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Disclosures

None of the faculty, planners, speakers, providers nor CME committee have any relevant financial relationships with commercial interest Organizing and Participating There is no commercial support for this CME activity in a Research Project

NOVEMBER 18, 2014

David D. Lo, MD, PhD Distinguished Professor, Biomedical Sciences Senior Associate Dean, Research UCR School of Medicine

Introduction to This Series Today’s Discussion

• Our initial series will have four topics: • Organizing and Participating in a Research Project • Asking Research Questions in a Clinical Setting • Getting involved in research questions at any level • How does scientific method apply in the clinic • Organizing and Participating in a Research Project • Getting involved in research questions at any level • Today we will discuss research settings at UCR and UCR SOM • It Doesn’t Count Until It’s Reported: Presenting, Publishing and ways you can get involved and Grant Writing • Effective communication of scientific questions and • We will also have a discussion on experimental design answers to all audiences issues, especially logical • Research Ethics (Why do we do research?), and IRB approval • Human curiosity, the motivations to do research, and ways to guide proper conduct of research

Visiting a Foreign Culture: Visiting a Foreign Culture: The Biomedical Research Laboratory The Biomedical Research Laboratory

• Travel broadens the mind: Learn a new language and culture! • Travel broadens the mind: Learn a new language and culture! • How does Biomedical research compare to clinical practice? • How does Biomedical research compare to clinical practice? • We wear Personal Protective Equipment (PPE): • We wear Personal Protective Equipment (PPE):

Or depending on the safety level…

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Visiting a Foreign Culture: How is the conventional research lab different The Biomedical Research Laboratory from the usual clinical practice? Clinical Research • How is the conventional research lab similar to the • Work product: Patient care • Research papers – publish or usual clinical practice? perish! • Hierarchy: Leadership down to specialized staff • Business model: Revenue from • Investigator-initiated Grant patient visits, procedures Awards (NIH, Industry) • Management of staff at different levels • Job security, advancement: • Publications, grants, service, • Sophisticated (and expensive) equipment Clinical work, GME, Board invited seminars, committees, • Choices in investment certification conference organization, (teach) • Teaching: Medical students, • Postdocs, Graduate students, • Administrative infrastructure: pay the bills, Residents Undergrad (mostly pre- compliance • Train the next generation of meds!!) CLINICANS • The emphasis is on training RESEARCHERS So the emphasis is different

So What Occupies Faculty Actual Time Sidebar: versus Faculty Preoccupation? Why the preoccupation with grants?

• NIH Funding has not been on a good trend lately • After a doubling of funding from the late 1990s to 2003, NIH funding has essentially undergone an “undoubling”

• What does this do to • Research and FUNDING, especially FUNDING research motivations • In some institutions, faculty salary depends on extramural or incentives? research funds, so the pressure can be intense

Back to Research: Assisting in a clinical study or clinical trial if your clinical Types of Research Settings site is involved in the study

• At UCR and UCR SOM, you do not have to initiate your own • Clinical studies are often performed at multiple sites. At each study to be involved in research. You may be able to work site, patients must be recruited, enrollment criteria are use to with researchers in at least three different settings: decide who can be entered into a study, and then the subjects are followed • Assisting in a clinical study or clinical trial if your clinical site is • Studies may be supported by drug companies or can be involved in the study funded by agencies such as the NIH (investigator-initiated) • Working with basic biomedical researchers by providing • Strict rules govern the performance of these studies to access to clinical biopsy specimens protect the patients as well as insure the quality of the data • Collaborating with a UCR social sciences researcher by generated in the study helping provide access to clinical populations for a study • Some studies involve medical interventions or drugs, so there can be risk to the subjects, and so close monitoring is involved • Training of medical staff is essential to be certain that protocols are strictly followed

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Working with basic Biomedical researchers by providing Collaborating with a UCR social sciences researcher by access to clinical biopsy specimens helping provide access to clinical populations

• Biomedical Sciences research labs generally do research with • Several social sciences faculty at UCR are working on various animal models of disease (mainly mouse models, but also rats, aspects of clinical medicine, including topics on doctor-patient non-human primates, etc.) Predictions made in animal models interactions, to resource management and outcomes require confirmation using clinical samples • Examples: • Examples: • A Psychology faculty researcher has been studying affective • In a study on cytokine production and macrophage behavior among cancer patients. How is behavior influenced activation in a mouse model of parasite infection, one of by anticipation of a potentially life-changing diagnosis? our faculty worked with a doctor in Africa to supply serum samples from patients including control and parasite • A faculty researcher in Economics has been studying the infected patients. They found that infected serum value of committing significant resources to neonatal intensive contained higher levels of a specific cytokine. care units. Are the resources optimally utilized, and is there evidence that it has a beneficial effect on birth outcomes? • In a study on the effects of intestinal inflammation and epithelium barrier function, intestinal biopsy samples from • A faculty researcher in Political Sciences studies the role of the control and IBD patients will be needed to confirm the internet in patient access to correct health information effects seen in a mouse model of colitis.

