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Patients take centre stage at US research institute
World Report
Patients take centre stage at US research institute The Patient-Centered Outcomes Research Institute seeks to involve patients with every aspect of clinical trials to ask and answer questions that they have about diseases. Carrie Arnold reports. Scientists studying a disease have a lot of questions that drive their work. They want to know what causes a disease, what proteins are involved, and the cellular pathways that can make a disease better—or worse. They ask about tiny changes to receptors on the outside of cells, wanting to know what molecules bind and when. They want to know whether they can develop medications that can treat the disease, or at least its symptoms, and then whether these drugs will prolong patients’ lives and reduce key symptoms. Patients with these diseases, however, often have very different questions. How will this disease affect my life or that of my child? What side-effects does drug treatment have? How do I choose between treatments? Physicians and scientists don’t always have answers for these types of questions, and agencies like the US National Institutes of Health don’t fund the types of studies that can help. Often, scientists don’t think about asking these types of questions because they often haven’t worked with patients to ask about their needs and concerns. For most of medicine’s history, this level of patient engagement simply wasn’t done, explains Joe Selby, executive director of the US Patient-Centered Outcomes Research Institute (PCORI). Selby says that the goal of PCORI is to change all that. “The name we were given caused us to rethink how we did research”, Selby says. “We want to fund research that patients say is important to them.” Buried deep in the Affordable Care Act of 2010 was a small section that created PCORI. The legislation set an aggressive timeline to get the Institute up and running. By September, 2010, the US Government Accountability 216
Office had selected PCORI’s board of directors, and, a year later, PCORI put out its first call for applications for pilot projects. For the biomedical research community, PCORI represents a fundamental shift in the way they do research. Although most, if not all, scientists have patient outcomes in mind as they work, they weren’t focusing on the outcomes important to patients. This shift can’t be understated, Selby said.
“‘We want to fund research that patients say is important to them.’” The Institute, whose offices are in Washington, DC, is funded by a small fee applied to many of the health insurance policies sold in America, usually around US$1 per plan. Since its inception, PCORI has funded 360 different research contracts in 39 states, totalling $671 million. Examples of some of the work that PCORI supports follows.
Better ways to treat pain For Beverly Thorn, a health psychologist at the University of Alabama, applying for PCORI funding seemed like a natural next step in her research. Thorn specialises in treating chronic pain using psychotherapeutic techniques, helping patients better cope with pain and focusing on what’s important to them. Many of Thorn’s patients are older, at or below the poverty line, have very low literacy skills, and attend government-funded clinics for their health care. She wanted to see whether the cognitive behavioural therapy (CBT) that had been developed for patients with pain would work in this particular population. Initially, some of the
employees at the clinics told Thorn that the study was pointless: these patients were only after drug treatment. But when she asked them, that’s not what she found. “The patients who came to me said they wanted to get off the medication, that they hated the way it made them feel”, Thorn said. This supported her belief that this group would be open to behavioural pain management. After completing a small pilot study that showed her CBT materials could be adapted for a low health literacy group, Thorn began a larger trial comparing CBT, pain education, and treatment-as-usual to see which would best help patients. All groups answered extensive questions about their personal, health, and pain histories. The two treatment arms consisted of 10 weeks of group therapy, and all groups were followed up for 6 months. Thorn had initially wanted to follow up the groups for 12 months, but conversations with patients convinced her to decrease follow-up time, after which the treatment-as-usual arm could participate in the CBT or pain education groups. The study, Thorn said, is currently half enrolled, and she is hoping to complete enrolment in the next year. So far, the response from patients has been positively enthusiastic. “They still have pain at the end of treatment, but they approach their pain in a totally different way. One patient said, ‘I still have pain, but pain doesn’t have me.’”
