Informed Consent & Research Risk

Posted on behalf of Liz Horn, Director of Genetic Alliance‘s BioBank. Read more about Liz on our ‘Experts’ page!

The informed consent process and the Institutional Review Board (IRB) are traditional systems for managing research risk. IRBs, established by the National Research Act in 1974, are charged with approving, monitoring and reviewing research, with the primary goal of protecting the rights of human subjects. IRBs are mandated by the Federal Government as part of the Code of Federal Regulations (CFR) (Part 46 [Protection of Human Subjects] of Title 45 [Public Welfare] and FDA regulations on IRBs at 21 CFR 56). (This document compares the FDA and HHS Human Subject Protection Regulations.)

Broadly, each research study must consider the following:

• Respect for persons – How can our research processes enact respect?
• Beneficence – How can we assure our research is achieving benefits? And clear benefits for whom?
• Justice – How can we proceed equitable and fairly while addressing current injustices in the system?

Specifically, according to the ICH GCP guidelines, IRBs should review the following: the research protocol(s) and any amendment(s), all written informed consent document(s) and any document revisions, recruitment procedures for participants including advertisements, all written information provided to participants, the investigator’s brochure, any available safety information, information about payments and compensation available to participants, the investigator’s current curriculum vitae and/or other documentation evidencing qualifications, and any other documents that the IRB may need to fulfill its responsibilities. IRBs also review the research protocol and other related documents at regular intervals (usually at least once a year). The principal investigator is responsible for reporting to the IRB any protocol deviations or changes to the protocol, all adverse reactions, and any new information that may adversely affect the safety of the participants.

Several recent events have influenced the public narrative on research ethics, including Rebecca Skloot’s book “The Immortal Life of Henrietta Lacks”, the destruction of 5 million discarded newborn blood spots in Texas, and the Havasupai/ Arizona State University settlement. Given these events, it is possible that business as usual practices can cause harm, and we often cannot anticipate what harm looks like.

This suggests that traditional systems for managing risk, including IRB review and the informed consent process, may not be sufficient, and additional standards and stewardship practices may be needed to guide us. As good stewards, we must engage our community and the public, be transparent about research practices and intentions, communicate openly and clearly, and ask permissions before using samples outside of original scope or intentions.

• Do you think our traditional systems for managing risk are sufficient?
• How do we manage the process of informed consent with low levels of health and science literacy?
• What rights do individuals have to their data or samples?
• Should we ask individuals permission to use their samples in other ways? If yes, what infrastructure is needed?

Informed Consent: A Misnomer in the World of Ever Increasing Genetic Research Capabilities?

On behalf of Alice Hawkins, Ph.D. Candidate. Read more about Alice in our ‘Experts’ section!

The requirement of participant consent to be involved in research stems from past research atrocities such as the Tuskegee Syphilis Study or Nazi War Experiments, in which participants were not fully informed (or informed at all) about the research in which they were participating. Autonomy, recognized as one of the four key bioethical principles in both clinical and research ethics requires that we ‘respect the person’, be it a research participant or patient. This entails ensuring individuals who are entering a research trial, or agreeing to  a certain treatment strategy of surgery, are fully informed as to the risks, benefits and limitations  of the specific research or treatment they are considering undergoing. Ensuring individuals are fully informed, and are able to make a free, uncoerced decision, allows them to adequately evaluate participation in relation to their unique circumstance and thus make the most appropriate choice as to whether or not they consent. This well-warranted respect and adherence to the principle of informed consent is of particular relevance in the North American Medical and Research context, in which individual choice is given primacy.

However whether it is feasible, reasonable and justified to require fully informed  consent is called into question by some more recent developments in the research arena such as genetic biobanks. Briefly, biobank research involves large collections of human tissue that may have been collected retrospectively (through pathology departments) or prospectively (through research studies). Biobanks, especially when combined with other biobanks, offer a wealth of information for researchers that may be used for genetic analyses to examine questions such as prevalence of certain genetic polymorphisms in a population, relevance of demographic changes, pharmacologic considerations and genetic markers for diagnostic tests. Yet because the potential research use of these biobanks is unknown at the time they are collected, it is not possible to obtain full informed consent for those who donate (either knowingly through research, or unknowingly through pathology departments) samples which can potentially  be used for beneficial research.

