CTSI Blogs
The Research Ethics Blog by Bernard Lo, MD
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What Would You Recommend? - Case 2: Placebo Controlled Trials for Osteoporosis in Women
Two recent well-designed randomized controlled trials (RCTs) showed that two new agents, 1) lasofoxifene, a selective estrogen-receptor modulator, and 2) denosumab, a monoclonal antibody that inhibits osteoclasts, prevented fractures in women with osteoporosis. The RCTs compared the new agent vs. placebo added to calcium + vitamin D. However, other therapies are known reduce the incidence of fractures by 30%-50% compared to calcium + vitamin D.
Placebo controlled trials for osteoporosis have been controversial when effective therapies exist. Such trials are clearly unethical if participants are at risk for serious harm or if they do not give informed consent.
What Would You Recommend? - Case 1: Clinical Trials Involving Pregnant Women
During the 2009 H1N1 influenza pandemic, pregnant women had higher complication rates. It is hypothesized that this might be because standard doses of oseltamivir, the recommended treatment for the prevention and treatment of H1N1, are inadequate during pregnancy because of changes in renal and hepatic function and drug volume of distribution. More generally, over 50% of pregnant women take prescription drugs. However, evidence of safety and efficacy of drugs in pregnancy is weak, placing pregnant women and the fetuses at risk.
Carrying out clinical trials of drugs administered to pregnant women who is carrying the fetus to term is ethically sensitive both because of concerns about birth defects in the developing fetus and also because the fetus cannot consent to be a research subject.
Interpreting Federal Regulations on Human Participants Research: A Discussion with Students on Unresolved Ethical Issues
I posted a series of cases that highlight challenges scientists face when conducting research with human participants.
To receive credit for the final project in the Responsible Conduct of Research course I invite students to comment on those or other cases on this blog. Add your comments under the case they pertain to. A thoughtful paragraph will suffice.
A Biobank for Genomics Research: Do we need Patient Consent?
To facilitate clinical research, Vanderbilt University has constructed a biobank that contains DNA specimens derived from leftover blood remaining after clinical tests have been carried out, together with information extracted from the electronic medical record. The blood would be discarded if not used for research. All information is de-identified by the biobank before it is provided to researchers. See article.
The Vanderbilt IRB has determined that because researchers receive only de-identified information, specific projects carried out with biobank data and materials are not human subjects research, and therefore no consent is required.
Research with Existing Data and Specimens: What if Participants Object?
The Havasupai, a Native American tribe living near the Grand Canyon, have a very high prevalence of 
diabetes. Researchers collected blood samples and clinical data from 200 tribal members. Discussions with the tribe focused on research with diabetes, but the consent form allowed the study “the causes of behavioral/medical disorders.”
The researchers carried out a number of studies, including three genetic studies that tribe members found objectionable: on schizophrenia, on inbreeding, and on the evolution of populations. The tribe regarded the first two studies as stigmatizing, and the latter study contradicted the tribe’s beliefs about their ancestry. The tribe and individual donors of materials brought a lawsuit.
Research Misconduct: A Case of Monkey Business
Marc Hauser is an academic superstar at Harvard who has carried out research on the evolutionary basis of human cognition and morality and on the cognitive abilities of primates. He has also written best-selling popular books about his field. Three years ago, a research assistant and graduate student in his laboratory raised allegations of misconduct, accusing him of reporting findings on videotapes that could not be confirmed by other observers. One study reported that tamarin monkeys can recognize themselves in a mirror. Another professor in the field who reviewed the videotapes of the experiment said that there was no basis for that conclusion. Another study claimed that tamarin monkeys could learn moral rules just as human infants can. A co-author on the latter study said that he saw summaries of the data but not the raw data. This month, Harvard found Hauser guilty of 8 instances of scientific misconduct but gave no details, citing confidentiality concerns.
Genomic Sequencing: Identifying the Anonymous
Law and Order. CSI. N.C.I.S. Who hasn’t watched a crime investigation show on TV? A detective finds a tiny sample blood at a crime scene. Just before a commercial break, the team runs a DNA analysis on the computer and submits the results to the national database. We all know what happens next – after the commercial, the computer identifies a suspect.
Re-identification of anonymous specimens makes for great TV drama, but there are some disturbing implications for the confidentiality of genomic sequencing data in biomedical research once it becomes feasible to sequence a person’s entire DNA sequence at moderate expense.
Protecting Participants in Clinical Trials
Meta-analyses of clinical trials of antidepressants have found a trend towards increased suicidality in children and adolescents receiving selective serotonin reuptake inhibitors (SSRIs). These meta-analyses raised concerns about conflicts of interest because published trials showed that the drugs were effective and safe in these circumstances, but when unpublished studies carried out by the manufacturers were also considered, the drugs were shown to be ineffective and possibly unsafe. The report Conflict of Interest in Medical Research, Education, and Practice provides other examples of failure to publish negative results or serious adverse events in industry-sponsored clinical trials. See summary (PDF 304KB). Here we discuss another ethical issue: How to protect participants in clinical trials if their condition worsens?
When Authorship Turns Sour
A friend e-mailed me about a difficult authorship dispute he was having – a research collaboration gone sour. Being an author on a paper in a major journal can provide tremendous satisfaction and prestige, but authorship can also produce painful disputes over responsibilities and positions in the list of authors. Dilemmas over authorship are common, can cause great emotional pain, and require huge time commitments. Imagine such a situation: A group of investigators has completed a project on a predictive model of genotyping cancer specimens.
Placebo Controls – Are they Ethically Acceptable in a Clinical Trial?
Every intern learns how to manage patients with massive upper GI bleeds: start two large-bore IVs and fluid resuscitation, send a clot to type and cross packed RBCs, call GI consult. Another component of this usual care is administration of proton-pump inhibitors. Evaluating the effectiveness of proton-pump inhibitors in GI bleeding is challenging because they are widely used in this condition.