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FROM METHODS TO POLICY
Practice-based research networks: will their promise become reality? Robert W Dubois*
Patients often ask their provider “given my personal characteristics and health history, what are my treatment options and what are the potential benefits and risks of those options? And, if I don’t respond to the first therapy what are the next steps in treating my condition?” Unfortunately, the evidence to answer these questions is often unavailable, in part because we look to randomized controlled trials (RCTs) as the ‘gold standard’ for evidence. RCTs are conducted in ‘research grade’ environments with carefully selected patients and carefully selected treatment settings. These characteristics enhance their ability to determine whether a therapy can work (efficacy), but not whether the results can be generalized to routine care or routine patients (effectiveness). An alternative, practice-based research networks (PBRNs) can generate evidence with a more real-world view perspective. PBRNs typically consist of primary care clinicians in routine practice who also conduct studies on the patient populations that they serve. These networks have the patients and infrastructure to conduct pragmatic clinical trials, collect data for prospective registries or house information for retrospective analyses. In contrast to RCTs, pragmatic trials may enroll a broader more typical patient population, have active therapy comparisons (vs placebo in many RCTs), require patients to purchase and obtain their medications as is typical of routine care, may not have predefined follow-up testing or office visits (which resembles more usual patient experience), and may allow the clinician to modify the regimen if the patient’s condition does not improve or side effects occur. In addition to answering questions similar to those posed by the patient above, these pragmatic trial characteristics were viewed by payers in a recent survey as valuable [1]. The importance of PBRNs and pragmatic studies was also recognized by the Agency for Healthcare Research and Quality [2], the NIH [3] and the Patient Centered Outcomes Research Institute. The Patient Centered Outcomes Research has announced US$100 million in funding for the National Patient-Centered Clinical Research Network [4]. As we consider the development and use of PBRNs, it will be critical to carefully examine and shape the research questions to be addressed. It is not only the ability of these PBRNs to raise practical and important research questions, but also their ability to more rapidly and efficiently answer them that holds great promise. The PICOTS framework can help to identify the most pressing, practical and real-world questions that traditional RCTs may not address: ■■ Patients: what types of patients have been studied in RCTs and which ones remain unstudied? Older ones? Those with comorbidities? Those with lesser disease severity? ■■
“…practice-based research networks can generate evidence with a more real-world view perspective.”
*National Pharmaceutical Council, 1717 Pennsylvania Avenue NW Suite 800, Washington DC 20006, USA Tel.: +1 202 827 2079 [email protected]
Interventions: closely monitored RCTs ensure that most patients receive the intervention as envisioned. This compliance (e.g., with often complex interventions or costly medication regimens) or provider expertise (e.g., robotic surgery) probably differs in routine practice. What are the critical intervention characteristics that differ in the real world and how can they be captured in a PBRN study?
10.2217/CER.14.7 © 2014 Future Medicine Ltd
3(2), 123–124 (2014)
part of
ISSN 2042-6305
123
from methods TO POLICY Dubois ■■
Comparators: RCTs often use placebo comparators or only use a single comparator. In many cases, there may be multiple alternatives where comparison data would be helpful;
■■
Outcomes: PBRNs have the opportunity to collect information not typically collected in traditional RCTs, such as medication compliance, total cost of care, quality of life and workplace productivity;
■■
Time: given that PBRN-enrolled patients will continue to receive care beyond the length of a typical RCT, these studies can provide data not only in the short term, but also over longer than typical time periods;
■■
Setting: PBRNs serve to incorporate experiences from smaller provider practices in addition to those in large settings. Are there salient characteristics associated with the location of care that influence patient outcomes?
