- Email: [email protected]
Clinical research: The patients’ perspectives
Injury, Int. J. Care Injured (2008) 39, 631—635
www.elsevier.com/locate/injury
Clinical research: The patients’ perspectives Theodoros I. Tosounidis, George M. Kontakis * Department of Orthopaedics-Traumatology, University of Crete, Greece Accepted 18 December 2007
KEYWORDS Clinical research; Patient’s perspective; Randomised trials
Summary Patients’ perspectives in clinical research have become increasingly interesting and important. Much effort has recently been made to understand, evaluate and promote the patients’ active roles in and unique views on their involvement in clinical research, and how these may help resolve old and new problems in research planning, conduct and implementation. In this article issues regarding informed consent, differences between medical care and medical research, confidentiality, conflicts of interest and disclosure of study results are considered from the patients’ point of view. # 2008 Elsevier Ltd. All rights reserved.
Introduction Over the years, clinical research has proved to be the driving force behind innovation and implementation of new therapies in medicine. Now the current system of conducting clinical research is under increasing pressure. According to the Helsinki Declaration, medical research involving human subjects includes research on any identifiable human material or data.28 The evolution of evidence-based medicine and its fundamental cornerstone, the randomised controlled trial, has mandated the definite delineation of the specific role of every participant in a clinical research project. As a result, the terms of participation, the obligations, needs, requirements and restraints of the various contributors such as the clinical researchers, physicians, patients and industry, have all been re-evaluated and changed.
* Corresponding author at: 1 Pindarou Street, 71305 Heraklion, Crete, Greece. E-mail address: [email protected] (G.M. Kontakis).
The emerging therapies and innovative strategies developed through the process of clinical research constitute the core of medical progress, which ultimately must aim to benefit the health consumer, i.e. the patient. The interests of society and science should be taken into account, but the first priority should always be the interests of the patient. The World Health Organization’s Declaration of Alma Ata states that: ‘People have the right to and duty to participate individually and collectively in the planning and implementation of their care’.26 Today, knowledge of the individual patient’s perceptions regarding clinical research is becoming more interesting and useful than ever in accelerating new therapies, building trust, recruiting trial participants and resolving conflicts.4
Why do patients participate in clinical research? Many issues regarding clinical research and the participants’ views (i.e. conflicts of interest,
0020–1383/$ — see front matter # 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2007.12.025
632 implementation of innovative techniques in clinical trials and differences between conducting research and providing medical care) have recently emerged. In order to clarify the patients’ perspectives one should address the question: ‘Why do patients participate in clinical research?’ According to Poll, the first reason is to advance science and medicine and the second to obtain better treatment.4,11 The current system of combining patient care and clinical research is breaking down. The assessment of the risk:benefit ratio by ethics committees is gradually replacing the concept of research with or without direct benefit to the participant.17 Patients are now more concerned about type II errors, i.e. false-negative results that may prevent the use of an effective medication or treatment.4 At the same time they may tend to ignore possible type II errors and advocate the widespread use of an ineffective or even dangerous product.4 The above debates should hinge on the ethical prerequisite ‘to do no harm to the patients or the future patients’ in clinical research’.4 The statement of the American Medical Association’s (AMA) Code of Medical Ethics, that ‘investigators testing treatment efficacy must recognise the patient—physician relationship and exercise professional judgment and skill in the best interest of the patient’, establishes the significant role of the patient and his or her views in the planning and conduct of clinical research.8 Taking into account the above, it becomes clear that in order to move forward, clinical research should incorporate the validation of the patients’ perspectives into its philosophy. By the term ‘patients’ one should consider not only those who participate in specific research, but also their families and communities, and future potential patients. Emanuel et al.6 suggested that clinical care and clinical research should minimise the potential risks and enhance the expected benefits, and that the benefits for individuals as well as the knowledge gained for society should outweigh the risks, before any study is performed. From the patients’ point of view, expectation of a benefit for their health is the main reason for participating in clinical research, i.e. ‘If I thought the drug might cure me . . .’27 Patients are very concerned about honesty on all sides as to the true benefits and risks of the study. This implies thorough knowledge of the relevance of the study to participants and/or their community.27 Thus, from the patients’ point of view clinical research and medical care are strongly linked. The question whether there should be a clear benefit for the patient in a clinical research project or the uncertainty about the particular treatment is known as ‘clinical equipoise’. The concept of ‘individual direct benefit from research’ does prevail in some