The question then occurs as to what to do about this? How should we balance the need to respect a person’s autonomy with the potential for valuable research? Do we still have to obtain consent? Is ‘blanket’ or ‘broad’ consent (i.e. agreeing to research which falls within a broad spectrum) adequate? What is the most ethical approach?

The key to innovation

On Tuesday there was an interesting discussion on the innovative edge of the Canadian economy on CBC [Innovation: Losing the Edge]. It highlighted reasons for the decline of innovation and possible solutions for its long-term development. Problematic aspects addressed, included: the narrow view of policy on high-tech sectors, the sometimes ‘too local’ approach, the missing focus on the commercialization process of innovative ideas and the underinvestment into human capital – including forms of education, the support of raw talent and the pace of hiring and firing.
All of the contributors, Roger Martin (Rotman School of Management), Ilse Treurnicht (MaRS Discovery District), Armine Yalnizyan (Canadian Centre for Policy Alternatives) and Kunal Gupta from Polar Mobile, agreed upon the fact that there need to be long-term solutions for Canada to get its edge in innovation back. They suggested education elements fostering innovative thinking, the overall prioritization of innovation in politics, tax breaks for growing companies and an immigration strategy that fosters entrepreneurs and raw talent.
These are all viable solutions to being innovative in the long-run, but what the discussion was missing from my perspective was the networking aspect of creating such as success. Only once, Ilse Treurnicht raised the issue of connecting young to growing companies in order for them to learn and become bigger. To my mind, this aspect should go beyond this connection. As said in the clip, government is spending a lot of money on innovation, but the output is never properly measured or tracked. Instead, government often overspends on high-tech development without addressing the underlying structure for innovation to happen and affect the overall economy. Local networks are the ones that enable knowledge flows between firms and the cooperation between government, research and industry – regardless of the sector. Networking leads to higher levels of productivity, innovation and employment. The rational for the relationship between networking and performance levels is that 1) productivity is enhanced by lowering transaction costs, which is fuelled by local industry agglomeration; 2) innovation is dependent on interactive knowledge exchange, enhanced by networking; and 3) employment results from new business formation is aided by learning, communication and commercialization – attributes that have been ascribed to networks (1, 2). Further, in order to create communication channels between actors and create a vision for stakeholders, a broker, network manager or facilitator can help to not only connect different actors in the network, but also help government to fund at the right time, with the right amount, the right entrepreneurs, firms or ideas. This is the key to innovation.

1. Karaev, A., Koh, S. C. L. and Szamosi, L. T. (2007), “The Cluster Approach and SME Competitiveness: A Review”, Journal of Manufacturing Technology Management, Vol. 18, No. 7, p. 818-835.

2. Porter, M. E. (1998), “Clusters and the New Economics of Competition”, Harvard Business Review, November-December, p. 77-90.

More on Integration: How can it best support innovation?

The following video reiterates some of the important principles of integration that I discussed in an earlier post:

The video was created by members of the STIR (Socio-Technical Integration Reseach) program of the Consortium for Science, Policy, and Outcomes at Arizona State University. The video discusses successful examples of integrating humanism and social science within the laboratory setting, and points to examples where the presence of social scientists improved the processes and outcomes in their respective labs.

The video does a good job of illustrating how the presence of social scientists in laboratory settings has evolved, and continues to do so. In my experience, social science aspects of technical research can take many forms, and valuable integration of scientific research within the social context can take place outside the laboratory as well as inside. An open and flexible approach to each project as a unique opportunity for integration (by funding bodies, researchers, etc.) ensures that social science components are not constrained within the confines of tradition; and ultimately, that they have the freedom to pursue the most relevant research for the given project.