PBRNs also provide an opportunity to more fully explore heterogeneity of treatment response, where the average response may not apply to an individual patient. Payers both public and private are narrowing medication choice through limited formularies and substantial patient financial burden based upon population level, mean response. Does limiting therapeutic choice harm patients? PBRNs can use cross-over designs or N-of-1 approaches to more definitively indicate which patients respond best to what therapy. PBRNs may also enable more compelling evidence to be efficiently amassed. Only rarely does a single, large, costly, traditional RCT change clinical practice. Physicians and patients often need to observe similar findings from multiple studies. PBRNs may satisfy this need. Despite the promise of PBRN-based research, important issues remain unaddressed: References 1
124
Ratner J, Mulins CD, Buesching DP, Cantrell RA. Pragmatic clinical trials: US payers’ view on their value. Am. J. Manag. Care 19, 3158–3165 (2013).
■■
What is the best way for the US FDA to incorporate PBRN-derived evidence into the approval process for drugs and devices? And how should this evidence be incorporated into the regulations governing manufacturer communications after initial approval?
■■
Under what circumstances should clinical practice guideline groups and payers be willing to incorporate results from PBRN studies?
■■
What are the new considerations clinicians should use (and be taught) regarding how these new forms of evidence can be applied to their patients and settings.
In conclusion, PBRNs present an important addition to the evidence generation armamentarium. To succeed and have a practical and sustainable infrastructure, we need carefully selected and practically relevant research questions, compelling evidence from multiple studies, broad acceptance of PBRNs by the payer and clinical communities, regulatory clarification and clear guidance on communication of evidence from these sources. Without clarity around these issues, the promise of PBRNs and the requested information from our above patient might remain unfulfilled. Financial & competing interests disclosure RW Dubois is employed by the National Pharmaceutical Council, a policy research organization supported by the nation’s major research-based pharmaceutical companies. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
2
AHRQ. Primary Care Practice-Based Research Networks Resource Center. http://pbrn.ahrq.gov
3
Westfall JM, Mold J, Fagnan L. Practicebased research – ‘Blue Highways’ on the NIH roadmap. JAMA 297(4), 403–406 (2007).
J. Comp. Eff. Res. (2014) 3(2)
4
PCORnet: The National Patient-Centered Clinical Research Network. www.pcori.org/funding-opportunities/ pcornet-national-patient-centered-clinicalresearch-network/
future science group
FROM METHODS TO POLICY
Practice-based research networks: will their promise become reality? Robert W Dubois*
Patients often ask their provider “given my personal characteristics and health history, what are my treatment options and what are the potential benefits and risks of those options? And, if I don’t respond to the first therapy what are the next steps in treating my condition?” Unfortunately, the evidence to answer these questions is often unavailable, in part because we look to randomized controlled trials (RCTs) as the ‘gold standard’ for evidence. RCTs are conducted in ‘research grade’ environments with carefully selected patients and carefully selected treatment settings. These characteristics enhance their ability to determine whether a therapy can work (efficacy), but not whether the results can be generalized to routine care or routine patients (effectiveness). An alternative, practice-based research networks (PBRNs) can generate evidence with a more real-world view perspective. PBRNs typically consist of primary care clinicians in routine practice who also conduct studies on the patient populations that they serve. These networks have the patients and infrastructure to conduct pragmatic clinical trials, collect data for prospective registries or house information for retrospective analyses. In contrast to RCTs, pragmatic trials may enroll a broader more typical patient population, have active therapy comparisons (vs placebo in many RCTs), require patients to purchase and obtain their medications as is typical of routine care, may not have predefined follow-up testing or office visits (which resembles more usual patient experience), and may allow the clinician to modify the regimen if the patient’s condition does not improve or side effects occur. In addition to answering questions similar to those posed by the patient above, these pragmatic trial characteristics were viewed by payers in a recent survey as valuable [1]. The importance of PBRNs and pragmatic studies was also recognized by the Agency for Healthcare Research and Quality [2], the NIH [3] and the Patient Centered Outcomes Research Institute. The Patient Centered Outcomes Research has announced US$100 million in funding for the National Patient-Centered Clinical Research Network [4]. As we consider the development and use of PBRNs, it will be critical to carefully examine and shape the research questions to be addressed. It is not only the ability of these PBRNs to raise practical and important research questions, but also their ability to more rapidly and efficiently answer them that holds great promise. The PICOTS framework can help to identify the most pressing, practical and real-world questions that traditional RCTs may not address: ■■ Patients: what types of patients have been studied in RCTs and which ones remain unstudied? Older ones? Those with comorbidities? Those with lesser disease severity? ■■
“…practice-based research networks can generate evidence with a more real-world view perspective.”
