Life Science Compliance Update

May 05, 2014

PCORI Looks to Link Millions of Electronic Medical Records by September 2015

The Affordable Care Act generated more than the health exchanges and our favorite Sunshine Act. The law also created the Patient-Centered Outcomes Research Institute (PCORI), tasked with launching and coordinating comparative clinical effectiveness research (CER) – to find out which drugs, devices, and treatment options are more effective than others. PCORI recently began an 18-month project which aims to link together a network of millions of patients' medical records. Researchers could glean valuable information on comparative effectiveness from the data.

PCORI's vision, entitled PCORnet: The National Patient Centered Clinical Research Network, involves a "large, highly representative, national network for conducting clinical outcomes research." Importantly, the network would "foster a range of observational and experimental CER by establishing a resource of clinical data gathered in 'real-time' and in 'real-world' settings, such as clinics."

The Washington Post recently highlighted the progress PCORI has made, along with the challenges ahead. The Post notes that "government-funded scientists have begun collecting and connecting together terabytes of patient medical records in what may be one of the most radical projects in health care ever attempted." The researchers are collecting information on patients' diagnoses and conditions, results of blood tests, X-rays, MRI scans, as well as information on surgeries, insurance claims, and even links to genetic samples. "Nothing of this scale has been built before," the Post reports, "and researchers say the potential of the network to speed up research efforts and to answer questions that have long vexed scientists cannot be overstated."

Currently, clinical studies are very narrow in focus. "Physicians have long grumbled that few studies can be translated into practical advice," states the Post. "Some studies are too small to draw any definitive conclusions. Others include patients diagnosed with a single condition, while most patients are more complicated — they suffer from multiple issues. It isn't uncommon for studies to contradict each other, and there's no way for clinicians to know which one is right, because they often use different methodologies."

The Post also interviewed Francis S. Collins, director of the National Institutes of Health (NIH), who noted that time consuming nature of the randomized trials the NIH typically supports. "[Y]ou have to enroll patients from the very beginning, and that's a big infrastructure-building process that can take quite some time. And once a trial has been conducted, the whole thing has to be taken down again," Collins said. "It's a great way to answer one specific question, but it's not an efficient way to ask lots of questions."

On April 17, shortly after the Washington Post article, Joe Selby, Executive Director of PCORI, provided an update on PCORnet:

"[V[ast amounts of valuable health information are created every day during patients' interactions with clinicians, healthcare systems, and one another. The data generated through these real-world patient experiences are really the best way to find out what works best for patients in typical clinical care, given their individual circumstances and needs.

Opportunities to use this kind of health information are often missed, however. Most patients receive their care in more than one system. What's more, the individual systems have lacked efficient ways to communicate or collaborate with each other; this impedes comprehensive follow-up as well as research. Finally, single systems usually can't conduct studies that are large enough to provide reliable answers about what works for individual patients.

PCORnet is designed to address these issues. By integrating 18 Patient-Powered Research Networks and 11 health system–based Clinical Data Research Networks, it will facilitate the use of both patient-provided information and clinically derived data to support research. By folding research activities into clinical practice without interrupting the flow of care, PCORnet aims to facilitate comparative clinical effectiveness research and other kinds of studies on topics and questions most relevant to the needs of patients and those who care for them. The result will be a system that will enable researchers to ask clinical questions and derive results quickly and efficiently."

As Selby noted, 29 health data networks across the country are going in on the effort, 11 clinical data research networks and 18 patient powered research networks. View the lists here.

Anyone who has spent time in healthcare policy knows that a network of medical data covering millions of American patients raises some issues. Namely, critics have voiced concerns over patient privacy, questions of who would own and control the data, and how research would be prioritized.

According to PCORI's website, "Data will be collected and stored in standardized, interoperable formats under rigorous security protocols, and data sharing across the network will be accomplished using a variety of methods that ensure confidentiality by preventing patient identification."

Selby also addressed this challenge.

"Of course, it will take significant work to connect PCORnet's 29 individual health data networks, with coverage spanning the entire country, and develop the structures, governance, and policies to ensure that the national network they form operates smoothly and securely," he notes. "But building and leveraging the power of a large clinical data network and ensuring the security and privacy of sensitive personal information aren't mutually exclusive."