Example: Surgical Communication Surgical Communication (cont.) (Kate Sweeny, UCR Psychology)

• Important but rarely studied (most research in • One earlier study audio-recorded conversations primary care). with surgeons (orthopedics and general). • Particularly difficult due to complex and technical • Surgeons did most of the talking discussions about procedures, risks, etc. • Few open-ended questions • Focused on biomedical (not psychosocial) • Patients generally dissatisfied with surgeons’ • Good start, but some limitations… communication in outpatient setting (1 study). • ≈90% White/Non-Hispanic, all English fluent • Brevity of conversation • Most patients had seen surgeon before • Lack of opportunity for participation in decisions • Unusually long conversations (M = 13 min.)

Questions Questions

• How do patients feel about their surgical care? • What predicts surgical outcomes? • Satisfaction, adherence intentions • Adherence, success, satisfaction • Predictors related to condition and care • Predictors related to condition and • Are there disparities in patients’ experiences? • Predictors related to patients’ state of mind • Predictors related to • Are there disparities in patients’ outcomes following surgery? • Predictors related to

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Still Other Alternatives, for example: Summary Bioengineering Senior Design

• Experiences with surgical care are a function of… • Students in the last year of the undergraduate bioengineering • Demographic differences (disparities…?) program work in small groups (4-5 each) to design, prototype, and test a project over the academic year • Their health condition (severity, general health) • Past projects have included: • The surgeon’s style of care (emotions, control, • A pediatric laparoscopic surgical respect, comprehension, conversational goals) simulator for duodenal atresia • The patient’s state of mind (hope, satisfaction) • The Diaper Detective (won 3rd place in NIH DEBUT, • Up next: Recordings of patient-surgeon interactions! https://www.youtube.com/watch?v=VzFio1Wfwe0 ) • Characteristics of surgical communication • Groups are strongly encouraged to enter both the BME Start • Communication about expectations and NIH DEBUT competitions, which value clinically motivated projects with potential business value Additional note: see how physicians can be • At least two meetings with a group per academic quarter involved at multiple points in this kind of study • Please contact [email protected]

Still More Alternatives, for example: SOM LACE PIP Example SOM LACE Practice Improvement Project

Example of • UCR SOM Medical Students first three years includes an student project outpatient contact experience • As part of this experience, students also develop projects with volunteer clinical faculty to improve a specific aspect of clinical practice: Practice Improvement Project (PIP) • Projects may include any aspect of clinical practice from diagnostic methods, patient interaction, etc. • Projects are proposed with implementation plan, and evaluation of outcomes • Students do a PIP project each year • Contact: Michael Nduati ([email protected])

What If You Want To Try Your Own Idea? Steps To Starting A Research Project

• Is “Protected Time” required? A complicated question • Two discussions here: • For many clinical positions, it is expected that some of the compensated time is to be spent doing teaching and • How do you get an actual research project “scholarly activity” approved, funded, and started? • This is usually not counted as “protected time” and is part of the job description • “Scholarly activity” is not necessarily the same as doing original research • How do you put together a research idea and • In some cases, a position can have a portion set aside for a design the experimental approach? specific job separate from clinical duties, such as research • This time is paid from different funds, such as revenue from extramural funding (e.g., NIH research grant) • So, “Research” can be done in any setting, whether as part of clinical/teaching/scholarly activity, or as dedicated time

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Steps To Starting A Research Project Steps To Starting A Research Project

• Finding collaborators Some comments on getting approval for your project: • As already discussed a few slides back •In some institutions, there is an institutional Human Subjects Institutional Review Board (IRB) that reviews protocols • Getting approval • Any research involving human subjects must have a • Defining and describing the project (discussed below) protocol reviewed and approved by an IRB • Department approval – does it affect ongoing • Larger institutions such as UCR has internal IRBs, and medical responsibilities? schools often have several IRBs to cover all of the research protocols needing review • Human Subjects Protocol • (We’ll discuss protocols, training, and IRB review later) • Institutional Review Board review • However, not all hospitals or clinics have their own IRB • In some cases, protocols can be sent out for external • Getting support or extramural funding review by contract organizations such as Western IRB • For the next seminar • In other cases, protocols can be reviewed by institutions under inter-institutional agreements (MOUs).