The Future of Medicine

The days of having a simple blood test and a routine check up in your GP’s office to go over your state of health are coming to an end. We are getting closer to a new (and improved) era of practicing medicine. The term “Personalized Medicine” is usually used to refer to this practice; I shouldn’t fail to say that not everyone loves this term! Most physicians would tell you that in their opinion the practice of medicine has always been personalized and that is true indeed. A more correct way of referring to this movement might be “Genomic Medicine” or a derivative thereof.  We are moving away from the traditional evidence-based medicine to one where a comprehensive analysis of the patient’s genome (the complete genetic material) will allow us to make accurate diagnoses and provide a tailor-made treatment for that individual. Currently, this type of data analysis is performed routinely in research labs around the world including our own BC Cancer Agency’s Genome Sciences Centre. The hope is to make this kind of diagnosis and treatment affordable and accessible to every patient in the near future. But of course there are obstacles and challenges to overcome including scientific, technological, social and moral issues.

Parallel to this notion of diagnosing patients and treating them on the molecular level is another, perhaps not completely separate, movement which takes on an even more proactive role. “P4 medicine”, a term coined by Dr. Leroy Hood, refers not to treating patients, but instead to using billions of data points from each individual in order to monitor their state of health rather than their disease status. This “Systems Medicine”, as it is called, will integrate information from all levels of biological structures, molecules, cells, organs, the organism and its environment, in order to make a judgment about the system’s state of health and provide suggestions on how to improve it. Hopefully, this will help anticipate and prevent diseases, lowering the cost of health care while increasing its quality.

For more information on P4 and personalized medicine, please refer to my blog at http://katayoonkasaian.wordpress.com/

Integration in Action: Intellectual Property & Regulations in Agricultural Genomics

Genome BC and Genome Canada fund numerous and diverse projects in health and agricultural genomics, and are committed to successfully integrating societal, economic, environmental, and ethical considerations where appropriate into their projects. To that end, Genome Canada-funded research proposals must in many cases include GE3LS components to consider those non-scientific aspects of scientific research.

I have had the pleasure of working for the past 18 months as a member of the GE3LS component of the Genome Canada-funded Genomics of Sunflower project, focusing primarily on legal regimes affecting the development and delivery of genomics-associated products. Our research has uncovered a vast array of regulatory regimes that affect the delivery of agricultural genomics products, the impact of which will often vary significantly depending on whether or not the product meets arbitrary standards of “genetic modification” unique to individual nations. In addition to mandatory regulatory scrutiny, there are numerous intellectual property choices available to developers instituted to stimulate innovation.

The Sunflower GE3LS team has a mandate to integrate, to the greatest extent possible, with the project’s scientific team. Through co-authorships with the project leader and close work with numerous individuals on the scientific team, the GE3LS team has made significant efforts in this area. These efforts crystallized on November 19, 2011, with a conference that gathered leading regulatory and IP commentators from around the world at UBC to discuss many of the complications identified in this policy space and discuss alternatives. Alternatives were discussed in the context of the development and delivery of socially beneficial agricultural products, a goal that becomes more pressing when food challenges and the impending threat of climate change are considered (see recent works by Matthew Rimmer, Jeremy de Beer on the subject).

The conference itself offered some scintillating discussion on intellectual property and regulatory issues, and the GE3LS team expects to publish a work on the proceedings of the conference, in the near future. But instead of delving into the substantive content discussed, I’d like to take the opportunity to briefly comment on the makeup of the conference and how we chose to approach our mandate of ‘integration’.

Our GE3LS team was faced with a slate of broad sociolegal questions, and we were delighted to assemble a conference team that included legal experts from around the globe, engaged participation from our scientific team and industry collaborators, economists, and sociological commentators. The resulting discussion was extremely fluid and touched on all aspects of this particularly broad problem (ie. how to facilitate developing and delivering socially beneficial agri-products), without becoming bogged down in technical details. This fluidity, and the agility with which a diverse group can approach eventual deliverables and recommendations, is a key aspect of integration in the GE3LS context.

