Purpose: Regulatory authorities and health care practitioners participating in international clinical trials are often discussed in the technical writing literature. However, the most vulnerable audience—the participants—is left out of the conversation. The purpose of this article is to examine the influence of legal and cultural contexts on participant-directed informed consent documentation. Such examination will help technical communicators make informed consent documentation more user-centered.
Method: Using excerpts from informed consents that I translated into Russian, examples from my six years as a localization specialist, and an overview of contradictory U.S., Russian, and international laws, I analyze the legal, ethical, and cultural considerations for informed consent documentation in international clinical trials.
Results: The results of this analysis show that international regulations often differ from U.S. and Russian laws. In addition, the culture and way of life in the country where a clinical trial originates (e.g., the United States) might differ from those in the country where the trials are conducted (e.g., Russia). These differences influence the comprehension of information in informed consent documentation and a patient’s decision to take part in a clinical trial. Technical communicators are often responsible for the difficult task of reconciling the contradictory issues raised in international clinical trial legislation, differences in legal systems of particular countries, and tensions between law and culture.
Conclusion: I offer strategies that technical communicators can adapt to work in the best interests of their audience and to present user-centered information in informed consent documentation.
Keywords: international clinical trial, informed consent, user-centered design, audience, international regulations, law and culture
- It is important to determine early in the project’s lifecycle whether an informed consent document will be used abroad. If the document is intended for translation, localization specialists can help analyze your audience and can become a reference source (e.g., on international laws).
- It is essential to explain or provide references for all concepts and terms (even the term “clinical trial”) and to individualize the content and design of each informed consent document (e.g., by providing space for additional information or developing comprehension checks).
- It is of paramount importance to use consistent, unambiguous terminology and to avoid the connotation of “treatment.”
Introduction: Culture Meets Law
Bonk (1998) states that technical writers who design documentation for regulatory agencies and health care practitioners in the global pharmaceutical industry experience legal and ethical pressures, as they can be responsible for social benefits and serious harm. These pressures result partially from the requirement to have a working knowledge of both U.S. and international law. In creating informed consent documents for international clinical trials, technical writers must address authorities from multiple countries and coordinate their legal requirements so the study can be authorized in the country where the trials are conducted and the results will be accepted in the country where the medication was invented.
However, legal pressures and the strains of the market often cause technical writers to overlook the audience whose safety should be the primary concern: the participants in clinical trials. Indeed, job descriptions on various Web sites for technical writers mention assisting “with the development of the informed consent … in conjunction with the clinical trial team”; writing “investigational drug brochures” (www.greenkeyllc.com); and preparing “Informed Consent Forms [and] patient narratives” (www.inventivclinical.com). Technical writers are required to have a “solid understanding and experience with application of GCP [Good Clinical Practices]” (Green Key Resources). They need “knowledge of FDA [U.S. Food and Drug Administration] regulatory requirements and ICH [International Conference on Harmonization] guidelines” (inVentive Clinical) and experience with “AMA [American Medical Association] writing guidelines” to help “change the lives of people around the world” (Baxter International Inc.).
None of the job ads mention anything about understanding the needs of study participants; this omission can result in documents that show no concern for their audience. The problem becomes especially obvious when informed consent documents are offered to patients who are not fully aware of their illness. Such situations are not uncommon in cultures in which families play an active role in directing health care for their members. While working as a medical interpreter in a Midwestern hospital, I witnessed such a situation. When I interpreted the results of medical tests to an elderly Russian-speaking patient in the Emergency Room, his bilingual children and wife broke down in tears and tried to convince me to let their father/husband “die in peace.” The family had been aware of the man’s disease for several years but had never told him about the full extent of it. In Russia, this was possible because of the leniency of the law in such dramatic and emotional situations, where not telling the patient is considered ethical and kind. In this situation, when the doctor and I tried to explain that it was the patient’s right to know about his condition, the family pointed out the cruelty of the law. However, when the doctor mentioned that there was an experimental medication for the condition and that the patient could take part in the study of this medication, the family stopped interfering with our efforts.
The doctor offered to provide more information about the study to the patient and brought the informed consent brochure. The document fulfilled the right of the patient, determined by U.S. law, to receive information. In this case, it provided facts about an experimental medication for an incurable disease to a patient who did not know that he had this disease in the first place. Technical writers need to be aware of this context and focus on the various potential audiences to shed light on how legal requirements for international clinical trials intertwine with participants’ determination to put themselves at risk of adverse effects for a chance to regain their health or for the greater good. Since such vital decisions are often nested in the cultural background of participants, technical writers need to follow the suggestion of Kim, Young, Neimeyer, Baker, and Barfield (2008) to study “cultural differences in decision making” and “notions of patient rights and agency” (p. 352).