T.I. Tosounidis, G.M. Kontakis European legislation. However, the distinction between research with and without direct benefit will imminently be replaced by the evaluation of the risk:benefit ratio by ethics committees.17
Informed consent The backbone of patients’ participation in a clinical study is informed consent. The Belmont Report suggests that informed consent should consist of three components: information about the research that is going to take place, evaluation of risks and benefits, and the ability of the participant to knowingly volunteer.24 An informed and trusting patient participates in clinical research willingly and is going to enhance the process. The idea of informed consent to participation in a clinical study is multifactorial and includes issues beyond an agreement to participate. The principles that rule the conduct of modern medicine, i.e. autonomy, beneficence and justice,1 should be implemented in decision-making. According to the Helsinki Declaration, patients who participate in a clinical trial should be adequately informed about the trial’s aims, methods, expected benefits and potential risks.28 However, recent changes in laws governing the ethics of medical practice mandate a more comprehensive decision-making process (shared decision-making) in which information flows from the physician or researcher to the participant and vice versa.3 Despite the fact that considerable efforts have been made to promote recruitment of competent and genuine volunteers in clinical trials, many studies7,10,19,22,23 suggest that the information provided to patients taking part in clinical trials is too technical or is incomprehensible. At the NIH Workshop Proceedings ‘Inviting Public Participation in Clinical Research’,27 participants pointed out that there is a need to improve informed consent documents in terms of their length and also their perceived purpose, which is to explain full details of the research and not to protect the researchers from litigation. Another issue addressed in this workshop was the need to use decision-making and information aids in the informed decision-making process in a clinical trial. The time spent by the researcher on explaining the study was also a concern. Other suggestions for the informed consent process included using patient advocates to assist potential study participants, setting standards to develop informed consent documents at a sixth-grade reading level, and providing a mechanism for obtaining ongoing informed consent so that participants have the option to remove themselves from a study at any time.27
Clinical research: The patients’ perspectives Ferguson7 interviewed patients participating in clinical trials for the treatment of chronic medical conditions, in order to investigate their views on the amount of the information provided and of their understanding of that information. The conclusion was that there was a difference between the patients’ perceptions and the reality of the situation. This was in spite of the fact that the patients felt that they were given an appropriate amount of information and that they were able to understand it.
Privacy, confidentiality and respect An important concern worth mentioning relates to the protection of the privacy and confidentiality of participants during the course of the research. It is a commonplace among people involved in research concerning human subjects that medical information differs in important ways from other personal data, being more intimate and sensitive. Because of this, greater protection of privacy is needed and substantial restraints on the use and disclosure of medical information, even for legitimate research purposes, are imposed by the Health Insurance Portability and Accountability Act (1996).16 Be treated as a human being, i.e. as an individual unique person and not as a case number, is of paramount concern for patients. The convictions that ‘individuals should be treated as autonomous agents’ and that ‘persons with diminished autonomy are entitled to protection’ constitute fundamental principles of the Helsinki Declaration.28 The monstrous crimes against humanity that were conducted by Nazi doctors led to the formulation of the Nuremberg Code.21 The first adoption of the World Medical Code Association Declaration of Helsinki in 1964 was followed by numerous episodes of human experimentation such as the Tuskegee Institute case and the Willowbrook State School case, which in turn led to the Belmont Report in 1979.21 Nowadays respect for human rights is considered an absolute prerequisite for the planning and conduct of any clinical research. In addition, patients as the primary consumers of the clinical research require empathy from researchers, i.e. that professionals understand and care about the individual participants and their disorders.27.
