If you haven’t already heard there are changes coming to everyone’s favourite…the ICH GCP.
For a consolidated look at just the changes you can take a look at them all in one document I’ve created.
Here is the link to download: https://andrewmilroy.files.wordpress.com/2015/11/consolidated-changes-to-ich-e6r2-by-andrew-milroy-14-nov-2015.pdf
Towards Trans-cultural Process Based Ethics: Silencing critics of clinical trials in developing countries
As things now stand, Ethical Pluralism and the avoidance of a modern ethical imperialism of sorts, allows for exploitation or at a minimum the appearance of exploitation to persist, and has been taken off the table concerning acceptable strategies in dealing with developing countries, making its acceptability something of a moot point. If taken stringently, in practice it would undue years of work towards universalising ethical codes for research involving human subjects. Moral universalism has intrinsic and inescapable problems tied to imperialism of values and cultural norms. It offers a totalitarian stance on how things ought to be and all but ignores important differences between cultures. Procedural pluralism an approach not discussed in depth herein is on the right track but is only just beginning to come to some structured definition. Although it is arguably currently allowing for exploitation to persist with large variances in the capacity of local institutions to properly assess clinical trials and a remaining difficulty with what to take as “standard of care”, these can be overcome with capacity building clauses and reviews from developing world taken as universal decisions.
The position being proposed is for a new push towards a trans-cultural process based ethics. Trans-cultural process based ethics hopes to take the procedural necessity from ethical pluralism but aims to shape it into a more stringent universal form with standards. Questions then diverge from whether ethical committees merely exist, to whether they meet universalized standards of what is required to function unbiased and in a manner which could silence the criticism. With a new look at the role capacity plays in claims of exploitation, criticism of pharmaceutical companies which say that the absence or malfunction in many instances of local ethics committees is what is making developing countries so attractive to large pharmaceutical companies may be silenced.
ARE CLINICAL TRIALS EXPLOITATIVE?
Large pharmaceutical companies are increasingly moving into international markets to develop therapies, making clinical trials in the developing world a core component of their business models. Looking at the United States, one third of their trials are being conducted outside the country, many in countries which are still developing. Pushing this move is the desire to help local health care concerns, lower costs, and expedite the time taken to conduct these trials. Reasons for these trials are there contribution to the development of national economies and health care systems, along with enabling higher standards of quality. They offer global access to academic expertise and patient populations.
In countries which have healthcare budgets of less than ten dollars per person per year, clinical research can benefit entire communities. Backed with large funding budgets a country can benefit greatly by maintaining an environment ideal for clinical research through which entire healthcare systems can be developed and capacity built. For pharmaceutical companies developing nations offer pools of patients not otherwise found in the developed world, allowing for research on drugs to take place which would otherwise be impossible.
With the increase of clinical trials in the developing world there has been increased concern after several well known instances, one of which involving HIV trials in Africa, have fed the fires of criticism over these trials. The criticism largely revolves around the double standard of care which can be found in developing countries that allow for these trials to exist and increase in popularity because of savings associated with cost and time.
Declarations such as that of the Declaration of Helsinki, adopted virtually universally in the world, show a trend which aims at making ethical considerations more explicit when determining ethical acceptability of humans in research. However, with these declarations providing minimum recommendations to what is acceptable there are radical differences between how they are interpreted in practice. High standards which are espoused in these declarations critics say, are not being espoused in practice and questions such as “Is it ethically acceptable to confine subjects in the control arm to treatments which are considered substandard in the sponsoring country of the study?” persist in delivering heated debate in the medical community.
Serious questions about which standard of care to use in a control arm of a study remain and are compounded with questions of the ability of ethics committees in developing countries to function properly. On one side we can find proponents of a position which would push for ethical pluralism, allowing for local ethics committees and standards to trump positions and therapies found in developed countries. The other side can be summarized within a moral universalism ideology. They push for universal standards and weighting of principles, uphold opinions coming from ethical committees and review boards from developed nations, and demand standard of care requirements to be defined as that of best globally rather than locally. Depending on which of the two camps one finds themselves in changes the entire appearance of the debate.
