summary, Web 2.0 technologies and associated new ways of thought about information-sharing and meaning-making may suggest a solution to the issue of securing informed consent, especially to help alleviate or counteract the power imbalance between healthcare providers and patients. Specifically, participants could figuratively construct road signs on existing consent forms to filter through meaningful information while also preserving the breadth of information that is necessary to consent forms. Indeed, an experimental study by Schneider (2013) revealed that participants given an informed consent form that was highlighted by patients were significantly more likely to expend greater effort in processing the overall consent form than participants who were given an informed consent form that was highlighted by researchers.^[60]