Conflicts of interest in clinical research Conflict of interest by definition exists when financial or other personal considerations have
633 the potential to compromise or bias professional judgment or objectivity,21 both by possible increase of risk for the participants and by undermining the scientific integrity of the research.12 Hampson et al.12 conducted personal interviews with patients enrolled in cancer research trials. He concluded that the vast majority of the participants had no or few worries about financial relationships that researchers or institutions might have with drug companies. Similarly Weinfurt et al.25 pointed out that, although patients wanted to know about financial interests, their desire and ability to understand the nature and the implication of those financial interests varied considerably. Grady et al.9 used face-to-face semi-structured interviews with individuals actively participating in biomedical research. The authors explored the views of participants concerning investigator financial information and the usefulness to participants of that information. The results showed that the majority wanted to have ‘all the cards on the table’ and to receive information about investigators’ financial interests. However, the actual information when received was described as low priority, not relevant, troublesome or having no impact on their research participation decisions.9 Kahn14 concluded that the solution to the crisis in clinical research regarding public trust was to protect the patients’ interests and to enhance trust, in combination with disclosure in an attempt to reduce conflicts. Furthermore, Kim et al. state that nondisclosure of financial conflicts of interest contradicts to potential research participants’ values and wishes.15
Study results and post-study options Recently substantial attention has been drawn to research participants’ views on information provided during the study about study progress, disclosure of results and post-study options that exist after the end of the research.5 Discussion regarding the notification of research results27 indicated that these should be communicated to the patients as a thank-you letter and summary. It was also pointed out that in situations where the researchers were obliged by law to keep information confidential, such as the results of genetic tests, the researchers should disclose these constraints at the beginning of the study. The difference between the disclosure of interim information compared with the final results was also a point of interest. The importance of the communication of negative information to the study participants before its release to the general public was debated as well.27
634 Madsen et al.18 in a survey of investigations of the attitudes of potential research participants concluded that the lack of feedback concerning results of trials was a significant contributor to a negative change in attitude toward participation.
Closing remarks Patients belong to the community of clinical research consumers. As J.F. Kennedy said: ‘Consumers have the right to be informed, the right to choose, and the right to be heard’ (J.F. Kennedy, 1962, The Consumer’s ‘The Consumer’s Bill of Rights’’).13 Boote et al.2 argued that consumer involvement in research enhanced quality and clinical relevance. On the other hand, there is the opinion that consumer involvement in clinical research trials may render these projects costlier and longer, and at the same time consumers may bias certain health issues.20 Nevertheless, in order to improve and enhance the state of clinical research, it is essential to build trust and relationships among all stakeholders.27 At the core of this concept lie the reasons for patients’ participation in a clinical research project, their role in research planning, the terms of their consent, issues concerning privacy and confidentiality, knowledge and disclosure of the conflicts of interest, study results and post-study options, all to be reviewed from the patients’ perspectives. Furthermore, specific issues such as participants’ views about sham surgery and placebo medication, research in vulnerable populations such as children and the critically ill, and research in genetics and orphaned fields of medicine, are due to be further explored and delineated. Today more than ever it has become clear that the increasing development and ethical complexity of clinical research demand the adoption of a system which takes into consideration the perspectives of every participant in clinical research. The numerous aspects of patients’ beliefs, behaviours and attitudes about their involvement are currently being included in order to move from the authoritative perspective of clinicians and researchers into a more synergistic approach to the concept of clinical research.2 Undoubtedly considerable steps forward have been taken, but many more are yet to be taken if patients’ perspectives in clinical research are to be fully explored and effectively used in clinical research.
Conflict of interest There are no conflicts of interest associated with this review article.