Selby states that "the need to provide robust data security measures and policies and procedures to guard patient privacy" is PCORI's chief concern. The 29 partner networks "will have their own governance systems and maintain their own data, which will be securely protected by a firewall. Each partner network will develop security measures, policies, and procedures that are right for its members, as we develop general policies that will apply to PCORnet as a whole. A critical feature of this effort is that patients will be deeply involved in creating these policies."

The privacy aspect of the database is a work in progress. "As we develop overall governance policies for PCORnet and create the structures, methods, and means that will allow networks to operate together, we'll provide specific information on how research teams can access the data and how queries will be handled, prioritized, and answered," says Selby. "We expect patient data provided in response to research requests will be stripped of personal identifying information, which will not leave the health system or original network, unless patients have explicitly consented to its release for a particular research purpose" (emphasis added).

In conclusion, Selvin stated: "During the 18-month development phase, which ends September 2015, we will work continuously to improve the quality of the data and the efficiency of the PCORnet's capacity to support research." He believes "each individual network will benefit from comparing approaches, and the most successful procedures and policies will be shared and refined." Finally, he predicted "that PCORnet will be a true game-changer in health research."

The Post also noted a number of questions, including: "How will research questions be prioritized? How should disagreements be resolved? Should pharmaceutical companies and insurers be able to access the records and, if so, under what circumstances? What about the Centers for Disease Control and Prevention? The information could help epidemiologists track outbreaks and clusters of disease in a way they have never done before."

Also, "critically important to the multibillion-dollar pharmaceutical industry, how will the Food and Drug Administration view this type of research when considering applications for new drugs or in recalling old ones?"

June 19, 2013

PCORI Funding Announcement – Clinical Data and Patient Powered Research Networks

In late April of this year, the Patient-Centered Outcomes Research Institute (PCORI) announced two new funding opportunities totaling $68 million to conduct patient-centered comparative clinical effectiveness research (CER) via the development of a National Patient-Centered Clinical Research Network (NPCCRN). 

One of the bigger pieces of the Patient Protection and Affordable Care Act (PPACA) was the idea to lower healthcare costs through CER.  To achieve this goal, PPACA (Section 6301 and Section 10602, Public Law 111-148), created the Patient-Centered Outcomes Research Institute (PCORI), an independent, non-profit health research organization.  PCORI will have an estimated $3 billion over the next decade to fund CER.  

PCORI was created to conduct research to provide information about the best available evidence to help patients and their health care providers make more informed decisions.  PCORI's research is intended to give patients a better understanding of the prevention, treatment and care options available, and the science that supports those options.  Below is a short summary of some of the revisions made by the PCORI Board.

The announcements fall under one of PCORI's five National Priorities for Research, "Accelerating Patient-Centered and Methodological Research," and aim to improve the nation's capacity to efficiently conduct CER.

The NPCCRN will serve as a large, highly representative, national patient centered clinical research network for conducting clinical outcomes research.  As stated in the notice, the program will promote a more comprehensive, complete, longitudinal data infrastructure; broader participation of patients, clinicians, health systems, and payers in the research process; and improvements in analytic methods for both observational  and experimental CER.

A major component of this network are Clinical Data Research Networks (CDRNs), or system based networks (such as hospital systems) that have the potential to become an ideal electronic network, without structural impediments, and Patient Powered Research Networks (PPRNs), which are groups of patients interested in forming a research network and in participating in research. 

PCORI will fund up to $56 million to support up to eight new or existing CDRNs that will develop the capacity to conduct randomized comparative effectiveness studies using data from clinical practice in large, defined populations. PCORI also will fund up to $12 million to support up to 18 new or existing PPRNs and their progression toward a reusable, scalable, and sustainable research network.

Required letters of intent (LOI) from applicants are due June 19 and complete applications are due September 27. PCORi's Online System opened on May 15th and PCORi will be hosting a Pre-LOI Informational Webinar on Thursday, June 6, 2013 at 3:00PM (EST). Awards will be announced in December 2013.