As with all debates that have been around for some time, there is a third camp which takes a sort of middle ground. They can be said to fall within procedural pluralism which can be taken to mean that the declarations which are been agreed upon are universal in some sense, although they are goals rather than principles and which in their attainment, can be ethically allowed to differ from differing cultural contexts. They place tremendous importance to local ethics committees and their autonomy to make decisions for the communities for which they serve. It is perhaps within this arm of the debate that progress can be made at turning what appear to be exploitative practices into clear examples of ethical research.
This proposal looks at the current disparity between international and local standards, what it means to the existing debate, implicitly shows a need for a new approach for approval of international clinical trials, and states what that approach could be.
EXPLOITATION (Universalism vs. Pluralism)
Due to less stringent regulatory constraints and income disparities, trials can be carried out quicker and cheaper in a developing country rather than developed. A core criticism to international clinical trials is that the level of income found in developing countries means that people are often more willing to participate. They are, it is argued, more vulnerable than participants in wealthier nations.
Problems for ethical research in a developing country include 1) a health system which may function inadequately, leaving patients to join trials mistakenly in search of treatment, 2) troubles offering well informed participants able to make informed consent due to poverty, illiteracy, a hierarchical doctor-patient relationship, and lack of access to treatment, and 3) a lack of training needed to conduct trials according to ethical standards. These problems pose serious questions to the ethical nature of any trial being conducted in such a setting.
There is such a discrepancy between clinical environments that many have even ventured to ask if fair participant selection, a core tenant of ethical research, is even possible. This is attributed to the fact that participants could very well be coerced through economic reasons or because they cannot receive treatment otherwise. In instances found in India where physicians are paid large sums to recruit participants, it is difficult to ensure that procedures meant to provide consent are genuine and legitimate. Again those who argue for an ethical pluralism stance for administrating clinical trials, sway opponents by noting that clinical research in these communities is necessary and that it meets their standards, that is the local standards, for what is ethically permissible. Similarly, with informed consent difficulties surrounding its acquisition are usually excused with claims that the guidance of universal declarations do not take into account local circumstances where Western consent procedures may conflict with cultural norms and notions of autonomy.
Despite the shortcomings of local capacity to adhere to international standards, ethical pluralist side with a position that would have local ethics committees and their outputs trump that of developed nations on the position that their autonomy and standards should be recognized. Moral Universalists however, claim that it is precisely the low standards at the local level which allow for exploitation to occur. If universal standards were used, such exploitation would not exist. The disagreement on whether to use universal standards or a pluralistic stance on what is to be acceptable is precisely what has led to criticisms of exploitation.
STANDARD OF CARE Developed vs. Developing
The question of whether exploitation exists in clinical trials which are conducted in developing countries is unresolved. This is largely dependent on how existing universal principles found in declarations such as the Declaration of Helsinki are interpreted at the local level. For example, withholding in a control arm a therapy known to be effective albeit in an intensive and expensive form for the common local therapy is construed as ethical relativism. Moral Universalists would argue that you cannot withhold the better Western treatment or therapy. What should be taken as the “standard of care” whether local or global is of crucial importance and is far from being resolved.
Standard of care, or the best standard of care is meant to protect vulnerable participants from being unjustly harmed through deprivation of standard medical treatment while in an experiment. In essence no patient in a trial funded by the United States should be denied the ‘standard of care’ available in the United States. Problems arise though when one examines the reaction to changes made to the Declaration of Helsinki which stated it is a worldwide best standard which should be used in a control arm. The reaction was a rejection by every national and international committee that reviewed it. This rejection however, leaves the benchmark for control arms arguably far too low. Moral Universalists would claim that we cannot waiver on a global standard of care which ought to be provided while ethical pluralists would claim a more context based answer involving the local treatments which are commonly provided can be sufficient. The claim that all research subjects are entitled to minimum guarantees that are transnational and non-negotiable is widely accepted although realisation of these entitlements often falls far short in practice. There is another double standard at play though which complicates the debate and that is of the quality and capacity of ethics committees in developing countries to participate at international standards.
There have been incidences of ethics committees in wealthy countries approving studies that would not be allowed in their own country to be conducted in poor countries. Critics, Moral Universalists, claim that different standards of research ethics are being applied, one for developed countries, the other for the developing ones. Cultural differences are being used to validate clinical trials with the primary responsibility for assessing proposals left with the relevant ethical review committees in the developing countries. This is problematic because it is often more difficult to conduct scientifically sound research in countries where basic healthcare is not widely available and research ethics committees are underdeveloped or absent.