Policy conferences are interesting and tricky animals. This is particularly the case when international politics are involved, but, even amongst academic policymakers, finding common ground can be difficult when broad issues such as the environment, trade policy, and innovation are considered. A reference to the widely panned climate change conference recently held in Durban, South Africa is unavoidable here. When such broad issues are being discussed, there is nothing to be gained from limiting the field of commentators to those of a particular background (or those of a particular political affiliation). In fact, without as diverse a commentating body as possible, that body may lose perspective, the downstream quality and originality of the discussion may suffer, and results may remain married to traditional approaches that have since gone the way of the dodo.

Six Environmentally Friendly Resolutions for Students in the Lab

Laboratory science is not the most environmentally friendly occupation. Although it is far more eco-friendly than drilling for oil, the large quantities of plastic waste generated and electricity consumed do not make for a small carbon foot print. Most of the waste generated is absolutely necessary to the research. Experiments need to be accurate; therefore much of the plastic used in laboratories cannot be reused for reasons of contamination. Cell culturing conditions need to be sterile, and all the equipment for those assays has to be autoclaved to prevent undesired microbial growth in culture flasks. Incubators need to be kept at constant temperatures at all times so that cultures are always growing in stable, reproducible conditions.
Of course, it’s not that scientists are unconscious of their environmental impact. Laboratory scientists, in my experience—keeping in mind that I go to grad school in Vancouver, a notoriously “hippie” city—are a very sustainably minded group of people. They generally agree that we should take steps proven to decrease the carbon levels in the atmosphere, since one cannot prove a negative (i.e. humans are not a causative force in global warming, or God does not exist), and that waiting for the evidence that human activity is a major contributor to the polar ice melting is a bad idea. They also certainly throw away a shoebox full of small plastic tips (i.e. pipette tips) a week, if they work in a life sciences lab.
By my (completely unscientific) estimation, 70% of all lab waste is inevitable. I am certainly not going to reuse my pipette tips, and I definitely am not going to volunteer to wash them. Even if I could get an undergrad to wash them, I would never use a used-then-washed pipette tip—I care about my experiments way too much for that. I will, however, make some changes to my lab routine to reduce my waste production and energy consumption.
In the spirit of the New Year, I propose a few environmentally friendly resolutions for everyone who works in a lab:
1) Plan you experiments out for the next few days and take stock of what you will need to autoclave. If it is reasonable, try to do all of your autoclaving for the week in one load, or ask you lab mates if they have something they also want to autoclave.
2) If you are pipetting multiple stock chemicals into a mix and sterility is not important, pipette the distilled, deionized water first and reuse that tip.
3) When you are able, wash and reuse your plastic conical tubes. Even better, hire an undergrad student to help with (read: do) this task.
4) Turn off equipment that is not currently in use.
5) Don’t leave the Bunsen burner flame going if you are going to step away from the sterile area, cap everything and relight it when you get back. Save gas, and your lab mate’s arm hair.
6) Walk up/down the stairs if you are not carrying heavy things, especially if you are on the second or third floors. Bonuses for you if you are on the fourth floor or higher, since this can also double as your “get more exercise” resolution.

Tell your Grandma about your research

Working on the issue of stem cells, I found that many people judge scientific procedures or methods without even knowing what they are good for and how its done. Or there are those that praise any kind of scientific work without questioning possible ethical aspects. Often, this is not because people are not interested or too lazy to get the information, it is that the information is badly distributed, explained and advertised throughout the media. Scientists also have problems to get their message across, which leaves ‘outsiders’ with little information that is often influenced by political goals or the type of media they consume.