To address this problem, I begin with a brief overview of the informed consent process in clinical trials and the concerns regarding the documents used in the process. I explain why offshoring clinical trials (to the Russian Federation in particular) is becoming increasingly popular. With an increase in the number of offshored clinical trials comes an increase in the clinical trial documents that must be translated into foreign languages. Meanwhile, some factors that encourage offshoring (and thus the growth of the clinical trial translation industry) can be detrimental to the rights of the participants. Awareness of these contradictions is paramount for technical writers, as it gives them the power to withstand legal and ethical pressures and to direct their efforts to protecting the best interests of the participants.
I use the United States and Russia as examples to look at current legal issues in international clinical trials and at how national and international law, ethics, culture, and traditions clash when they interact in the creation of one of the most important documents in clinical trials, the informed consent brochure. Using examples from actual informed consent documents I have translated from English into Russian, I make recommendations that will help technical writers withstand legal pressures, acquire more knowledge about the participants of clinical trials, and create informed consent documents that take the interests of participants into account.
Informed Consent Documentation and the Interests of Participants
According to the FDA, a clinical trial is a research study that is “used to determine whether new drugs or treatments are both safe and effective”; it is “the fastest and safest way to find treatments that work in people” (Clinical Trial entry in the http://www.clinicaltrials.gov glossary). The full definition emphasizes that the trials start with small groups of people and expand to very large groups to allow for sufficient comparative analysis. It is the primary task of legal regulations to ensure that the studies are safe and fair to these groups.
One prerequisite for safety and fairness of a clinical trial is the participants’ knowledge of what the trial entails. The most common way to convey such information to patients is through an informed consent brochure, which describes the goal, duration, and required procedures of the trial; provides contact information for study investigators; and explains the rights of participants and the risks/benefits of participation. When participants sign an informed consent form, they confirm that they have received sufficient information about the trial and state their wish to be part of it. Because the informed consent form is not a contract, participants can decide to withdraw at any time (http://www.clinicaltrials.gov).
Clinical trials entail a “stronger professional duty to communicate information about risks in the context of research than in the course of normal clinical care” (Hall, 2000, p. 291). Since the task of a trial is to determine the safety and efficacy of medication, the probability exists that an experimental drug could have no benefit for the health of a patient or could even cause harm (e.g., incorrect dosage, unforeseen side effects). In addition, many trials are placebo-controlled, which means that a patient might unknowingly be one of the participants who receive a sugar pill. All this information must be conveyed during the informed consent procedure, and informational brochures are a primary source of knowledge. Clinical trials encourage discussion between doctors and patients; the consent forms protect patient autonomy and well-being. Ideally, the primary purpose of informed consent documentation is “to promote the goals of informed consent, rather than merely serve as documentation and thus liability protection” (Berg, Appelbaum, Lidz, & Parker, 2001, p. 190).
However, both scholars and practitioners have criticized informed consent documents in the United States for a number of reasons:
- Informed consent documents are often equated with informed consent procedures. Doctors rely on these documents as the only source of patient education and view the signature as a sign that the patient is well-informed about all the implications of the study. “With informed consent having its roots in the law, it is not surprising that the idea was implemented through legalistic approaches,” and the pursuit of the autonomy and well-being of the patient has “achieved an ethics in practice that revolves around the signing and filing of pieces of paper” (Smith, 1996, pp. 179, 184).
- These documents do not “appropriately inform and empower the participant, because the information in the consent document increasingly serves institutional rather than participant needs. … Consent forms have been hijacked as ‘disclosure documents’ for the risk management purposes of research organizations” (Federman, Hannam, & Lyman Rodriguez, 2003, p. 93).
- Informed consent documents fail to prevent “therapeutic misconception,” a situation in which participants of clinical trials do not differentiate between research and treatment and, as a result, overestimate the nature and likelihood of study benefits (Appelbaum, 2002; Horng & Grady, 2003; Moreno, 2003). King et al. (2005) analyzed consent forms from early-phase trials to examine how “consent form language might promote or reduce the therapeutic misconception” and concluded that consent forms are often vague, inconsistent and overstated, “which may promote confusion about what subjects can expect from receiving the experimental intervention” (p. 5).
- They do not provide space for patient questions, doctor-patient discussion, and additional information disclosed as a result of these interactions. At the same time, they can be so long that they lead to information overload.
- They are used as a formality. Patients should be able to take these forms home to carefully read them and discuss them with their families. However, the forms are often handed out during doctor-patient discussions, allowing patients only a few minutes to look them over (Morrow, Gootnick, & Schmale, 1978).