A major concern is the ability of regulatory agencies and ethics committees to function properly, without their functioning, declarations and the principles found within cannot be upheld as intended. With wide disparities in terms of economic, social standing, and their health care systems, the fear is that the lack of capacity in developing countries jeopardizes the rights of research patients by bringing in trials which should not be approved. One study for example showed that only 56% of the 670 researchers surveyed in developing countries stated that their research had been reviewed by a local institution review board or health ministry. In another study 90% of published clinical trials conducted in China in 2004 did not report ethical review of protocol.
Those who would continue clinical trials in countries where a lack of proper oversight is abundantly clear, highlight the need for a different balance to be met between risks and benefits where there are differences between resources and health conditions. This leads again to their falling under an ethical pluralist stance which shows that from their side, a study may be acceptable in one country but not in another because of differences in wealth or burdens of disease. The very fact of a discrepancy of acceptability does not warrant a claim of exploitation it is said. Those who continue to defend such trials associate a great deal with the process requirements of a trial. From the fact that the trials are being supported by local governments and approved by ethics committee, it should be seen as a trial which is not exploiting the local population but rather one which builds the local healthcare system and capacity of participating healthcare practitioners.
International conventions have little practical guidance for when local ethics committees show a lack of capacity. More worrisome is that although guidelines advise investigators to submit proposals for ethical review in both the funding and receiving country, they are silent on the question of primacy concerning differing opinions on acceptability and other matters. If we look to the Council for International Organizations of Medical Sciences than the problem can be said to be exacerbated when it states “the host country’s ethics committee has a ‘special responsibility’ on matters of detail of a trail, such as acceptability of plans to obtain informed consent, while committees in the sponsoring body need only to be satisfied that the trial conforms broadly to the ethical standards prevailing in their own country.” This gives an almost trumping status to ethical review committees which may have major shortcomings concerning expertise. Only a handful of African nations currently have the capacity for growing international requirements. They along with non-African nations tend to have under-developed mechanisms and procedures. The countries which have the most vulnerable populations to clinical trials have the least developed systems to review such research.
As questions such as whether the ‘best proven diagnostic and therapeutic method’ refers to international standards or should we take local resources into consideration, and whether healthcare needs and budgets justify ethical standards in developed countries to differ from the developing, the debate on whether these trials are exploitative will continue. Although there is already a recognized need for universal guidelines and regulatory requirements to minimize conflicting reports, these guidelines can often led to two very different answers. Agreements must be made further on the weighting of principles and exactly how the more detailed aspects of clinical trials in the local context can universally be handled. An additional ‘layer’ of guidance between the universal and contextual is clearly needed. Similarly harmonisation is needed between existing research ethics guidelines.
While there has been considerable work done on what makes clinical research ethical, with the development of principles and benchmarks to guide ethics committees, there has been considerably less research done on overcoming differences in views of exploitative research or claims made thereof. As claims of exploitation can severely damage the reputation of a pharmaceutical company which is conducting clinical trials in developing countries in what is considered by them ethical and non-exploitative there must be a method developed to deal with resolving claims of exploitation. We should go further than consensus building on what is deemed ethical. We should aim to develop a method whereby existing principles are untangled from one another and whereby through, an as of yet developed structure for analysis, clinical trials which involve multiple cultures may realize their benefits without facing what some times appear as inherent criticisms of exploitation.