Solving side-effects When a child is diagnosed with epilepsy, parents generally have two major questions, says PCORI scientist David Loring, a neuropsychologist at the Emory University School of Medicine, GA, USA. “They want to know how the diagnosis will affect www.thelancet.com Vol 385 January 17, 2015
their child, and they want to know how the medications will affect their child.” Loring realised that scientists hadn’t yet answered the second question. Many of the anti-seizure drugs currently on the market are equally effective at preventing seizures, but also have substantial side-effects that can prevent a person from being able to take the drug, as well as interfere with the development and education of young children. Epileptologists had no information to give parents about which drug would be least likely to cause side-effects in their children. With the help of PCORI and his colleagues at Emory, Loring decided to investigate side-effect profiles of anti-seizure medications to help parents make better-informed decisions about their child’s epilepsy treatments. He is enrolling 300 children between the ages of 6 and 12 years with location-related epilepsy and randomly assigning them to one of three commonly used anti-seizure drugs: levetiracetam, lamotrigine, or oxcarbazepine. They will receive a battery of neurocognitive tests at baseline, and at 3 and 6 months. Loring hopes to discover not just which drugs cause which side-effects, but also figure out if certain groups of children are more likely to experience them. It’s data that many epileptologists wish they had. “Epileptologists acknowledge that they don’t have any data on side-effects, and this information would affect which drugs they prescribe”, Loring said.
Deciding on dialysis Around one in ten American adults has some type of chronic kidney disease, and more than 871 000 are being treated for end-stage renal disease. Two types of dialysis—haemodialysis and peritoneal dialysis—do the normal jobs of the kidney by eliminating excess water from the blood and removing waste. Patients undergoing haemodialysis attend a treatment www.thelancet.com Vol 385 January 17, 2015
facility at least three times per week for 5–6 hours at a time. Peritoneal dialysis can be done at home each and every night. Nephrologist Francesca Tentori of Arbor Health in Michigan says that physicians usually offer a choice between these two options to their patients, leaving the final choice up to the patients. Although both types of dialysis do the same function, they have very different effects on a patient’s life. Peritoneal dialysis can be more flexible, but it requires that the patient be committed to daily treatments. Haemodialysis, on the other hand, can be administered by medical professionals but requires a massive time commitment. For Tentori, it was a “natural choice” to seek funding from PCORI to try to help patients decide between these two methods. “Physicians are biased—we tend to prioritise survival over everything. And while patients value this too, there are a lot more facets to it that we hadn’t seen”, Tentori said.
“‘Physicians are biased—we tend to prioritise survival over everything. And while patients value this too, there are a lot more facets to it that we hadn’t seen’...” Tentori and colleagues began by assembling a panel of patients that included diversity in age, sex, occupation, and race to help develop the study. They began interviewing 170 patients with kidney disease currently receiving dialysis to develop a lengthy, structured questionnaire that they intend to administer to more than 7000 other patients receiving dialysis to figure out how the different treatments affect all aspects of their lives. The ultimate goal is to use these answers to create an interactive web tool that will enable patients to process information and choose the treatment that is best for them. “This is a choice that will affect the rest of their lives”, she said.
Ken Welsh/Design Pics/Corbis
World Report
One PCORI scientist is working to help patients decide between types of dialysis
Options for uterine fibroids Several years ago, the Agency for Healthcare Research and Quality (AHRQ) asked Evan Myers, an obstetrician/gynaecologist and epidemiologist at Duke University, NC, USA, to review the management options for women with uterine fibroids. “Basically, we found that no one knew anything”, Myers said. He said that historically, it had been hard to get women to participate in randomised controlled trials when hysterectomy was an option, which limited the information that scientists had. As part of the AHRQ study, Myers had talked with patients, insurance companies, and physicians—exactly the combination that PCORI was looking for in their studies. So Myers applied for PCORI funding to study several different fibroid treatment options at nine geographically diverse treatment sites. Based on patient input, Myers and colleagues intend to answer three basic questions: which of the available treatments do the best job at relieving symptoms of fibroids? Which do the best at preserving reproductive function? Which treatments work best in different subpopulations? Then, the researchers will develop treatment recommendations that patients will easily be able to access. “Patients want the best possible answers, and this is a way to give these to them”, Myers said.