 "We see this initiative, unlike many past efforts, as an opportunity to bring together the many sectors within healthcare that can be both sources and users of the types of rich clinical data that, if carefully and appropriately gathered and used, can significantly advance patient-centered CER," said PCORI Executive Director Joe Selby, MD, MPH


Clinical Data Research Networks (CDRNs)

Through this funding announcement, PCORI seeks to support new or existing CDRNs that will develop the capacity to conduct randomized comparative effectiveness studies using data from clinical practice in a large, defined population (at least one million people by the end of Phase One for conditions other than rare diseases). PCORI has defined the characteristics of an ideal CDRN to include the following:

  1. Coverage of large, diverse, defined populations unselected for a particular disease, condition, or procedure; ability to capture complete clinical information on this population over time, including longitudinal information on clinical care, changes in clinical characteristics and conditions, and the occurrence of clinical care or outcomes, within or outside the system.


  1. Involvement of multiple (two or more) health systems, with data interoperability and data standardization to allow efficient, valid sharing of individual or aggregate data across systems for purposes of data analysis.
  1. The ability to efficiently contact patients for the purposes of efficient recruitment; collecting patient-reported information; and maintaining consistently high levels of participation in research studies, including sustained randomization, participation, and follow-up over time.
  1. Demonstrated ability to engage substantial patient populations with selected conditions, both within and outside their systems, for purposes of generating research questions, participating in network governance, or in appropriate research studies.
  1. Involvement of the healthcare system leadership in governance and use of the network to enhance network efficiency, utility, and sustainability.
  1. Willingness to serve as a national data infrastructure resource for the conduct of CER by researchers outside the network.
  1. Capacity to support large-scale comparative effectiveness trials, as well as observational studies of multiple research questions, including prevention and treatment, at low marginal cost, with substantive patient involvement throughout, including formulation of research questions and essential study characteristics, study participation, and dissemination of study findings.
  1. Capacity to embed research activity within functioning healthcare systems without disrupting the business of providing health care; alignment of human subjects oversight, IRB review and approval, and informed consent procedures with the level of risk in proposed comparative effectiveness studies, including plans to obtain buy-in from all organizations to accept review of specific projects under auspices of a central IRB.
  1. Clear, proven policies to maintain data security, patient privacy, and confidentiality; ability to collect, store, retrieve, process, or ship biological specimens for research purposes, with appropriate consent, for use by qualified researchers.
  1. Ability to streamline subcontracting processes for research involving multiple sites.

Patient Powered Research Networks (PPRNs)

Through this funding announcement, PCORI seeks to support new or existing PPRN's that are comprised of patients and/or caregivers who are motivated to build an ideal network and play an active role in patient-centered comparative effectiveness research (CER). PCORI has defined the characteristics of an ideal PPRN as comprised of a patient community or group that:

  • Is comprised of patients linked by a common condition, may also include interested caregivers or clinicians, and is enthusiastic about participating in patient-centered outcomes research, including the potential to contribute research ideas, share data, adhere to protocols, and participate in observational studies and randomized clinical trials;
  • Is interested in and willing to increase the quantity and quality of information collected from patients that is suitable for research from an activated patient community of at least 50,000 patients (less for patients with rare disorders);
  • Has a governance structure and operating policies that ensure patient control, that can establish relationships with qualified researchers and that can generate research questions from the community's membership and accumulate relevant clinical and patient-reported outcomes data from a high proportion (at least 80%) of the membership;
  • Has strategies to enhance and report the diversity and the representativeness of the patient community as it expands;
  • Is interested in being actively involved in planning and conducting dissemination of research findings to patients and providers;
  • Is willing to explore novel and efficient approaches for patient members to contribute their electronic clinical data to the PPRN. For example, patients could share their own data directly (obtained by providers and hospitals through the View, Download, Transmit (VDT) requirements on Meaningful Use or the Blue Button functions offered by health plans and other data holders) or ask the health care delivery sites they use to provide the data;
  • Is willing to explore novel and efficient approaches for patient members to collect self-reported data, including use of remote monitoring devices, mobile apps, and self-reported observations of daily living;
  • Is willing to participate in a program-wide Steering Committee that aims to share insights and approaches across the funded projects, with the aim of converging on a standards-based, inter-operable approach to building patient-powered networks and, in a subsequent funding cycle, merging them with clinical research data networks

February 14, 2013

PCORI News Plus FDA Suggestions on Comparative Effectiveness Research

FDA Headquarters

The Board of Governors of the Patient-Centered Outcomes Research Institute (PCORI) at its 19 November 2012 meeting in Boston, MA adopted 47 revised methodology standards that are intended to guide the comparative effectiveness research (CER) funded by PCORI, reported RAPS.  The Board also authorized at the meeting the development of three new CER funding announcements:  

  • Treatment options for uterine fibroids,
  • the safety and benefits of treatment options for severe asthma, and 
  •  fall prevention in the elderly.   