Experimental design Experimental design

• A topic too big for a single talk, but a few things to mention: • Hypothesis: “all patient-doctor communication is viewed through • The best studies are focused on a specific question, a gender-based filter” • As discussed last time, good questions test a hypothesis • “Mechanism” is that communication is biased by gender- • So how do you get your starting hypothesis? specific roles and hierarchies, and that these influences dominate other aspects of communication • Begin with general observations, and a literature search • So how do you test that? Set up a test that challenges this • Your hypothesis might already be part of the discussion or you mechanism can come up with your own new hypothesis • Maybe by setting up contrasting settings where gender is • Ideally, the hypothesis is based in a mechanism, even if it obvious versus settings where gender is ambiguous but use involves something less concrete such as behavior the same scripted discussion • For example, one might propose that “all patient-doctor • Set up a quantitative measure for the interaction, so that the communication is viewed through a gender-based filter” – presence of bias can be detected (I didn’t way it was going that is, the “mechanism” here is that communication is to always be easy!) biased by gender-specific roles and hierarchies, and that these influences dominate other aspects of communication

“Translational” Is Where It’s At Final Vignettes: Logical Fallacies

• What kinds of hypotheses and tests are more interesting? • Logical Fallacies are traps that we fall into because • There are the ongoing controversial issues in medical we rely so often on quick judgment and intuition practice – “why do we do this?” • There are the topics that are most likely to be reported on • Such fallacies may come from personal popular media, such as CNN experiences and might in some cases lead to • There are the topics that are most likely to influence correct conclusions even though the logical route medical practice, medical economics, etc. to that conclusion is wrong • Logical fallacies are dangerous in clinical research • “Translational” topics are those that are more likely to affect settings because they impede new knowledge in medical practice, access to health care, healthy behaviors areas where conventional wisdom is wrong • Could be development of a drug making it to the clinic • Guarding against such logical traps depends in • Could be a new method of diagnosis part on recognizing these traps • Could be a new way to bill for care

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Recognize that error? Some Types of Logical Fallacies

• Formal fallacies – basically types of non sequiturs • Appeal to probability: (just because it might, then it will) “It could happen”

• Argument from : Just because an argument is flawed, doesn’t mean the conclusion is wrong “He said that the asteroid can’t hit us because the atmosphere protects us from everything”

Some Types of Logical Fallacies Some Types of Logical Fallacies

• Informal fallacies – problems with use of evidence • • Faulty generalizations – weak premises “It must be true because we have no counter evidence” • • “”/ “” – a generalization held true by ruling “Since we assume that the hypothesis must be at least partly true, out counterexamples on shaky grounds then these other parts should turn out to be true” • •“Since we know that cytokines regulate cell differentiation, then “I like this data because it makes my case” this tissue pattern must be regulated by cytokines.” • Hasty generalization • Correlation does not imply causation “This one protein has kinase activity, so all proteins must be “They are found together, so X must cause Y” (not Y causing X?) kinases” •“The gene array always shows these genes going up together, so this gene must regulate the other” • /hypostatization “There’s got to be a mechanism that does this thing, so let’s assume it’s there”

Some Types of Logical Fallacies Some Types of Logical Fallacies

• fallacy –“do what I say, • Conditional fallacies – underplays/overplays logical not what I mean” extremes • : “And you’re ugly too” • , Reductio ad absurdam • “You’re just an immunologist, so you can’t possibly “But that couldn’t work, or all cells will undergo apoptosis understand cell biology” automatically” • : Threat - “You have to agree if you • “This receptor can’t be related to the innate immune want to get your PhD/published/funded” signaling pathway, or it would always trigger • (closely related to Appeal to Authority – “Because I’m the inflammation and tissue destruction” Chair and I say so”; often associated with Nobel Laureates) • Black swan blindness – ignores low probability but high • : “We’ve got to be right because it would impact events be completely novel!!” “I’ve never seen those kinds of things happening before so • “We don’t understand how this metabolic pathway works, it can’t be real” so it must be something nobody has ever suspected • “The anti-inflammatory action of this drug must be from before” blocking COX2, since we don’t know of any other activity”

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A Few Other Errors In Science Practice Final Comments

• Phenomenon and observation is not hypothesis or mechanism • There are many types of clinically relevant and important research available • A “Fishing Expedition” • This includes connecting with researchers in Biomedical • The research labs, Social Sciences, Medical Economics, Medical School Practice Improvement Projects, Bioengineering • A Sham Argument set up be easily defeated; not • Your colleagues already did the hard work a great substitute for a strong hypothesis or test • There are many ways to initiate your own research project • Expectation is not proof • Not all require big budget research grants • cannot take the place of actual • But any research involving humans requires protocol data or evidence development, review, and approval • “In my series/ In my experience” • The best research asks useful and important questions for which people actually care about the answers • Insufficient sample size can lead to wrong conclusions from inadequate data

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