David M. Studdert and Troyen A. Brennan “Clinical trials in developing countries: scientific and ethical issues”. The Medical Journal of Australia 1998 Vol 169 pg.545-548
Ezekiel J. Emanuel et al. “What Makes Clinical Research in Developing Countries Ethical? The Benchmarks of Ethical Research”. JID March 1, 2004 Vol 189 pg. 930-937
Francis P. Crawley “Developing Clinical Trials in Africa: Building the Scientific, Regulatory and Ethical Frameworks”. Journal for Clinical Studies Nov. 2008 pg.16-17
Greg Koski et al. “Research Involving Human Subjects in Developing Countries”. The New England Journal of Medicine July 12 2001 Vol 345;2 pg. 136-138
Michael J. Selgelid “Module Four: Standards of Care and Clinical Trials”. Developing World Bioethics 2005 Vol. 5;1 pg. 55-72
National Bioethics Advisory Commission “Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries”. Report and Recommendations of the National Bioethics Advisory Commission April 2001 pg. 1-12
P.K. Julka “Clinical Trials in India: Dilemmas for Developing Countries”. Issues in Clinical Research April 2007 pg. 69-71
Yousefi- Nooraie et al. “Registration of Clinical Trials: How Developing Countries Could Prepare for the Upcoming Storm”. Archives of Iranian Medicine July 2008 Vol 11;4 pg. 361-363
Seth W. Glickman et al. “Ethical and Scientific Implications of Globalization of Clinical Research”. The New England Journal of Medicine Feb. 19 2009 Vol 306;8 pg. 816-823
Soren Holm “Moral pluralism”. The ethical aspects of biomedical research in developing countries, Proceedings of the Round Table Debate Oct. 1 2002 pg. 9-10
Wemos Foundation “Call for Ethical Clinical Trials in Developing Countries”. Fair Drugs Feb. 2009 pg. 1-7
Wemos Foundation “Do European registration authorities ascertain whether clinical trials in developing countires have been conducted in an ethical manner?” Fair Drugs June 2007 pg. 1-8
by Andrew Milroy – HRPP and CQA Manager (Merita CQA)
Online training is becoming increasingly popular in nearly every field allowing for training of professionals from the comfort of their own office or home. In the field of clinical research there are several well known online training tools such as the TCPS 2 CORE Tutorial offered by the Interagency Advisory Panel on Research Ethics, and the Collaborative Institutional Training Initiative’s (CITI) ICH GCP training.
Listed below are six online training tools, including those mentioned above, that offer clinical research coordinators a means by which they can upgrade their credentials, refresh their knowledge, or just remain current with the latest developments and ideas.
The TCPS 2 Tutorial – Course on Research Ethics (CORE)
CORE provides an applied approach to the guidance provided in TCPS 2. This self-paced course is a media-rich learning experience that features interactive exercises and multi-disciplinary examples. CORE consists of eight modules ranging from Core Principles to REB Review. It is designed primarily for the use of researchers and REB members – though anyone may take this course and print their own certificate of completion.
Collaborative Institutional Training Initiative’s (CITI) Program’s Good Clinical Practice (GCP)
GCP courses are suitable for research teams involved in clinical trials of drugs, biologics, and devices.
GCP for Clinical Trials with Investigational Drugs and Medical Devices (U.S. FDA focus) is suitable for individuals proposing to conduct clinical trials of drugs and devices primarily in the U.S. and/or who would prefer a more U.S. FDA-centric curriculum.
GCP for Clinical Trials with Investigational Drugs and Biologics (ICH Focus) is suitable for individuals involved in clinical trials on drugs and biologics when the research may be international or where the individuals would prefer a more ICH-focused curriculum. This ICH E6 GCP Investigator Site Training meets the Minimum Criteria for ICH GCP Investigator Site Personnel Training identified by TransCelerate BioPharma as necessary to enable mutual recognition of GCP training among trial sponsors.
GCP for Clinical Trials with Investigational Medical Devices is most appropriate for organizations or individuals who desire a more international-focused GCP curriculum or a more device-focused program.
Ethical and Regulatory Aspects of Clinical Research
This course is offered by the NIH to anyone interested or involved in the ethics of clinical research with human subjects. Participants represent multiple disciplines including research teams, IRB members, physicians, psychologists, nurses, social workers, administrative staff, students, and others.
Introduction to the Principles and Practice of Clinical Research (IPPCR)
The Introduction to the Principles and Practice of Clinical Research (IPPCR) is offered by NIH and is a course to train participants on how to effectively conduct clinical research. The course focuses on the spectrum of clinical research and the research process by highlighting epidemiologic methods, study design, protocol preparation, patient monitoring, quality assurance, and Food and Drug Administration (FDA) issues. Other areas covered include data management and ethical issues, including protection of human subjects, building a budget, plus many special topics.
Training and Resources in Research Ethics Evaluation (TRREE)
TRREE is headed by a consortium of interested persons from Northern and Southern countries. It aims to provide basic training, while building capacities, on the ethics of health research involving humans so that research meets highest standards of ethics and promotes the welfare of participants. TRREE achieves this goal primarily by developing a training programme with local collaborators. In its initial stages TRREE focused primarily, but not exclusively, on the needs of African countries.
