Primary Hip Replacement Prostheses and Their Evidence Base
Primary Hip Replacement Prostheses and Their Evidence Base
This systematic review of the literature shows that 8% of all primary hip replacement prostheses implanted in 2011 and recorded by the National Joint Registry (NJR) had no readily available evidence relating to their safety or effectiveness. This is likely to be an underestimation of the true problem, as much of the evidence that does exist for the other unrated prostheses is of low quality or relates to short term outcomes only. This is of great concern, particularly in light of the widespread publicity surrounding recent safety problems with regard to some resurfacing and other large diameter metal-on-metal joint replacements.
The ODEP system of grading primary hip components offers clinicians a simplified, device specific rating for clear comparison of devices' performance on relevant clinical criteria. It is troubling to note that 45% of the brands available for primary hip replacement have no ODEP rating, meaning, according to the ODEP guidelines, that they should be implanted only as part of a trial. What is more heartening is that despite the large number of unrated brands available, the most widely used prostheses are highly rated by the ODEP system, implying that most orthopaedic surgeons use prostheses that are supported by a good evidence base.
Why some surgeons would choose to use prostheses with no available evidence to support their use outside of a research study is not clear. Possible reasons include the introduction of new prostheses by manufacturers who have well established and trusted implants available. These new products are then judged, perhaps erroneously, to be of the same high standard in terms of longevity and clinical outcome. Another situation may arise whereby a well established prosthesis is "improved" by way of a minor modification. Unfortunately, numerous examples exist of minor design changes having disastrous effects on implants' longevity.
Murray, Carr, and Bulstrode reviewed the evidence for total hip replacement in 1995. They found that only 30% of hip replacements available had any evidence supporting their use. At the time, they advocated the need for greatly improved collection of evidence and proposed improvements in the regulation of implants and devices. Despite the recommendations of this and other groups, the evidence base in relation to hip replacements has improved only marginally over the past 18 years. The reasons for this are unclear. It may be related to the rapid expansion in the number of devices introduced onto the market during the past two decades as demand for hip arthroplasty increases worldwide. In 1996 there were 62 primary hip replacement components on the market in the UK; in 2011 there were 261. In addition, the quality of studies in the orthopaedic literature is of a generally low standard. Our study has identified only six randomised control trials in the literature, compared with the 265 implants currently available. Most of the studies identified were case series. Properly conducted randomised controlled trials are more difficult to run with orthopaedic implants than with drugs or other interventions, and this may also have contributed to the paucity of good quality evidence in this sphere.
Although the ODEP already provides implant ratings based on levels of evidence, manufacturers are not required to submit published negative evidence in the case of either pre-entry or unclassified prostheses. Therefore, a device could sit in either category despite several negative peer reviewed publications. This systematic review has shown that 64% of unclassified prostheses have published peer reviewed evidence that may not have been submitted to the ODEP.
The regulation process also seems to be entirely inadequate. The award of a Conformité Européenne mark is conditional on a device meeting a series of laboratory based standards that may not equate to the safety or effectiveness of an implant in patients. A Conformité Européenne mark may also be awarded in cases of "existing similarity," where the new device closely resembles an existing design. However, as discussed above, small changes in design have been shown to have major deleterious effects on an implant’s clinical effectiveness or lifespan.
The NJR is effective in auditing current practice but was designed to monitor the success of implants in relation to when and how often they need to be replaced or revised. Thus, although patient reported outcome measures are due to be introduced as part of the annual report, in its current form the NJR's report does not recognise problems with implants until they are revised and so may not be the best tool for evaluating new prostheses. Most implants are typically introduced in small numbers initially, which makes outliers difficult or impossible to detect. This is shown by the recent problems with some metal-on-metal joint replacements, which were identified in single centre cohort studies more than three years before the NJR identified them as outliers, Arguably, well designed controlled studies would have identified the problem even more quickly with fewer patients experiencing the adverse consequences of a substandard design. In addition, the NJR lists only implants that are in open use and for which reports are submitted. Consequently, devices that are available to some surgeons but have not yet been made available on the open market do not appear in the NJR's report. These factors can lead to a delay in the identification of failing implants. The National Institute for Health and Care Excellence (NICE) suggests that the use of more refined outcome measures such as radiostereometric analysis, which aims to identify early loosening of implants by using bi-planar radiographs, may help to detect early problems.
The phased introduction of devices, combined with the use of surrogate outcome measures, has been called for to provide early identification of poorly performing implants. This correlates with the IDEAL framework ensuring that the introduction of new devices is controlled and regulated in phases. The future of medical device regulation needs to be a careful balance between the requirement to facilitate innovation and the imperative to safeguard patients. Following the example of pharmaceutical regulation by implementing a phased introduction of new orthopaedic implants would seem prudent. It has been proposed that innovative technologies should be made available in a few specialist units, where the evidence can be objectively gathered and any problems with implants' resilience identified quickly using surrogate outcome measures.