This already starts in university when social scientists and researchers in labs stick to their own people, department and research field. Communication between them is rare and conferences on specific issues that address natural scientists OR social scientists do not encourage connections either. Also, both do not have to explain their research to people that are not affiliated with any university. This is especially true for PhD students who aim to stay in academics. One of my professors used to say: ‘Write and talk about your research as if you explain it to your Grandma’. Frankly, I do not think that my Grandma is interested in the research I am doing, but trying to rephrase a topic in that way is more challenging than one might think. At the same time no one wants an hour-long explanation of every detail. This is where the ‘elevator pitch’ comes in. It challenges anyone to summarize their idea and its value within a time frame of 30 seconds to two minutes (the time of an elevator ride).

To be able to explain research in a comprehensible and short fashion is crucial not only to connect to fellow researchers from other fields (and your Grandma), it also helps to get the message across to everyone who wants to understand where research is heading and how it benefits each and everyone. Most of the scientific discoveries will become more complicated and detailed and at the same time affect people in the way they for example receive health care, are treated for diseases or the medication they take. Showing the clear value of the research by making it accessible and understandable also enhances the chances of funding, that is when the government or government agencies can easily argue for the benefits of a certain project.

What do you think? Should researchers make more effort to explain their studies? Would you be able to summarize your research during an elevator ride with your Grandma?

Is my research relevant?

For a graduate student, September means both the return of undergrads to campus and deadlines for grant application – it also means the start of the rainy season in Vancouver, but that only means that I don’t have to feel like I’m wasting sunny Saturdays cooped up in the lab. Admittedly, neither of these things is something that we (i.e. the grad students) look forward to, despite once being undergrads ourselves, and liking being funded. This is because the sudden increase in campus population results in long wait times for everything from getting a treadmill at the gym to wireless connectivity, and writing grant applications results in a dramatic increase in white hair count, if you are lucky, and dramatic loss of hair, if you are not.

One of the most frustrating aspects of writing grant applications, beyond the given fact that one never has “enough” data, is explaining the relevancy of a project to a lay and general science audience. Science, of course, is always relevant in some way. Sir George Porter (winner of the 1967 Nobel Prize in Chemistry), in his paper The Relevance of Science, said that the true relevance of science was that it paved the way for “a new purpose for life, …through further knowledge and understanding of  nature?”(1)However, explaining why your science is more relevant than your colleagues’ represents a unique, hair rending challenge.

Science, by its nature, is predisposed to sounding dull. To be able to form a proper hypothesis – a question that is answerable by a yes or no, for example, ‘does histone H3 tail lysine acetylation cause the linker histone H1.5 to bind with less affinity to acetylated nucleosomes versus unacetylated nucleosomes?’ (one of my current research questions) – requires drilling down to minutia that only interests a couple dozen scientists in the world. Additionally, a good proportion of hypothesis driven research is what is called ‘blue skies’ or basic research, meaning research that doesn’t have immediately apparent relevance. Therefore, to actually write something into the box describing the relevance of a particular project requires ‘science extrapolation,’ or less generously ‘crystal ball science,’ which involves heavy usage of phrases such as ‘may result in,’ ‘potentially relevant to,’ and ‘has been implicated to be involved with.’

The world is complicated, and science projects have to be hyper focused to have any chance of proving progress in time for the next funding cycle. Despite science learning increasing faster than ever, big picture scientific progress can be measured in careers –when you account for all the tiny details leading up to the Eureka! moment. No mainstream-news worthy discovery could be made without tracing back a thousand small steps, which is one of the reasons why citations are so important in scientific writing. Science is like the Great Wall: an unbelievable undertaking made of millions of small pieces, for which thousands have devoted years of their lives.

From the outside, it appears dishonest for most scientists, outside of those working directly on post-basic therapeutic development, to say that they are working on a cure for X disease. But in a way we all are. Every discovery adds to the base of knowledge that will someday lead to that cure. Every science project, therefore, is relevant –despite being about the interaction of two proteins you didn’t even know existed in your body – and hopefully the granting agencies choose to fund you.

1.George Porter, “Relevance of Science”, Journal Amer. Sci. Affil., March 1976, p. 3.