TRREE provides free-of-charge access to:
e-Learning: a distance learning program and certification on research ethics evaluation
e-Resources: a participatory web-site with international, regional and national regulatory and policy resources
The e-learning programme is based on internationally recognized ethical principles and regulations. It integrates local issues and perspectives from low-and middle-income countries, most notably from African countries, that are relevant to all those who must ensure the protection of research participants and who promote highest ethical standards.
The Lab: Avoiding Research Misconduct
In “The Lab: Avoiding Research Misconduct,” you become the lead characters in an interactive movie and make decisions about integrity in research that can have long-term consequences. The simulation addresses Responsible Conduct of Research topics such as avoiding research misconduct, mentorship responsibilities, handling of data, responsible authorship, and questionable research practices.
This list is not exhaustive and if you are aware of other available online training tools please feel free to contact me so that I can review and consider utilizing them for training purposes.
I can be reached at email@example.com if you have any questions or would like to share additional online training tools.
TCPS 2 Tutorial :: The Interagency Advisory Panel on Research Ethics (PRE). (n.d.). Retrieved December 3, 2014, from http://www.pre.ethics.gc.ca/eng/education/tutorial-didacticiel/
Collaborative Institutional Training Initiatives. (n.d.). Retrieved December 3, 2014, from https://www.citiprogram.org/
Courses, Lectures, & Training. (n.d.). Retrieved December 3, 2014, from http://www.bioethics.nih.gov/courses/index.shtml#ethical
NIH Clinical Center: IPPCR. (n.d.). Retrieved December 3, 2014, from http://clinicalcenter.nih.gov/training/training/ippcr.html
TRAINING AND RESOURCES IN RESEARCH ETHICS EVALUATION. (n.d.). Retrieved December 3, 2014, from http://elearning.trree.org/
The Lab. (n.d.). Retrieved December 3, 2014, from http://ori.hhs.gov/thelab
Was reading “Uncle John’s Funniest Ever Bathroom Reader” and came across a piece worth sharing. Here it is:
Actual abbreviations and terms used in the ER by doctors and nurses who – by necessity – have a morbid sense of humor
TMB: Too Many Birthdays (suffering from old age)
FORD: Found On Road Dead
House Red: Blood
TRO: Time Ran Out
Frequent Flyer: Someone who is regularly taken to hospital in an ambulance, even though they aren’t sick (because it’s something to do)
Code Zero: Another name for a “Frequent Flyer.” The real radio codes range from Code 1 (not serious) to Code 4 (emergency)
Code Yellow: A patient who has wet the bed
Code Brown: (You can guess this one yourself)
FOOSH: Fell Onto Outstreched Hand (a broken wrist)
T&T Sign: Tatoos-and-teeth. (Strange but true: Patients with a lot of tatoos and missing teeth are more likely to survive major injuries.)
DFO: Done Fell Out (of bed)
MGM Syndrome: A “patient” who is faking illness and putting on a really good show
WNL: Will Not Listen
SYB: Save Your Breath, as in, “SYB, he WNL”
Insurance Pain: An inordinate amount of neck pain following a minor auto collision with a wealthy driver
ALP: Acute Lead Poisoning – a gunshot wound
ALP (A/C): Acute Lead Poisoning (Air Conditioning) – multiple gunshot wounds
Flower Sign: Lots of flowers at a patient’s bedside (may indicate the patient is a good candidate for early discharge, since they have people who can care for them)
ART: Assuming Room Temperature (deceased)
Bagged and Tagged: A corpse ready for the morgue (it’s in a body bag and has a toe tag)
AMF Yo Yo: Adios, Motherf@#*!, You’re On Your Own
Often research studies have accompanying questionnaires for qualitative aspects of the study and some of those questionnaires ask fairly sensitive information. It is important that there be concern for the participants welfare and so often REBs will ask questioned deemed too sensitive to be removed. But how do we determine a sensitive question from a normal or non-sensitive question. I believe the literature on sensitive research can help provide answers.
After reading through some of the literature I believe found a workable solution (or at least something to start a discussion) in response to the dilemma of determining when a question is too sensitive for inclusion in a questionnaire.