- They display a disregard for the linguistically and culturally defined understanding of information. A patient might have a different concept of a certain disease than the doctor has (e.g., a patient may believe that she does not have cancer because cancer patients are usually sick and lose weight, while the doctor has medical proof of the diagnosis) or might have no conceptual base to understand medical concepts (Faden & Beauchamp, 1986).
Awareness of these factors can help technical writers create participant-centered documents and assist them in their ethical task of protecting the interests of participants of clinical trials. These criticisms also emphasize the need for improvement in the design of informed consent documents. When such documents are translated into other languages, the situation becomes even more complicated, as the clinical trial now involves several cultures. Over the past six years, I worked on a large number of informed consent documents for clinical trials that started in the United States and continued in other countries. In these trials, informed consent documents written by American technical writers were translated and used abroad, thus transferring all the existing problems of the documents into an international arena.
Offshoring Clinical Trials: Benefits and Contradictions
The number of clinical trial documents translated from American English into foreign languages is increasing every year; in the past decade, offshoring has become a trend among U.S. pharmaceutical companies. The number of investigators who base their studies on FDA regulations and work outside the United States has grown by 15% annually, while the number working in the United States has decreased by 5.5% each year (Getz, 2007). Glickman et al. (2009) reviewed trial recruitment for the 20 largest U.S.-based pharmaceutical companies and determined that the majority of study sites were outside the United States, and about one-third of all the trials did not even start in this country but was rather conducted only abroad. Many of the trials they examined were conducted in the rapidly evolving countries of Eastern Europe and the Russian Federation.
Economic Reasons for Offshoring
The reasons for offshoring clinical trials are many, but cost savings is the most obvious. One case report showed, for example, that a first-rate academic medical center in India charges $1,500 to $2,000 per patient case report, whereas a second-tier center in the United States would charge 10 times more (Garnier, 2008). In addition, involving international participants allows companies to shorten the trial time.
Since trial sites in North America usually have multiple ongoing studies, the competition for participants is fierce; at the same time, once the experimental drug is patented, its producer has exclusive rights for only a certain period. These so-called “time costs” account for approximately half the price of getting a new drug approved in the United States (Lustgarten, 2005). According to International Conference on Harmonization Good Clinical Practice (ICH-GCP) standards, which are followed by the FDA, new participants can be added later in the study; by recruiting participants in developing countries, sponsors and investigators can speed up the trials.
Furthermore, owing to the large number of ongoing studies and the increase in enrollment criteria, it has become very hard in the United States to recruit participants for clinical studies, and fewer participants finish the trials than in other countries (Malakoff, 2008). Offering payment to participants of clinical trials is equally unacceptable throughout the world; still, it is easier to recruit patients in developing countries (Lustgarten, 2005).
Medical and Legal Reasons for Offshoring
Patients in developing countries typically are “naïve.” Previous treatment may confound the results of clinical studies, but naïve patients have not received care for their diseases and conditions (Mitchell, 2008). In addition, the large pool of recruitable subjects in many developing countries offers many genome variations and allows the investigators to study different ethnic responses to the experimental drugs. The FDA urges that clinical studies be conducted on ethnically diverse populations, since such testing can provide an understanding of how medications affect various groups. In fact, if a trial is conducted within a single ethnic group, the FDA requires an additional study (Mitchell, 2008). Conducting studies in several countries simultaneously helps fulfill this FDA requirement.
Because of the boom in offshore clinical trials, international health organizations have had to develop standardized regulations and guidelines. Bailey, Cruickshank, and Sharma (2006) contend that these regulations and guidelines, together with stronger intellectual property protection in developing countries, are contributing to the globalization of clinical research. However, clinical trials in developing countries are still a rather new concept. These countries have underdeveloped legal regulations for trials, a situation that attracts pharmaceutical companies that see an opportunity to avoid extra steps in bringing new medications to market. In addition, pharmaceutical companies strive to enter new markets that are very large and rapidly growing, such as those in India, China, and Russia. Thus, many companies are testing not only drugs for worldwide use but also region-specific medications.
Offshoring to Russia
Although the clinical trial market is growing in China and India, Russia is still one of the world leaders in patient enrollment (Business Insights, 2009). According to a comprehensive market report published in June 2009 by Synergy Research Group (SynRG), a Russian-based clinical research organization, even in the current global economic crisis the market for clinical trials in Russia is growing (Ward, 2009). A Russian online newspaper that provides legal information and advice—Moscow Pharmacies (Московские аптеки)—reported that between 2000 and 2005, 2,015 clinical studies were approved in Russia, 50% of which were international (i.e., sponsored by non-Russian companies). Most of the international studies tested original, new medications, while the Russian studies evaluated the bioequivalence of generic drugs.