T.I. Tosounidis, G.M. Kontakis
References 1. Beuchamp TL, Childress JF. Principles of biomedical ethics. New York: Oxford University Press; 1994. 2. Boote J, Telford R, Cooper C. Consumer involvement in health research: a review and research agenda. Health Policy 2002;61:213—36. 3. Bryant D, Bednarski E, Gafni A. Incorporating patient preferences into orthopaedic practice: should the orthopaedic encounter change? Injury 2006;37:328—34. Epub February 14 2006. 4. Cohen PD, Herman L, Jedlinski S, et al. Ethical issues in clinical neuroscience research: a patient’s perspective. Neurotherapeutics 2007;4:537—44. 5. Criner GJ. Framing the forum: medical ethics in large-scale, interventional respiratory clinical trials. Proc Am Thorac Soc 2007;4:171—5. 6. Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA 2000;283:2701—11. 7. Ferguson PR. Patients’ perceptions of information provided in clinical trials. J Med Ethics 2002;28:45—8. 8. Glass KC, Waring D. The physician/investigator’s obligation to patients participating in research: the case of placebo controlled trials. J Law Med Ethics 2005;33:575—85. 9. Grady C, Horstmann E, Sussman JS, Hull SC. The limits of disclosure: what research subjects want to know about investigator financial interests. J Law Med Ethics 2006;34:592—9. 10. Grossman SA, Piantadosi S, Covahey C. Are informed consent forms that describe clinical oncology research protocols readable by most patients and their families? J Clin Oncol 1994;12:2211—5. 11. Gullo K. New survey shows public perception of opportunity to participate in clinical trials has decreased slightly from last year. Harris Interactive Healthcare News 2005; 5:1—14. Available at: http://www.harrisinteractive.com/news/newsletters/healthnews/HI_HealthCareNews2005Vol5_lss06.pdf. Accessed 3 October 2007. 12. Hampson LA, Agrawal M, Joffe S, et al. Patients’ views on financial conflicts of interest in cancer research trials. N Engl J Med 2006;355:2330—7. 13. Herxheimer A. The rights of the patient in clinical research. Lancet 1988;2:1128—30. 14. Kahn JP. Beyond disclosure: the necessity of trust in biomedical research. Cleve Clin J Med 2007;74:49—59. 15. Kim SY, Millard RW, Nisbet P, Cox C, Caine ED. Potential research participants’ views regarding researcher and institutional financial conflicts of interest. J Med Ethics 2004;30:73—9. 16. Kulynych J, Korn D. The effect of the new federal medical privacy rule on research. N Engl J Med 2002;346:201—4. 17. Lemaire F. Patient care versus research: does clinical research provide individual benefit to patients enrolled in trials? Curr Opin Crit Care 2004;10:565—9. 18. Madsen S, Holm S, Riis P. Ethical aspects of clinical trials: the attitudes of the public and out-patients. J Intern Med 1999;245:571—9. 19. Meade CD, Howser DM. Consent forms: how to determine and improve their readability. Oncol Nurs Forum 1992;19:1523—8. 20. Nilsen ES, Myrhaug HT, Johansen M, Oliver S, Oxman AD. Methods of consumer involvement in developing healthcare policy and research, clinical practice guidelines and patient information material. Cochrane Database Syst Rev 2006;3: CD004563. 21. Parvizi J, Tarity TD, Conner K, Smith JB. Institutional review board approval: why it matters. J Bone Joint Surg Am 2007;89:418—26.
Clinical research: The patients’ perspectives 22. Priestley K, Campbell C, Valentine C, et al. Are patient consent forms for research protocols easy to read? BMJ 1992;305:1263—4. 23. Tarnowski K, Allen D, Mayhall C, et al. Readability of pediatric biomedical research informed consent forms. Pediatrics 1990;85:58—62. 24. The Belmont Report. Ethical principles and guidelines for the protection of human subjects of research. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. 18 Apr 1979. http://www.nih training.com/ohsrsite/guidelines/belmont.html. Accessed 3 October 2007. 25. Weinfurt KP, Friedman JY, Allsbrook JS, et al. Views of potential research participants on financial conflicts of interest: barriers and opportunities for
635 effective disclosure. J Gen Intern Med 2006;21: 901—6. 26. WHO 1978. World Health Organization. Declaration of Alma Ata: Report of the International Conference on Primary Health Care. Geneva: WHO; 1978. 27. Inviting public participation in clinical research: building trust through partnerships. Workshop sponsored by the National Institutes of Health Director’s Council of Public Representatives (COPR), in partnership with the NIH Public Trust Initiative, October 26-27, 2004. Available at:http:// copr.nih.gov/reports/October_2004_COPR_WORKSHOP_Pro ceedings.pdf Accessed 3 October 2007. 28. World Medical Association. Declaration of Helsinki. Ethical principles for medical research involving human subjects. 2004. Available at: www.wma.net/e/policy/b3.htm.