Carrie Arnold 217
Patients take centre stage at US research institute The Patient-Centered Outcomes Research Institute seeks to involve patients with every aspect of clinical trials to ask and answer questions that they have about diseases. Carrie Arnold reports. Scientists studying a disease have a lot of questions that drive their work. They want to know what causes a disease, what proteins are involved, and the cellular pathways that can make a disease better—or worse. They ask about tiny changes to receptors on the outside of cells, wanting to know what molecules bind and when. They want to know whether they can develop medications that can treat the disease, or at least its symptoms, and then whether these drugs will prolong patients’ lives and reduce key symptoms. Patients with these diseases, however, often have very different questions. How will this disease affect my life or that of my child? What side-effects does drug treatment have? How do I choose between treatments? Physicians and scientists don’t always have answers for these types of questions, and agencies like the US National Institutes of Health don’t fund the types of studies that can help. Often, scientists don’t think about asking these types of questions because they often haven’t worked with patients to ask about their needs and concerns. For most of medicine’s history, this level of patient engagement simply wasn’t done, explains Joe Selby, executive director of the US Patient-Centered Outcomes Research Institute (PCORI). Selby says that the goal of PCORI is to change all that. “The name we were given caused us to rethink how we did research”, Selby says. “We want to fund research that patients say is important to them.” Buried deep in the Affordable Care Act of 2010 was a small section that created PCORI. The legislation set an aggressive timeline to get the Institute up and running. By September, 2010, the US Government Accountability 216
Office had selected PCORI’s board of directors, and, a year later, PCORI put out its first call for applications for pilot projects. For the biomedical research community, PCORI represents a fundamental shift in the way they do research. Although most, if not all, scientists have patient outcomes in mind as they work, they weren’t focusing on the outcomes important to patients. This shift can’t be understated, Selby said.
“‘We want to fund research that patients say is important to them.’” The Institute, whose offices are in Washington, DC, is funded by a small fee applied to many of the health insurance policies sold in America, usually around US$1 per plan. Since its inception, PCORI has funded 360 different research contracts in 39 states, totalling $671 million. Examples of some of the work that PCORI supports follows.
Better ways to treat pain For Beverly Thorn, a health psychologist at the University of Alabama, applying for PCORI funding seemed like a natural next step in her research. Thorn specialises in treating chronic pain using psychotherapeutic techniques, helping patients better cope with pain and focusing on what’s important to them. Many of Thorn’s patients are older, at or below the poverty line, have very low literacy skills, and attend government-funded clinics for their health care. She wanted to see whether the cognitive behavioural therapy (CBT) that had been developed for patients with pain would work in this particular population. Initially, some of the
employees at the clinics told Thorn that the study was pointless: these patients were only after drug treatment. But when she asked them, that’s not what she found. “The patients who came to me said they wanted to get off the medication, that they hated the way it made them feel”, Thorn said. This supported her belief that this group would be open to behavioural pain management. After completing a small pilot study that showed her CBT materials could be adapted for a low health literacy group, Thorn began a larger trial comparing CBT, pain education, and treatment-as-usual to see which would best help patients. All groups answered extensive questions about their personal, health, and pain histories. The two treatment arms consisted of 10 weeks of group therapy, and all groups were followed up for 6 months. Thorn had initially wanted to follow up the groups for 12 months, but conversations with patients convinced her to decrease follow-up time, after which the treatment-as-usual arm could participate in the CBT or pain education groups. The study, Thorn said, is currently half enrolled, and she is hoping to complete enrolment in the next year. So far, the response from patients has been positively enthusiastic. “They still have pain at the end of treatment, but they approach their pain in a totally different way. One patient said, ‘I still have pain, but pain doesn’t have me.’”