In the past decade, the Russian Federation has become one of the primary locations for U.S. medical testing. U.S. pharmaceutical companies are drawn to Russia for clinical trials because of the country’s diverse population, still-developing legal system, and overall lack of domestically produced medications. Russia is a large market for medications, and Russian law prohibits importing medications without testing them in the country. In addition, Russia has a centralized hospital system, which makes the process of recruiting participants relatively cheap and fast. The medical system is not in good shape and average incomes are not high, so trials often are not a choice but a necessity for patients with few treatment alternatives. Moreover, participants are generally “naïve,” and their diseases are often advanced; the combination of these two factors provides a perfect baseline for scientific study. And finally, doctors who become investigators in clinical trials can make 10 times their usual salary by recruiting patients (Lustgarten, 2005).
As a world leader in patient enrollment in clinical trials, Russia can serve as a comprehensive example for exploring the characteristics of informed consent documentation in the international arena. Anecdotal evidence suggests that most of this documentation is written by technical writers in the United States and then translated into Russian. By understanding the legal and medical systems and the economic situation in Russia, technical writers can better anticipate the informational needs of the participants of clinical trials and thus complete their tasks more effectively.
The United States and Russia: The Impact of Legal and Cultural Differences on Informed Consent Documents
The benefits of offshoring clinical trials are evident, but critics wonder if, in the rush for savings, pharmaceutical companies fail to consider the ethical pitfalls (e.g., Normile, 2008). Bioethicists point out that the rights of participants in international studies are often trampled, because people in other countries respond differently to informed consent procedures and documents (Moodley, Pather, & Myer, 2005). In addition, some guidelines in the international standardization regulations leave much open to interpretation, which allows the companies to take advantage of the participants. For example, the ICH-GCP requirement for sponsors to make sure that clinical trials are “adequately monitored” can only be effective if it is effectively implemented (Glickman et al., 2009). Some U.S. laws governing clinical trials contradict international laws; this affects clinical studies in Russia, as Russia is still developing its own code for medical research and, in the meantime, abides by international standards. Moreover, both the U.S. and international legal systems can be in conflict with the contexts of people’s lives and their culturally determined mindsets. The following examples illustrate how legal differences and cultural contradictions affect informed consent documentation to the detriment of participants of clinical trials.
International Legal Debate: The Use of Placebo
International regulation and standardization attempts have often run into trouble because new directives are in conflict with the laws of a specific country. For example, regulations of the U.S.-based FDA contradict some of the international guidelines of the World Medical Association (WMA). The Declaration of Helsinki—the best-known policy statement of WMA regarding clinical trials—was amended in 2000–2002 on three major issues: limitation of placebo use, stronger requirement for trial sponsors to provide medical care to participants after the study is finished, and public registration of clinical trials before recruiting the first subject (Normile & Marshall, 2008). In October 2008, the FDA—which previously referenced the Helsinki Declaration as the basis for clinical trial regulation—amended its requirements. To avoid inconsistency, the FDA now accepts results of clinical trials from overseas if they do not comply with the Helsinki Declaration but rather with the ICH-GCP (Fiscus, 2009).
As a result, critics say that the FDA requirements are now less demanding in the protection of human rights of participants. According to Stuart Rennie, a bioethicist at the University of North Carolina, this decision by the FDA does not stand up to scrutiny since it “would seem to encourage pharmaceutical companies to cut ethical corners when working abroad. … The GCP is more open to the use of placebos and does not mention conflicts of interest, the need to publish results, or post-trial access to care” (Normile & Marshall, 2008, p. 516).
Many U.S. informed consent documents are created and sent to foreign countries without addressing this conflict. In my translation work with informed consent documents, I often encountered sentences such as these two [emphasis added]: “There is an agreement between health care experts and regulatory authorities that in order to obtain reliable and valid results of medication efficacy placebo-controlled studies are necessary” and “Regulatory authorities such as the FDA (Food and Drug Administration) and the EMEA (European Medicine Evaluation Agency) can only grant approval for medications if their efficacy has been proven to be unambiguous, which means superior to placebo.”
Such statements can be hard to decipher for an English-speaking patient because of their jargon, and they could become utterly confusing in an international setting, as well as provide grounds for litigation. The two sentences assume that all health care experts and all regulatory authorities agree on using a placebo; they imply that the only way to prove unambiguous efficacy of a drug is to compare it with placebos. However, many experts and regulatory agencies (e.g., WMA) consider the use of a placebo necessary only if no known medication exists for a particular disease. Comparing the experimental medication with an existing drug can provide conclusive results. Thus, treating participants with placebos in a blind study (a study in which participants do not know whether they are taking a placebo, an experimental drug, or a patented drug) when they could be treated with a patented medication can be unjustified and extremely detrimental to their health. The conflict about the use of placebos is just one of many examples of legal tensions in multicountry trials.