In the book Doing Research on Sensitive Topics by Raymond Lee (Lee 1993) he puts forward a definition of sensitive research that was widely received and accepted by more recent authors on the subject such as Virginia Dickson-Swift et al. in the book Undertaking Sensitive Research in the Health and Social Sciences: Managing Boundaries, Emotions and Risks (Dickson-Swift et al. 2008).
Lee defines sensitive research as “research which potentially poses a substantial threat to those who are or have been involved in it.” Adding to this definition, a threat can be grouped into three broad areas. The first is “intrusive threat” which deals with areas that are private, stressful or sacred e.g. sexual or religious practices. Second type is a “threat of sanction”, i.e. the research question involves the possibility of revealing information that is stigmatizing or incriminating. The third type of threat is “political threat” which refers to when researchers ask questions which “trespass” into areas that involve a social conflict involving the vested interests of the powerful in society.
Areas in which research questions are likely to be threatening include:
- where question intrudes into the private sphere or delves into some deeply personal experience;
- where the question is concerned with deviance or social control;
- where the question impinge on the vested interests of powerful persons or the exercise of coercion or domination; or
- where the question deals with things that are sacred to those being asked that they do not wish to profane.
A final comment I would like to make is that the above criteria for determining if a particular question in a questionnaire is too sensitive, cannot be used when the research topic itself is of a sensitive nature.
Please feel free to comment if you have one or ask questions.
All the best,
Researched and Written by: Andrew Milroy1
Edited by: Gordon B. Robinson , B.A.Sc. (Eng), Ph.D2.
Today in the minds of the public and certainly with potential Clinical Trial Participants, there exists a great deal of suspicion and a lack of positive attitudes towards such Trials. While awareness campaigns may improve public perception, there still are many areas for considerable improvement throughout the Trial’s life-cycle.
Purpose of the Paper
To examine Clinical Trial Researchers‘ attitudes towards Participants and specifically, towards the current, common-UHN practice of communicating Trial Results solely through Publication.
Any Trial Participant is an investment on the part of the entire research community. Once recruited, many aspects of attitudes towards and how Participants are treated go a long way towards maximum retention. Throughout and at the finish-point of a Study, where the Participant feels they were a valued member of the research team, will go considerably further towards creating a positive attitude towards Trials in the minds of the public.
Participants want the opportunity to be informed of their Trial’s results which was explained in a recent paper3. This publication reviewed the current environment regarding the communication of Clinical Trial results with Participants. It cited, as a best-practice, the Center for Information and Study on Clinical Research Participation (“CISCRP”) Program for sharing such results in lay language , similar to that in Informed Consent Forms ( “ÏCF”) . It concludes with a statement that any organization should develop industry- leading policies relating to repeated communication with Trial Participants. Not only is there an ethical foundation for the practice of communicating Clinical Trial results to Participants, it also has wide-spread support among “Stakeholders” of the Clinical Research enterprise.
Recently4, it was shown that the Chairs of Canadian REB-s overwhelmingly supported sharing results with Participants. Not only the Chairs favour sharing, studies show that a high-percentage of Participants want to be advised of a Trials results5 A study in late 2013 surveyed more than 5,600 Study Participants and discovered that learning of the results was one of the foremost reasons for participating5. Another study4 showed the percentage of those wanting to receive the results at 90 % Further, Principal Investigators themselves have been shown to be highly supportive of this sharing.
Despite wide-spread support from other “Stakeholders”, the majority of Participants never receive results4 In another Study, about 90% reported that they never learned the results from Investigators, Staff, the Institution or the Sponsors3 . Some of the numbers:
- Only 5 out of 150 Institutions surveyed had any formal mechanism for returning Research Results to Participants
- Only 6 out of 180 Leukemia Clinical Trials indicated that Participants could receive Study Results
- Only 9 out of 22 Canadian REB-s surveyed had policies addressing communication of results or required Investigators to address the issue themselves..
Eighteen Studies provide sufficient data on the overwhelming desire by Participants to receive, in layman’s language, their Study Results4. Thus, there is clear evidence that improvements in how Clinical Trials should be run, but unfortunately, Participant preferences are seldom considered when developing policy and what seems like a simple process as it is not in the cultural framework of Trial operations6. One Cancer Study reported that 86% of the Participants were not even offered the chance to receive the results at all7 while another3 showed less than 5% received results.