Solving side-effects When a child is diagnosed with epilepsy, parents generally have two major questions, says PCORI scientist David Loring, a neuropsychologist at the Emory University School of Medicine, GA, USA. “They want to know how the diagnosis will affect www.thelancet.com Vol 385 January 17, 2015
their child, and they want to know how the medications will affect their child.” Loring realised that scientists hadn’t yet answered the second question. Many of the anti-seizure drugs currently on the market are equally effective at preventing seizures, but also have substantial side-effects that can prevent a person from being able to take the drug, as well as interfere with the development and education of young children. Epileptologists had no information to give parents about which drug would be least likely to cause side-effects in their children. With the help of PCORI and his colleagues at Emory, Loring decided to investigate side-effect profiles of anti-seizure medications to help parents make better-informed decisions about their child’s epilepsy treatments. He is enrolling 300 children between the ages of 6 and 12 years with location-related epilepsy and randomly assigning them to one of three commonly used anti-seizure drugs: levetiracetam, lamotrigine, or oxcarbazepine. They will receive a battery of neurocognitive tests at baseline, and at 3 and 6 months. Loring hopes to discover not just which drugs cause which side-effects, but also figure out if certain groups of children are more likely to experience them. It’s data that many epileptologists wish they had. “Epileptologists acknowledge that they don’t have any data on side-effects, and this information would affect which drugs they prescribe”, Loring said.
Deciding on dialysis Around one in ten American adults has some type of chronic kidney disease, and more than 871 000 are being treated for end-stage renal disease. Two types of dialysis—haemodialysis and peritoneal dialysis—do the normal jobs of the kidney by eliminating excess water from the blood and removing waste. Patients undergoing haemodialysis attend a treatment www.thelancet.com Vol 385 January 17, 2015
facility at least three times per week for 5–6 hours at a time. Peritoneal dialysis can be done at home each and every night. Nephrologist Francesca Tentori of Arbor Health in Michigan says that physicians usually offer a choice between these two options to their patients, leaving the final choice up to the patients. Although both types of dialysis do the same function, they have very different effects on a patient’s life. Peritoneal dialysis can be more flexible, but it requires that the patient be committed to daily treatments. Haemodialysis, on the other hand, can be administered by medical professionals but requires a massive time commitment. For Tentori, it was a “natural choice” to seek funding from PCORI to try to help patients decide between these two methods. “Physicians are biased—we tend to prioritise survival over everything. And while patients value this too, there are a lot more facets to it that we hadn’t seen”, Tentori said.
“‘Physicians are biased—we tend to prioritise survival over everything. And while patients value this too, there are a lot more facets to it that we hadn’t seen’...” Tentori and colleagues began by assembling a panel of patients that included diversity in age, sex, occupation, and race to help develop the study. They began interviewing 170 patients with kidney disease currently receiving dialysis to develop a lengthy, structured questionnaire that they intend to administer to more than 7000 other patients receiving dialysis to figure out how the different treatments affect all aspects of their lives. The ultimate goal is to use these answers to create an interactive web tool that will enable patients to process information and choose the treatment that is best for them. “This is a choice that will affect the rest of their lives”, she said.
Ken Welsh/Design Pics/Corbis
World Report
One PCORI scientist is working to help patients decide between types of dialysis
Options for uterine fibroids Several years ago, the Agency for Healthcare Research and Quality (AHRQ) asked Evan Myers, an obstetrician/gynaecologist and epidemiologist at Duke University, NC, USA, to review the management options for women with uterine fibroids. “Basically, we found that no one knew anything”, Myers said. He said that historically, it had been hard to get women to participate in randomised controlled trials when hysterectomy was an option, which limited the information that scientists had. As part of the AHRQ study, Myers had talked with patients, insurance companies, and physicians—exactly the combination that PCORI was looking for in their studies. So Myers applied for PCORI funding to study several different fibroid treatment options at nine geographically diverse treatment sites. Based on patient input, Myers and colleagues intend to answer three basic questions: which of the available treatments do the best job at relieving symptoms of fibroids? Which do the best at preserving reproductive function? Which treatments work best in different subpopulations? Then, the researchers will develop treatment recommendations that patients will easily be able to access. “Patients want the best possible answers, and this is a way to give these to them”, Myers said.
Carrie Arnold 217