Patients’ Access to Clinical Trial Regulations
While the FDA relies on GCP standards for questions about clinical trials, in Russia the situation is not so transparent. A new law—Надлежащая клиническая практика (Appropriate Clinical Practice)—was passed in 2005, but it merely recommends rather than prescribes procedures for clinical trials. Another law—О лекарственных средствах (About Pharmaceutical Products)—was passed in 1998 to regulate everything from clinical trials to wholesale of medications; since then, it has been amended five times. An industry standard—ОСТ 42-511-99: Правила проведения качественных клинических исследований в Российской Федерации (Rules for Conducting Quality Clinical Studies in the Russian Federation)—was passed in 1998.
The list of laws, decrees, and standards does not stop here. A model law—О защите прав и достоинства человека в биомедицинских исследованиях в государствах— участниках СНГ (Protection of Human Rights and Dignity in Biomedical Studies in Countries—Members of the Commonwealth of Independent States, 2005)—regulates a state’s guarantee to protect the rights, dignity, autonomy, and integrity of an individual in biomedical testing. The opening paragraph of this law states that the statute is based on the provisions of the state constitution, as well as the principles of the Nuremberg Code, the WMA’s International Code of Medical Ethics, the Helsinki Declaration, the Convention on Human Rights and Biomedicine of the Council of Europe, the International Ethical Guidelines for Biomedical Research Involving Human Subjects of the Council for International Organizations of Medical Sciences (CIOMS), the GCP provisions of the World Health Organization (WHO), and WHO recommendations concerning the ethics of clinical trials. It is a praiseworthy attempt to combine all these international standards for clinical trials, but it fails to address the contradictions among the regulations. These contradictions make it extremely hard for participants to find information about clinical trials, especially in a country such as Russia, where Internet access is still a luxury in many smaller towns.
Problems with Terminology
Since standardization of clinical trial laws is still problematic, it is no surprise that differences exist between the United States and Russia in terminology, oversight, and understanding of the procedures. For example, in the United States you can only register a “pharmaceutical product,” while in Russia you can register a substance. In clinical trials in Russia, for example, the acetaminophen in TYLENOL® Arthritis Pain or the paracetamol in TYLENOL® Extended Relief could be the study drug, while in the United States it would have to be the specific form of acetaminophen used in children’s TYLENOL® Suspension Liquid or the TYLENOL® Arthritis Pain 150 mg caplet. Furthermore, differences exist in exclusion criteria between the two countries: In Russia, underage orphans, pregnant women,1 military personnel, and prisoners may not take part in clinical studies. In the United States, the participation of these groups is strictly regulated but permitted. Even the terms “clinical trial” and “informed consent” may cause difficulties. The concepts behind the two terms are new to Russian patients, who often have only a vague idea about them or completely misunderstand what they entail.
Agency and Privacy of the Patients
The legal regulations of any country are paramount; by complying with them, technical writers can attempt to ensure the ethical treatment of the participants of clinical studies. However, experiences in my career as a translator and interpreter, along with recent publications in the United States and Russia, indicate that following laws sometimes creates an ethical question in itself, because the traditions and mindsets of the people involved in trials often contradict the legal provisions. If law becomes the sole foundation for information in informed consent, patients are often unable to concentrate on the information, to make an informed decision, and can sometimes even refuse to participate.
In Russia, families of patients take an active role in health care: They go with the patients to doctors’ visits and research information on the condition. When a serious illness or terminal condition is discovered, doctors often consult first with the family to discuss the best way to inform the patient. The doctor and family may decide not to inform the patient at all. The usual rationale in such a decision is that if there is no hope for treatment and recovery, at least the person can die in peace. My family held on to this rationale when they decided not to inform my grandmother about the terminal nature of her illness.
However, the law in the United States and Russia dictates that fully conscious patients who do not suffer from a mental illness need to make their own informed decision about participating in clinical trials and must independently sign an informed consent form. Informed consent documents often start with study protocol titles (e.g., A Randomized, Placebo-Controlled, Phase 1/2 Study of X in Subjects With Metastatic Colorectal Cancer) and introductory sentences such as “You are being invited to participate in a research study because you have a colorectal tumor.” For a patient, the news of an illness can come from an informed consent brochure, even if the family is there to soften it.
Law and Life Context
In countries like Russia, where a large part of the population is at the poverty level, people may overlook the dangers of a clinical trial if there is no other option for treatment (Fiscus, 2009). Russia’s best doctors are migrating to the clinical trial industry because it is so lucrative; at the same time, many people cannot afford drugs in what is considered a “free” medical system. For many patients, taking part in trials is the only way to have access to treatment and medications. Lustgarten describes the case of a former metal worker and late-stage cancer patient, Ershov, for whom participation in a clinical trial offered the only chance to “get $800 worth of drugs a month at no cost, reliable access to doctors, and at least the hope of a cure” (Lustgarten, 2005, p. 66). The average monthly wage in Russia in 2008 was $694.3 (World Bank, 2009); the average monthly retirement income in 2004 was $66.4 (Ohtsu & Tabata, 2005).