www.elsevier.com/locate/injury
Clinical research: The patients’ perspectives Theodoros I. Tosounidis, George M. Kontakis * Department of Orthopaedics-Traumatology, University of Crete, Greece Accepted 18 December 2007
KEYWORDS Clinical research; Patient’s perspective; Randomised trials
Summary Patients’ perspectives in clinical research have become increasingly interesting and important. Much effort has recently been made to understand, evaluate and promote the patients’ active roles in and unique views on their involvement in clinical research, and how these may help resolve old and new problems in research planning, conduct and implementation. In this article issues regarding informed consent, differences between medical care and medical research, confidentiality, conflicts of interest and disclosure of study results are considered from the patients’ point of view. # 2008 Elsevier Ltd. All rights reserved.
Introduction Over the years, clinical research has proved to be the driving force behind innovation and implementation of new therapies in medicine. Now the current system of conducting clinical research is under increasing pressure. According to the Helsinki Declaration, medical research involving human subjects includes research on any identifiable human material or data.28 The evolution of evidence-based medicine and its fundamental cornerstone, the randomised controlled trial, has mandated the definite delineation of the specific role of every participant in a clinical research project. As a result, the terms of participation, the obligations, needs, requirements and restraints of the various contributors such as the clinical researchers, physicians, patients and industry, have all been re-evaluated and changed.
* Corresponding author at: 1 Pindarou Street, 71305 Heraklion, Crete, Greece. E-mail address: [email protected] (G.M. Kontakis).
The emerging therapies and innovative strategies developed through the process of clinical research constitute the core of medical progress, which ultimately must aim to benefit the health consumer, i.e. the patient. The interests of society and science should be taken into account, but the first priority should always be the interests of the patient. The World Health Organization’s Declaration of Alma Ata states that: ‘People have the right to and duty to participate individually and collectively in the planning and implementation of their care’.26 Today, knowledge of the individual patient’s perceptions regarding clinical research is becoming more interesting and useful than ever in accelerating new therapies, building trust, recruiting trial participants and resolving conflicts.4
Why do patients participate in clinical research? Many issues regarding clinical research and the participants’ views (i.e. conflicts of interest,
0020–1383/$ — see front matter # 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2007.12.025
632 implementation of innovative techniques in clinical trials and differences between conducting research and providing medical care) have recently emerged. In order to clarify the patients’ perspectives one should address the question: ‘Why do patients participate in clinical research?’ According to Poll, the first reason is to advance science and medicine and the second to obtain better treatment.4,11 The current system of combining patient care and clinical research is breaking down. The assessment of the risk:benefit ratio by ethics committees is gradually replacing the concept of research with or without direct benefit to the participant.17 Patients are now more concerned about type II errors, i.e. false-negative results that may prevent the use of an effective medication or treatment.4 At the same time they may tend to ignore possible type II errors and advocate the widespread use of an ineffective or even dangerous product.4 The above debates should hinge on the ethical prerequisite ‘to do no harm to the patients or the future patients’ in clinical research’.4 The statement of the American Medical Association’s (AMA) Code of Medical Ethics, that ‘investigators testing treatment efficacy must recognise the patient—physician relationship and exercise professional judgment and skill in the best interest of the patient’, establishes the significant role of the patient and his or her views in the planning and conduct of clinical research.8 Taking into account the above, it becomes clear that in order to move forward, clinical research should incorporate the validation of the patients’ perspectives into its philosophy. By the term ‘patients’ one should consider not only those who participate in specific research, but also their families and communities, and future potential patients. Emanuel et al.6 suggested that clinical care and clinical research should minimise the potential risks and enhance the expected benefits, and that the benefits for individuals as well as the knowledge gained for society should outweigh the risks, before any study is performed. From the patients’ point of view, expectation of a benefit for their health is the main reason for participating in clinical research, i.e. ‘If I thought the drug might cure me . . .’27 Patients are very concerned about honesty on all sides as to the true benefits and risks of the study. This implies thorough knowledge of the relevance of the study to participants and/or their community.27 Thus, from the patients’ point of view clinical research and medical care are strongly linked. The question whether there should be a clear benefit for the patient in a clinical research project or the uncertainty about the particular treatment is known as ‘clinical equipoise’. The concept of ‘individual direct benefit from research’ does prevail in some