*National Pharmaceutical Council, 1717 Pennsylvania Avenue NW Suite 800, Washington DC 20006, USA Tel.: +1 202 827 2079 [email protected]
Interventions: closely monitored RCTs ensure that most patients receive the intervention as envisioned. This compliance (e.g., with often complex interventions or costly medication regimens) or provider expertise (e.g., robotic surgery) probably differs in routine practice. What are the critical intervention characteristics that differ in the real world and how can they be captured in a PBRN study?
10.2217/CER.14.7 © 2014 Future Medicine Ltd
3(2), 123–124 (2014)
part of
ISSN 2042-6305
123
from methods TO POLICY Dubois ■■
Comparators: RCTs often use placebo comparators or only use a single comparator. In many cases, there may be multiple alternatives where comparison data would be helpful;
■■
Outcomes: PBRNs have the opportunity to collect information not typically collected in traditional RCTs, such as medication compliance, total cost of care, quality of life and workplace productivity;
■■
Time: given that PBRN-enrolled patients will continue to receive care beyond the length of a typical RCT, these studies can provide data not only in the short term, but also over longer than typical time periods;
■■
Setting: PBRNs serve to incorporate experiences from smaller provider practices in addition to those in large settings. Are there salient characteristics associated with the location of care that influence patient outcomes?
PBRNs also provide an opportunity to more fully explore heterogeneity of treatment response, where the average response may not apply to an individual patient. Payers both public and private are narrowing medication choice through limited formularies and substantial patient financial burden based upon population level, mean response. Does limiting therapeutic choice harm patients? PBRNs can use cross-over designs or N-of-1 approaches to more definitively indicate which patients respond best to what therapy. PBRNs may also enable more compelling evidence to be efficiently amassed. Only rarely does a single, large, costly, traditional RCT change clinical practice. Physicians and patients often need to observe similar findings from multiple studies. PBRNs may satisfy this need. Despite the promise of PBRN-based research, important issues remain unaddressed: References 1
124
Ratner J, Mulins CD, Buesching DP, Cantrell RA. Pragmatic clinical trials: US payers’ view on their value. Am. J. Manag. Care 19, 3158–3165 (2013).
■■
What is the best way for the US FDA to incorporate PBRN-derived evidence into the approval process for drugs and devices? And how should this evidence be incorporated into the regulations governing manufacturer communications after initial approval?
■■
Under what circumstances should clinical practice guideline groups and payers be willing to incorporate results from PBRN studies?
■■
What are the new considerations clinicians should use (and be taught) regarding how these new forms of evidence can be applied to their patients and settings.
In conclusion, PBRNs present an important addition to the evidence generation armamentarium. To succeed and have a practical and sustainable infrastructure, we need carefully selected and practically relevant research questions, compelling evidence from multiple studies, broad acceptance of PBRNs by the payer and clinical communities, regulatory clarification and clear guidance on communication of evidence from these sources. Without clarity around these issues, the promise of PBRNs and the requested information from our above patient might remain unfulfilled. Financial & competing interests disclosure RW Dubois is employed by the National Pharmaceutical Council, a policy research organization supported by the nation’s major research-based pharmaceutical companies. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
2
AHRQ. Primary Care Practice-Based Research Networks Resource Center. http://pbrn.ahrq.gov
3
Westfall JM, Mold J, Fagnan L. Practicebased research – ‘Blue Highways’ on the NIH roadmap. JAMA 297(4), 403–406 (2007).
J. Comp. Eff. Res. (2014) 3(2)
4
PCORnet: The National Patient-Centered Clinical Research Network. www.pcori.org/funding-opportunities/ pcornet-national-patient-centered-clinicalresearch-network/
future science group