If patients are aware of their condition but cannot afford treatment and are advised to take part in a clinical trial, how much time are they likely to spend reading the typical informed consent booklet: 15–20 single-spaced pages replete with medical terms? This problem is common in the United States as well, since a large percentage of the population does not have sufficient health insurance or has no health insurance at all.
Even though in the United States patients may trust their doctors, they are encouraged to ask questions. In Russia, patients usually place great trust in their medical providers; if the study doctor has a positive attitude about a clinical trial, the patient is likely to skim through the informed consent or hardly read it at all. In the Ershov case, the study doctor confided that 90% of his patients sign the form right away. Ershov himself said, “They told me the treatment was safe. I trust my doctor completely” (Lustgarten, 2005, p. 67).
According to a recent study published in Moscow Pharmacies, because of their blind trust in doctors and because they do not bother to read the informed consent documents, patients taking part in clinical studies do not know how to store the medication (99%), are not aware of the need to discontinue participation in any other study (86%), do not realize that the study may be discontinued before the date discussed (63%), and do not know that they should tell their family doctor they are participating in a study (53%).
Benefits for an Individual Versus Benefits for Society
Looking at Ershov’s interview as described by Lustgarten, we need to focus on two words: “treatment” and “cure.” Therapeutic misconception is not confined to the United States; it is even more common in clinical trials in Russia. Since these trials are still a rather new concept in Russia, many participants do not have a clear understanding of them. For some, they are the only hope for a cure. For others, they seem like experiments on human guinea pigs. The latter opinion results from lack or misinterpretation of information and from media coverage of clinical trial “busts” (e.g., testing vaccines on infants in Volgograd—a trial in which parents did not have clear information).
Informed consent documents do not offer sufficient help in this situation. The following two sentences illustrate how vaguely the potential social and personal benefits are sometimes described in informed consent documents [emphasis added]: “It is hoped that the information learned from this study will increase the knowledge and understanding of colorectal tumor” and “X seems to activate changes in tumor cells that cause them to either stop growing or die, with few effects on normal cells.”
King et al. (2005) explores the language used in informed consent documents to describe benefits of clinical trials to participants and come to the following conclusion:
Because benefits to society—described in federal research regulations as contributions to generalizable knowledge—can only be realized in the future, they should be readily distinguishable from benefits to subjects. However, when consent forms describe the ultimate aim of the line of research or the mechanism of action of the experimental intervention without differentiating these from potential benefits for subjects in the current trial, it may be difficult to distinguish between benefits to subjects and benefits to society (p. 2).
All these factors have important implications for how technical writers create informed consent documentation, since they influence the way technical writers design the documentation and what information they choose to include. These factors also present additional challenges for achieving one of the primary goals in technical communication: making information clear and unambiguous for readers.
Implications for Technical Writers
Differences in clinical trial laws, access to regulations, terminology, treatment of agency/privacy of patients, life context, culturally determined doctor-patient relationships, and attitudes toward clinical trials and their benefits in the United States and Russia affect informed consent documentation to the detriment of participants of clinical trials. However, technical writers have long emphasized the need to be “user advocates” and the importance of “user-centered design” (see, for example, Blakeslee, 2010; Faber & Johnson-Eilola, 2002; Johnson, 1998; Johnson-Eilola, 1996).
In health care communication, technical writers are taking a central role, in which their “responsibilities for the persuasiveness of documents and compliance with evolving regulations have increased dramatically” (Tomlin, 2008, p. 289). In the context of international clinical trials—in which the demands of law and the needs of patients often overlap but more frequently conflict—technical writers should challenge themselves to develop and adopt strategies that could help them cope with the ongoing challenges and make their efforts more effective. The following seven courses of action are based on the contradictions discussed in the previous section.
- Researching the laws. To best serve the interests of participants, technical writers need to stay up-to-date on clinical trial legislation in the United States and on international research regulations. A list of Web sites that could be a start for investigating laws in the United States and Russia, as well as international codes, is provided at the end of this article (see Sites for Researching Laws and Regulations). Potential clinical trial participants are not likely to know the laws, so technical writers should inform them and provide as much balanced information as possible. The example of placebo use, described in the previous section, is just one of the areas that need to be handled with care so as not to confuse patients or be the cause of litigation.