T.I. Tosounidis, G.M. Kontakis European legislation. However, the distinction between research with and without direct benefit will imminently be replaced by the evaluation of the risk:benefit ratio by ethics committees.17
Informed consent The backbone of patients’ participation in a clinical study is informed consent. The Belmont Report suggests that informed consent should consist of three components: information about the research that is going to take place, evaluation of risks and benefits, and the ability of the participant to knowingly volunteer.24 An informed and trusting patient participates in clinical research willingly and is going to enhance the process. The idea of informed consent to participation in a clinical study is multifactorial and includes issues beyond an agreement to participate. The principles that rule the conduct of modern medicine, i.e. autonomy, beneficence and justice,1 should be implemented in decision-making. According to the Helsinki Declaration, patients who participate in a clinical trial should be adequately informed about the trial’s aims, methods, expected benefits and potential risks.28 However, recent changes in laws governing the ethics of medical practice mandate a more comprehensive decision-making process (shared decision-making) in which information flows from the physician or researcher to the participant and vice versa.3 Despite the fact that considerable efforts have been made to promote recruitment of competent and genuine volunteers in clinical trials, many studies7,10,19,22,23 suggest that the information provided to patients taking part in clinical trials is too technical or is incomprehensible. At the NIH Workshop Proceedings ‘Inviting Public Participation in Clinical Research’,27 participants pointed out that there is a need to improve informed consent documents in terms of their length and also their perceived purpose, which is to explain full details of the research and not to protect the researchers from litigation. Another issue addressed in this workshop was the need to use decision-making and information aids in the informed decision-making process in a clinical trial. The time spent by the researcher on explaining the study was also a concern. Other suggestions for the informed consent process included using patient advocates to assist potential study participants, setting standards to develop informed consent documents at a sixth-grade reading level, and providing a mechanism for obtaining ongoing informed consent so that participants have the option to remove themselves from a study at any time.27
Clinical research: The patients’ perspectives Ferguson7 interviewed patients participating in clinical trials for the treatment of chronic medical conditions, in order to investigate their views on the amount of the information provided and of their understanding of that information. The conclusion was that there was a difference between the patients’ perceptions and the reality of the situation. This was in spite of the fact that the patients felt that they were given an appropriate amount of information and that they were able to understand it.
Privacy, confidentiality and respect An important concern worth mentioning relates to the protection of the privacy and confidentiality of participants during the course of the research. It is a commonplace among people involved in research concerning human subjects that medical information differs in important ways from other personal data, being more intimate and sensitive. Because of this, greater protection of privacy is needed and substantial restraints on the use and disclosure of medical information, even for legitimate research purposes, are imposed by the Health Insurance Portability and Accountability Act (1996).16 Be treated as a human being, i.e. as an individual unique person and not as a case number, is of paramount concern for patients. The convictions that ‘individuals should be treated as autonomous agents’ and that ‘persons with diminished autonomy are entitled to protection’ constitute fundamental principles of the Helsinki Declaration.28 The monstrous crimes against humanity that were conducted by Nazi doctors led to the formulation of the Nuremberg Code.21 The first adoption of the World Medical Code Association Declaration of Helsinki in 1964 was followed by numerous episodes of human experimentation such as the Tuskegee Institute case and the Willowbrook State School case, which in turn led to the Belmont Report in 1979.21 Nowadays respect for human rights is considered an absolute prerequisite for the planning and conduct of any clinical research. In addition, patients as the primary consumers of the clinical research require empathy from researchers, i.e. that professionals understand and care about the individual participants and their disorders.27.