One of the bigger pieces of the Patient Protection and Affordable Care Act (PPACA) was the idea to lower healthcare costs through comparative effectiveness research (CER).  To achieve this goal, PPACA (Section 6301 and Section 10602, Public Law 111-148), created the Patient-Centered Outcomes Research Institute (PCORI), an independent, non-profit health research organization.  PCORI will have an estimated $3 billion over the next decade to fund CER.  

PCORI was created to conduct research to provide information about the best available evidence to help patients and their health care providers make more informed decisions.  PCORI’s research is intended to give patients a better understanding of the prevention, treatment and care options available, and the science that supports those options.  Below is a short summary of some of the revisions made by the PCORI Board.

FDA and Comparative Effectiveness 

In addition to the new measures, an interesting post by Robert Temple MD, Deputy Center Director for Clinical Science at FDA’s Center for Drug Evaluation and Research (CDER) noted that “comparative effectiveness approaches [are] not always the most effective.”  Temple explained that while it is not surprising to want to compare data, “the main difficulty with doing comparative studies is that the effects of most drugs, while valuable, are not very large, so that even showing a difference between the drug and no treatment (a placebo treatment) is not easy.”  

Moreover, Temple noted that “Showing a difference between two effective drugs, a difference much smaller than the difference between a drug and no treatment, is very challenging and will usually need a very large study.”  While comparative data do exist that show advantages for some members of a class over others, “they are not common,” he noted.   

He noted that within a class of drugs like antidepressants or antipsychotics, there are relatively few cases where we have been able to say that one drug is better than another, however, there are a few.  For example, “the antipsychotic drug clozapine, is generally thought to be more effective than other drugs in its class, however, it has a toxicity that no other members of the class have. Clozapine causes a marked decrease in the number of certain white blood cells. But it was shown to work in people who did not respond to other drugs.  This showing was critical to its approval.”

“Some drugs that inhibit platelets in patients with coronary artery disease have been studied in trials that compared the new drugs with an older drug. In some cases, the newer drugs had better effects, reducing the rate of heart attacks, though sometimes causing more bleeding.”  Temple also explained that “It is fairly common for a new cancer drug to be more effective than an older therapy.” 

“There is a popular class of anti-hypertensive drugs called angiotensin receptor blockers. With considerable effort, and quite large studies, two companies have shown that their drug had a larger effect on blood pressure than other members of the class.”

Temple went on to explain that there is “some hope that instead of doing large, randomized trials to show differences, between treatments, observational studies, i.e., epidemiologic data, can be used to do this.”  There is considerable disagreement on whether this is possible, he explained.   

His “belief is that any differences between effective drugs are likely to be very small and can be credibly detected only in randomized trials.  Whether pooling the results of multiple controlled trials (meta-analyses) will work is an area for discussion, but to do this you need many trials with the same comparison, a rare occurrence.” 

Instead, Temple suggested using “people who have not responded to one drug, and then randomize them back to the drug that didn't work and to another drug.  This is particularly interesting when the two drugs are in the same pharmacologic class.”  He noted that there are individualized responses to treatments where some people do better on one drug than another very similar drug.  Thus, “If it is really true that people who don't respond to one member of a drug class actually respond to another member of the class, we can design the perfect study to test this.” 

“For example, you could take people who don't respond to a migraine drug and randomize them back to a new migraine drug, the old migraine drug the one they didn’t respond to, and a placebo.  If it's true that there are individual differences that are important, then the new drug ought to be able to show its advantage over the drug that didn’t work.”  Temple noted a few studies that have tried to do this, including Clozapine; the first angiotensin-converting-enzyme inhibitor, captopril; and Merck’s Celebrex.   

Finally, Temple noted that an interesting and therapeutically important question to also consider is whether, “if a drug causes a side effect another member of the drug class, or a drug of a different class can be substituted and not cause the side effect.”  He noted one experiment in which women who received anti-depressants had poor sexual functions, but when they were switched and randomized, the new drug did not cause the sexual dysfunction.   