For example, when designing informed consent documents for clinical trials in Russia, technical writers need to address the following questions: Should the differences in the legal requirements be mentioned? How should exclusion criteria be addressed? Does any additional information on the study design (e.g., the reasons for using a placebo) need to be provided? How should the tested medication be described in relation to its ingredients, dosages, and methods of administration?
- Providing access to law. The ambiguities in the developing Russian law on clinical trials make it extremely hard for participants to find information about trials, which means that technical writers need to help orient them in this legal “ocean.” In addition, Internet access is still a luxury in many small towns, which makes tracking the changes in the regulations virtually impossible.
To address the problem of access to information, technical writers need to explore the possibilities of including additional legal information in consent documents. This is a rather challenging task—it requires knowledge of the law and a re-thinking of the organization of informed consent documents. Meanwhile, readability studies (e.g., Berg et al., 2001) suggest that the reading level for informed consent documents should be in the range between 5th and 10th grade; adding information will make the documents longer, which negatively affects retention.
- Researching terminology. Technical writers who specialize in health care and, in particular, in clinical trial documentation must be familiar with the terminology, and the international context often makes even greater demands on their knowledge. The concepts and terminology with which technical writers are familiar (e.g., “inclusion criteria”) may have different meanings in other countries, so writers need to provide a point of reference for readers.
In addition, the level of understanding of clinical trial terminology varies around the world. Since trials are a new concept in Russia, many patients do not have a clear idea of what informed consent is. The term used in Russia—информированное согласие—is a direct translation from English and has the same legalistic sound to it. Technical writers need to start by explaining what the process actually is, including the fact that it exists to protect patients rather than investigational staff and facility. Writers should make clear that, for example, patients have the right to decline without losing any health care benefits, the right to have any questions answered before consenting, and the right to withdraw their consent at any point during the study.
However, technical writers work under tight deadlines, and it is not realistic to ask every writer who specializes in health care to become an expert on the laws of multiple countries as well as their varying terminologies. Thus, it is important for technical writers who know that their documents will be translated to develop good working relationships not only with study teams but also with localization specialists. These professionals specialize on the country into whose language they are translating and can give expert advice on the law or provide direction in researching it.
- Respecting the notions of privacy and agency in different cultures. Technical writers who are writing for international clinical trials need to be aware of the differences in the culture and mindsets of their target audience—potential trial participants—and the possibility that their customs and traditions are at odds with those of the United States. Such awareness has serious implications: To participate in clinical studies, patients must sign informed consent forms, and they need to familiarize themselves with all appropriate information about the trial to make such a decision. Families may participate in the health care of their relatives, but they cannot sign trial documents if the patient has clinical and legal capacity.
Even though drugs are usually tested on patients who have an underlying condition, some patients might not have much information about their illness. If they do not know the full extent of their condition and they first learn the details from an informed consent form, they will require help understanding the implications. A consent form that starts with “You have been invited to participate in this study because you have …” and then goes on to describe the study design could be unnecessarily shocking and could create more questions than answers. Since it is hard to interact with actual participants in international clinical trials and receive user feedback, technical writers have to conduct research and communicate with localization specialists to obtain materials for audience analysis: to determine how much and what kind of information they need to provide in the consent document.
- Encouraging questions and discussion. For many Russian patients, participation in clinical trials offers the only hope of receiving appropriate medical treatment. In this context, using boilerplate templates determined by FDA regulations or provided by WHO (the primary task of these templates seems to be not to inform participants but to legally protect the investigator and the sponsor) essentially eliminates the possibility for discussion and thus real comprehension.
The current design of informed consent documents needs to be altered to include mechanisms for comprehension self-checks, which could signal to a patient areas where he or she needs to ask questions. Such self-checks could include comprehension questionnaires, in which patients are asked to remember the most important parts of the consent information. Staff could review the questionnaires to see if patients require more help to understand the implications of the trial. Also, consent forms should provide space to record patients’ questions and any additional information received from the doctors to more accurately reflect the extent of information exchange.
- Addressing differences in doctor-patient relationships. As we have already seen in the previous section, Russian patients tend to place more blind trust in their doctors than American patients do. While all participants need to sign consent forms, many Russian patients tend to disregard the informational pages. Technical writers should emphasize in a summary the importance of reading the whole document. Several authors (e.g., Berg et al., 2001) suggest discussing not just the risks of the trial but also the inconveniences of participation, which can have direct effect on patients’ lives.
In other words, technical writers need to make documents more user-centered to help “users facing technically difficult and sometimes frightening information” (Kim et al., 2008, p. 336). Again, it is important that technical writers work in close contact with their localization colleagues, who could become cultural interpreters and supply new insights about international audiences. Such insights will provide technical writers with necessary information for analyzing the needs of participants in international clinical trials.