Conflicts of interest in clinical research Conflict of interest by definition exists when financial or other personal considerations have
633 the potential to compromise or bias professional judgment or objectivity,21 both by possible increase of risk for the participants and by undermining the scientific integrity of the research.12 Hampson et al.12 conducted personal interviews with patients enrolled in cancer research trials. He concluded that the vast majority of the participants had no or few worries about financial relationships that researchers or institutions might have with drug companies. Similarly Weinfurt et al.25 pointed out that, although patients wanted to know about financial interests, their desire and ability to understand the nature and the implication of those financial interests varied considerably. Grady et al.9 used face-to-face semi-structured interviews with individuals actively participating in biomedical research. The authors explored the views of participants concerning investigator financial information and the usefulness to participants of that information. The results showed that the majority wanted to have ‘all the cards on the table’ and to receive information about investigators’ financial interests. However, the actual information when received was described as low priority, not relevant, troublesome or having no impact on their research participation decisions.9 Kahn14 concluded that the solution to the crisis in clinical research regarding public trust was to protect the patients’ interests and to enhance trust, in combination with disclosure in an attempt to reduce conflicts. Furthermore, Kim et al. state that nondisclosure of financial conflicts of interest contradicts to potential research participants’ values and wishes.15
Study results and post-study options Recently substantial attention has been drawn to research participants’ views on information provided during the study about study progress, disclosure of results and post-study options that exist after the end of the research.5 Discussion regarding the notification of research results27 indicated that these should be communicated to the patients as a thank-you letter and summary. It was also pointed out that in situations where the researchers were obliged by law to keep information confidential, such as the results of genetic tests, the researchers should disclose these constraints at the beginning of the study. The difference between the disclosure of interim information compared with the final results was also a point of interest. The importance of the communication of negative information to the study participants before its release to the general public was debated as well.27
634 Madsen et al.18 in a survey of investigations of the attitudes of potential research participants concluded that the lack of feedback concerning results of trials was a significant contributor to a negative change in attitude toward participation.
Closing remarks Patients belong to the community of clinical research consumers. As J.F. Kennedy said: ‘Consumers have the right to be informed, the right to choose, and the right to be heard’ (J.F. Kennedy, 1962, The Consumer’s ‘The Consumer’s Bill of Rights’’).13 Boote et al.2 argued that consumer involvement in research enhanced quality and clinical relevance. On the other hand, there is the opinion that consumer involvement in clinical research trials may render these projects costlier and longer, and at the same time consumers may bias certain health issues.20 Nevertheless, in order to improve and enhance the state of clinical research, it is essential to build trust and relationships among all stakeholders.27 At the core of this concept lie the reasons for patients’ participation in a clinical research project, their role in research planning, the terms of their consent, issues concerning privacy and confidentiality, knowledge and disclosure of the conflicts of interest, study results and post-study options, all to be reviewed from the patients’ perspectives. Furthermore, specific issues such as participants’ views about sham surgery and placebo medication, research in vulnerable populations such as children and the critically ill, and research in genetics and orphaned fields of medicine, are due to be further explored and delineated. Today more than ever it has become clear that the increasing development and ethical complexity of clinical research demand the adoption of a system which takes into consideration the perspectives of every participant in clinical research. The numerous aspects of patients’ beliefs, behaviours and attitudes about their involvement are currently being included in order to move from the authoritative perspective of clinicians and researchers into a more synergistic approach to the concept of clinical research.2 Undoubtedly considerable steps forward have been taken, but many more are yet to be taken if patients’ perspectives in clinical research are to be fully explored and effectively used in clinical research.
Conflict of interest There are no conflicts of interest associated with this review article.