Often the practice of sharing Clinical Trial results, if at all, is done through publications and posting information to clinicaltrial.gov or similar on-line platforms. Further, when shared the results remain in technical language which is not in keeping with the guiding principles for Informed Consents. Such on-line platforms are meant for a different audience than Participants. It defies logic and common sense that Trial results are not offered in lay-language !! In fact, Kenneth Getz, the co-founder of CISCRP stated that such practices fail to satisfy the critical obligation to communicate results with Participants3.
Clearly Participants want to receive their Clinical Trial results and more research on this issue in not needed. Attention must be given to efficiently share results in lay-language with Participants. Doing so would provide Participants with a much-needed sense of appreciation and help considerably to build increasing trust in the Clinical Trial enterprise.
An opportunity currently exists to build stronger ties with Participants through intelligent results-sharing, before it is mandated. In March of 2014,, The European Parliament voted overwhelmingly in favour of regulations that all Clinical Trial results be accompanied with a lay-language summary. Such programs are increasingly being implemented on a voluntary basis by Sponsors to honour and thank Participants5 .
Within 5 years, pharmaceutical and biotech companies will routinely provide Clinical Trial results to study volunteers in response to regulatory mandate, public pressure and desire to strengthen relationships with those volunteers.
Although it is reasonable to believe that lay-summaries will be required, some postulate that there are barriers, which could include4 , although some of these possibilities have been negated. In fact Miller4 found that negative consequences were not a deterrent to a vast majority of Participants in one Study.
Any barriers can be overcome and there are examples of successful programs that shared results with Participants. One example is the MA.17 Trial5 which tested whether extended adjuvant therapy with the aromatase inhibitor ‘letrozole’ after ‘tamoxifen’ reduced the risk of breast cancer reoccurrence. When, mid-way through the Trial, that ‘letrozole’ improved disease-free survival, the Trial was halted and the Coordinator sent-out an e-mail to akk Study Sites 3 days before any public announcement and each Participant was immediately offered open-label to ‘letropzole’ with such greatly improved communications improving the attitudes of Participants.
Another example of exemplary communications with Trial Participants Is through the work of
‘CISCRP’ which began in 2010 when they started a program of communicating in lay-language, Trial results to Participants and have stated that they can … “easily, feasibly and affordably establish as a standard practice within organizations and industry-wide” 3 , CISCRP-lead studies showed that what a majority of Participants wanted was a small recognition and information of when the results would be available understandably to them. Further assessment indicates that such a practice is feasible and generally easy to perform.
Currently, CISCRP is assisting more than 12 companies in support of their post-Trial communication initiatives3 and although it was slow to begin, they have seen a doubling in each of the past 2 years of Sponsors joining, bringing to about 24 .
Such a communication imitative positively impacts volunteer recruitment, retention and long-term trust in the Clinical Research Trials by recognizing the Participant as a fellow “Stakeholder” in the process showing signs of respect for the risks assumed and the commitments’ made by the Participant3 .
Opportunities for Relationships
Substantial missed opportunities of building trust and establishing relationships with Study Participants are encountered when they do not receive appropriate communication. Only lay-summaries shared with Participants, rather than the current usual practice of publication, should be considered as a means of meeting ethical obligations.
With Participants and Investigative sites amongst others, all asking for Study Results and growing support from Sponsors to providing lay-summaries, there needs to be greater demand in the form of institutional policies mandating that results be shared with Participants in a form that they can understand. In addition, this policy when applied during a Trial, can yield positive results. Furthermore, in keeping with ethical standards, the plan for communication should be discussed both in the ICF and in Protocols.
Policies that increase the level of importance placed on communicating Trial Results and their subsequent enactment shows respect for the collaborative relationship between Investigators and Participants and would enhance trustworthiness of Research and Researchers.
The 3-R’s …. In order to maintain or increase the number of Recruited and Retained, Clinical Trial Participants, UHN must improve the level of Respect in which such Participants are viewed.
UHN should consider development of a country-leading, communication policy where Clinical Trial Participants are communicated with both in periodic appreciation and then, with understandable verbiage of lay-language summaries of the Trial Results.
Further, this policy would be concomitant with that of Consent Forms which mandates language at a 6th– 8th– grade education level.