Standards Associated with Patient-Centeredness 

Originally, this standard only included individuals who have the condition or who are at risk of the condition.  The revisions now include “other relevant stakeholders,” which may include “clinicians, administrators, policy makers, or others involved in health care decision making.” 

For use of patient reported outcomes when patients are the best source of information, the Board added that “Caregiver reports may be appropriate if the patient cannot self-report the outcomes of interest. If patient-reported outcome (PRO) measures are not planned for use in the study, justification must be provided.  The Board also changed dissemination measure, now requiring researchers to “Support dissemination and implementation of study results by suggesting strategies, indicating clinical and policy implications, and working with patients or organizations to report results in a manner understandable to each target audience.” 

Standards for Systematic Reviews 

Systematic reviews are used to answer questions based on comprehensive consideration of all the pertinent evidence, and can also identify the gaps in evidence and how they might be resolved. Standards for systematic reviews are currently in use, but credible authorities such as Cochrane and AHRQ, vary somewhat in their recommended standards.  The Institute of Medicine recently issued standards that draw broadly from available sources.  However not all standards are based on empiric evidence and reliable systematic reviews may use alternative approaches.  The Board added that, “The methodology committee endorses these standards but recognize that there can be flexibility in the application of some of standards without compromising the validity of the review. 

General and Crosscutting Methods For All PCORI  

The Board added a completely new requirement, Describe Data Linkage Plans, if Applicable.  For studies involving linkage of patient data from two or more sources (including registries, data networks and others), describe (1) each data source and its appropriateness, value and limitations for addressing specific research aims, and (2) any additional requirements that may influence successful linkage, such as information needed to match patients, selection of data elements, and definitions used, and (3) the procedures and algorithm(s) employed in matching patients, including the success, limitations and any validation of the matching algorithm  

Causal Inference Standards  

Define Analysis Population Using Covariate Histories Information Available at Study Entry :  Decisions about whether patients are included in an analysis should be based on information available at each patient’s time of study entry “in prospective studies or on information from a defined time period” prior to “the exposure in retrospective studies. For time-varying treatment or exposure regimes, specific time points should be clearly specified and the covariates history up to and not beyond those time points should be used as population descriptors.” 

Measure Confounders before Start of Exposure. Report data on confounders with study results.  In general, variables for use in confounding adjustment (either in the design or analysis) should be ascertained and measured prior to the first exposure to the therapy (or therapies) under study.  “If confounders are time varying, specific time points for the analysis of the exposure effect should be clearly specified and the confounder history up to and not beyond those time points should be used in that analysis.”   

Standards for Heterogeneity of Treatment Effect (HTE)  

State the Goals of HTE Analyses: State the inferential goal of each HTE analysis specifying how it is related to the topic of the research, translate this into an analytic approach and highlight the linkages between the two.  Identify each analysis as either hypothesis driven (sometimes denoted confirmatory) or hypothesis generating (sometime denoted exploratory).  

For all HTE Analyses, Pre-specify the analysis plan; for Hypothesis driven HTE Analyses, Pre-specify Hypotheses for Each Subgroup Effect.  The study protocol should unambiguously pre-specify planned HTE analyses.  Pre-specification of hypothesis driven HTE analyses should include a clear statement of the hypotheses the study will evaluate, including how groups will be defined (e.g. by multivariate score or stratification) and outcome measures, and the direction of the expected treatment effects. The prespecfied hypotheses should be based on prior evidence which should be described clearly in the study protocol and published paper.  

All HTE claims must be based on appropriate statistical contrasts among groups being compared, such as interaction tests or estimates of differences in treatment effect. A common error in HTE analyses is to claim differences in treatment effect when one group shows a statistically significant treatment effect and another does not. To claim differences in treatment effect among subgroups, appropriate statistical methods must be used to directly contrast them. Such contrasts include, but are not limited to interaction tests, differences in treatment effect estimates with standard errors, or a variety of approaches to adjusting the estimated subgroup effect, such as Bayesian shrinkage estimates. Within each subgroup level, studies should present the treatment effect estimates and measures of variability



Preview | Powered by FeedBlitz


April 2018
Sun Mon Tue Wed Thu Fri Sat
1 2 3 4 5 6 7
8 9 10 11 12 13 14
15 16 17 18 19 20 21
22 23 24 25 26 27 28
29 30