T.I. Tosounidis, G.M. Kontakis
References 1. Beuchamp TL, Childress JF. Principles of biomedical ethics. New York: Oxford University Press; 1994. 2. Boote J, Telford R, Cooper C. Consumer involvement in health research: a review and research agenda. Health Policy 2002;61:213—36. 3. Bryant D, Bednarski E, Gafni A. Incorporating patient preferences into orthopaedic practice: should the orthopaedic encounter change? Injury 2006;37:328—34. Epub February 14 2006. 4. Cohen PD, Herman L, Jedlinski S, et al. Ethical issues in clinical neuroscience research: a patient’s perspective. Neurotherapeutics 2007;4:537—44. 5. Criner GJ. Framing the forum: medical ethics in large-scale, interventional respiratory clinical trials. Proc Am Thorac Soc 2007;4:171—5. 6. Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA 2000;283:2701—11. 7. Ferguson PR. Patients’ perceptions of information provided in clinical trials. J Med Ethics 2002;28:45—8. 8. Glass KC, Waring D. The physician/investigator’s obligation to patients participating in research: the case of placebo controlled trials. J Law Med Ethics 2005;33:575—85. 9. Grady C, Horstmann E, Sussman JS, Hull SC. The limits of disclosure: what research subjects want to know about investigator financial interests. J Law Med Ethics 2006;34:592—9. 10. Grossman SA, Piantadosi S, Covahey C. Are informed consent forms that describe clinical oncology research protocols readable by most patients and their families? J Clin Oncol 1994;12:2211—5. 11. Gullo K. New survey shows public perception of opportunity to participate in clinical trials has decreased slightly from last year. Harris Interactive Healthcare News 2005; 5:1—14. Available at: http://www.harrisinteractive.com/news/newsletters/healthnews/HI_HealthCareNews2005Vol5_lss06.pdf. Accessed 3 October 2007. 12. Hampson LA, Agrawal M, Joffe S, et al. Patients’ views on financial conflicts of interest in cancer research trials. N Engl J Med 2006;355:2330—7. 13. Herxheimer A. The rights of the patient in clinical research. Lancet 1988;2:1128—30. 14. Kahn JP. Beyond disclosure: the necessity of trust in biomedical research. Cleve Clin J Med 2007;74:49—59. 15. Kim SY, Millard RW, Nisbet P, Cox C, Caine ED. Potential research participants’ views regarding researcher and institutional financial conflicts of interest. J Med Ethics 2004;30:73—9. 16. Kulynych J, Korn D. The effect of the new federal medical privacy rule on research. N Engl J Med 2002;346:201—4. 17. Lemaire F. Patient care versus research: does clinical research provide individual benefit to patients enrolled in trials? Curr Opin Crit Care 2004;10:565—9. 18. Madsen S, Holm S, Riis P. Ethical aspects of clinical trials: the attitudes of the public and out-patients. J Intern Med 1999;245:571—9. 19. Meade CD, Howser DM. Consent forms: how to determine and improve their readability. Oncol Nurs Forum 1992;19:1523—8. 20. Nilsen ES, Myrhaug HT, Johansen M, Oliver S, Oxman AD. Methods of consumer involvement in developing healthcare policy and research, clinical practice guidelines and patient information material. Cochrane Database Syst Rev 2006;3: CD004563. 21. Parvizi J, Tarity TD, Conner K, Smith JB. Institutional review board approval: why it matters. J Bone Joint Surg Am 2007;89:418—26.
Clinical research: The patients’ perspectives 22. Priestley K, Campbell C, Valentine C, et al. Are patient consent forms for research protocols easy to read? BMJ 1992;305:1263—4. 23. Tarnowski K, Allen D, Mayhall C, et al. Readability of pediatric biomedical research informed consent forms. Pediatrics 1990;85:58—62. 24. The Belmont Report. Ethical principles and guidelines for the protection of human subjects of research. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. 18 Apr 1979. http://www.nih training.com/ohsrsite/guidelines/belmont.html. Accessed 3 October 2007. 25. Weinfurt KP, Friedman JY, Allsbrook JS, et al. Views of potential research participants on financial conflicts of interest: barriers and opportunities for
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