- Explaining the concept of benefits. Some American patients lack understanding about benefits in medical trials, because they (1) cannot differentiate between individual benefits and benefits to society; (2) do not comprehend that the likelihood of benefits might be low; and (3) do not understand that participating in medical trials is not the same as receiving treatment. In an international context, these three issues related to therapeutic misconception are exacerbated, owing to more problematic access to health care and the nature of the doctor-patient relationship in some countries. In addition, when informed consent documents are translated and localized, ambiguities may be added and obscure parts of the text may be mistranslated. To prevent this from happening, technical writers need to keep the following strategies in mind (adapted from King et al., 2005):
- Avoid inconsistent or confusing terminology by keeping terms simple, defining them succinctly throughout the text, limiting variations of the terms that refer to the experimental intervention, and describing potential direct benefits consistently.
- Avoid misleading implications about receiving treatment by letting the patient know that the primary goal of the trial is to help future patients, making a clear distinction between this goal and direct health benefits to the patient, being honest if no direct benefit to the participant is possible, and using terminology that has a “research” rather than a “treatment” connotation.
- Avoid vagueness about potential benefits by eliminating “empty” benefit statements (e.g. “you may not benefit if you join this study”); discussing each type of benefit separately; providing precise descriptions of reasonably possible direct benefits, including their nature, magnitude, duration, likelihood, and limits; and explaining the links between potential direct benefits and receiving the study medication.
To cope with these challenges, technical writing instructors should offer training that provides an understanding of the drug development process, the interconnections between the writing and research processes, and research strategies (Bonk, 1998). Such training should include “instruction in persuasion, collaboration, strategic and project management, … and the location and interpretation of FDA regulations” (Tomlin, 2008, p. 289); it should teach how to relate skills and knowledge to specific tasks.
This article looked at how the work of technical writers is complicated by differences in U.S. and Russian law, as well as the role of customs, traditions, and mindsets of participants in international clinical trials. When technical writers design informed consent documents for international clinical trials, they need to remember not only the requirements of legal authorities and regulatory agencies but also the concerns and needs of the primary audience of such texts: the participants. The article suggested strategies to address the problematic issues that arise from the interrelation of law and culture and that technical writers can adopt and adapt for their practices.
These strategies could be further developed to discuss ways to present information in consent documents for other countries. The following areas of research could provide additional insights:
- The study of more sites (e.g., India, China, South America) of international clinical trials to better understand what differences might influence informed consent documentation. While the example of Russia has implications for other countries involved in clinical trials, it cannot be used as a generalization for all the existing problems.
- The role of technology in facilitating patient understanding and retention of information about clinical trials. Some authors have looked into the possibilities of video and audio recordings or multimedia interfaces as part of the informed consent process (e.g., Henry et al., 2009; Kim et al., 2008). For example, Kim et al. (2008) explore a “user-centered design process to develop online support for informed consent in pediatric Phase 1 research trials” (p. 335).
- The mechanisms for individualized patient education materials in clinical trials. Bental, Cawsey, and Jones (1999) and Di Marco et al. (2008) point out that it is very hard to address all the right issues in generic paper brochures, because patients have different concerns, different levels of literacy and knowledge, and so on. These authors suggest individualizing informational documents for clinical trial participants.
Technologies for facilitating the informed consent process and creating individualized consent documents may not be available in countries with few resources, but exploring these two possibilities is a step forward and can provide valuable insights for informed consent documents in the United States—a country where multiple languages and cultures are at work every day.
The strategies described in this article can help technical writers enhance the consent process for clinical trials; address the needs of participants, including their fears and hesitations; and educate health care professionals about what effective documents can achieve and the difference they can make. Sometimes this task will require the strength to withstand the stereotypes of designs and forms, but it will also give technical writers an opportunity to make a difference.
I am very grateful to Dave Clark, Rachel Spilka, and Stefan Ruediger for their support and comments on earlier drafts; to three anonymous referees and to the guest editors, Kirk St.Amant and Martine Courant Rife, for their helpful feedback that was an invaluable contribution to this article.
1. Unless specific medications for pregnant women are tested and necessary information can only be obtained in such trials; there should be no risk to the pregnant woman and fetus.
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About the Author
Tatiana Batova is a PhD student in professional writing at the University of Wisconsin-Milwaukee. Before starting the PhD program at UWM, she worked as a localization specialist, project manager, and translation editor. She has served as director of the Midwest Association of Translators and Interpreters. She has an MA in foreign languages and literature from UWM and an MA in pedagogy and foreign languages from Tula State University in Russia. Her major research interests are in the areas of international business and technical writing, cross-cultural communication, and content management. Phone: (414) 736-8074. E-mail: firstname.lastname@example.org; email@example.com.
Manuscript received 1 October 2009; revised 19 February 2010, accepted 19 March 2010.