Such an action on the part of UHN would be another example of how it is leading in Research Ethics compliance.
- Andrew Milroy, former Member of the UHN, Oncology-REB (’12-’14), now employed as the HRPP & CQA Manager at Merita CQA in Montreal
- Gordon B. Robinson, B.A.Sc. (Eng), Ph.D. is a Member of the UHN Oncology-REB (’07 – present ) and a Member of the Federal, Tri-Agency Panel on Research Ethics (PRE)
- Getz et al, “Meeting the Obligation to Communicate Clinical Trial Results to Study Volunteers”, Expert Review Clicial Pharmacology, 2012, 5(2), pp 149 – 150
- Shalowitz, D. I. & Miller, F. G., “Communicating the Results of Clinical Research to Participants”, PLoS Medicine, May 2008, Vol 5, Issue 5, pp 714 – 720
- Getz K & Hallinan, Z., “Creating a Standard Practice for Communicating in Lay Language to Study Volunteers”, Exp. Rev. Clin. Pharmacol., 2012, 5, pp 145 – 156
- Goodlow, B. J. & Furlong P., “Transparency as a Means to Increase Clinical Triasl Enrollment”, Drug Info. Journal, Vol. 44, pp 265 – 270
- Getz K. et al, “Providing Results to Volunteers”, App. Cliun. Trials, 19(10), 52 – 59
At work recently I’ve been going through cases of ethical misconduct for a presentation I will be delivering in the coming months and it has raised in my mind questions of therapeutic misconception.
Clearly ethical regulations and theory purport that research is for the benefit of knowledge and not the health of the participant. I.e. it’s not meant as a therapy. But is that true?
Many areas of medicine have no known treatments and people are regularly being signed up for clinical trials in the distant hope that it will benefit their condition.
For me, and perhaps some readers, this definitely raises the question of whether we are confusing participants and feeding into misconception. No doubt only the greatest intentions are meant but perhaps a review of the practice of signing up participants for the hope that it will treat them needs to be re-examined.
How does the concept of therapeutic misconception stand, or does it need to, when e.g. a cancer patient has gone through several rounds of chemo and there is really nothing left except experiment.
My worry, and how this relates to ethical misconduct is that in the past vulnerable groups have been used to push science ahead at the cost the wellbeing of participants.
I would argue that for patients who have no known standard of care and are left with either no care of experimental research that they be classified as a vulnerable population susceptible to undue influence to sign up for a study, and so be protected in research under the classification as a vulnerable population. Same as for example economically disadvantage who turn to research studies for money.
Just some thoughts. I haven’t fully developed the argument clearly but hey, this is my blog and I’ll do what I want. 🙂
After reading an article by the WSJ that came across my LinkedIn newsfeed (http://online.wsj.com/articles/the-role-of-deception-in-scientific-research-1409009297#livefyre-comment) I started thinking about deception in research.
Can deception ever be ethically justified in research? Isn’t that showing the end’s justify the means? I was always taught, not through formal study of ethics, that the end’s never justify the means. Is that old adage wrong when it comes to research ethics?
I don’t think so.
Perhaps the negative act of deception always trumps the gains. Deception does after all leave a bad impression on those on the receiving end. Doesn’t it erode trust in scientists as benevolent researchers and science in general?
We currently allow deception when it is low risk research and if there are no other ways to conduct the research. To that I say perhaps the research itself is low risk, but the risk of ruining trust in research after deception has occurred is actually high. Second, perhaps if the research cannot be done by any other means then it ought not be done at all.
Seems to me that by allowing deception we are going about research ethics willy-nilly. Deception is wrong outside of research, why allow it within research?
For now, I’m basically writing this post to just get started as I know right now I have no followers. I will be taking steps in the future to change that as I hope this blog can carve out its place in the online fora of ethics related sites and blogs.
My interest is largely in the areas I studied while in University, Bioethics, Social, and Political. I have an interest in Business ethics as well although have not studied it formally.
This Blog will largely feature content on subjects found in areas such as healthcare ethics, corruption, social justice, and corporate social responsibility. I am not going to limit myself at the moment but if I find a certain area that I enjoy writing about as I continue it may drift into a more specialized category of ethics.
Anyway, that’s all for now. Hope you enjoyed reading my first blog post on Ethics Nut.