The counter argument debates the damage over-regulation can do to innovation and development in the field of medicine. The cost of medical implants and devices may also rise if they are required to undergo lengthy pre-clinical and clinical testing. However, significant cost savings may accrue if the number of devices on the market were limited to only those devices with a solid evidence base for their use. Tackling this question requires a delicate balance.
Many of the concerns in this process relate to the evidence required to market an implant or device. Public availability of a list of current medical implants and devices, including pre-marketing data and peer reviewed publications, is needed. This may improve transparency in the early stages of implant introduction, allowing surgeons and patients to make more informed decisions.
A major limitation to our study relates to the requirement that a prosthesis be specifically named in a publication to meet our inclusion criteria. Relevant published evidence may therefore not have been identified, for instance, if a specific implant was simply referred to as "an uncemented acetabular cup" or as a "proximal loading femoral stem." However, we felt that the explicit naming of a prosthesis is necessary if surgeons or commissioners are to locate evidence that can inform their decision making as to the use of a particular prosthesis. Nevertheless, evidence for some implants may have been missed if the device had undergone a change of brand name since evidence was published. However, in all cases in which no evidence could be found, we contacted the manufacturers directly to request supportive data for the use of their implant, which gave the opportunity for missed evidence to be brought to our attention.
Another limitation is that the evidence for some early phase implants will not have been detected if they are part of ongoing prospective cohort studies or randomised controlled trials that have yet to report. We have included, where identified, “pre-entry” devices in our analysis, and these prostheses are likely to be undergoing prospective studies and so would not yet have published evidence available in the literature. However, the number of prostheses implanted as part of prospective and unreported clinical studies is likely to represent only a small proportion of the 10,617 devices implanted with no available evidence.
The evidence presented in this study relates to prostheses implanted in the UK. However, we believe the results of this study can be applied to other healthcare settings, given that most of the prostheses in our systematic review are available in most other developed countries, in Europe, Australasia, and the United States.
NICE has set a clear benchmark of an ODEP rating of 10C as the minimum clinical standard it recommends for general implantation. Our review has determined that only 49% (118/261) of prostheses implanted overall achieved a 10A/B/C rating and that almost one in four prosthesis brands available to surgeons have no evidence to support their use. Although these brands are used relatively infrequently, at least 7% of all prostheses implanted lack evidence of clinical effectiveness or longevity. This study shows that the need still exists for an improved and more rigorous approach to regulation of devices to avoid devices with no available evidence being used in a widespread and uncontrolled manner.
Discussion
This systematic review of the literature shows that 8% of all primary hip replacement prostheses implanted in 2011 and recorded by the National Joint Registry (NJR) had no readily available evidence relating to their safety or effectiveness. This is likely to be an underestimation of the true problem, as much of the evidence that does exist for the other unrated prostheses is of low quality or relates to short term outcomes only. This is of great concern, particularly in light of the widespread publicity surrounding recent safety problems with regard to some resurfacing and other large diameter metal-on-metal joint replacements.
Evidence Ratings
The ODEP system of grading primary hip components offers clinicians a simplified, device specific rating for clear comparison of devices' performance on relevant clinical criteria. It is troubling to note that 45% of the brands available for primary hip replacement have no ODEP rating, meaning, according to the ODEP guidelines, that they should be implanted only as part of a trial. What is more heartening is that despite the large number of unrated brands available, the most widely used prostheses are highly rated by the ODEP system, implying that most orthopaedic surgeons use prostheses that are supported by a good evidence base.
Why some surgeons would choose to use prostheses with no available evidence to support their use outside of a research study is not clear. Possible reasons include the introduction of new prostheses by manufacturers who have well established and trusted implants available. These new products are then judged, perhaps erroneously, to be of the same high standard in terms of longevity and clinical outcome. Another situation may arise whereby a well established prosthesis is "improved" by way of a minor modification. Unfortunately, numerous examples exist of minor design changes having disastrous effects on implants' longevity.
Murray, Carr, and Bulstrode reviewed the evidence for total hip replacement in 1995. They found that only 30% of hip replacements available had any evidence supporting their use. At the time, they advocated the need for greatly improved collection of evidence and proposed improvements in the regulation of implants and devices. Despite the recommendations of this and other groups, the evidence base in relation to hip replacements has improved only marginally over the past 18 years. The reasons for this are unclear. It may be related to the rapid expansion in the number of devices introduced onto the market during the past two decades as demand for hip arthroplasty increases worldwide. In 1996 there were 62 primary hip replacement components on the market in the UK; in 2011 there were 261. In addition, the quality of studies in the orthopaedic literature is of a generally low standard. Our study has identified only six randomised control trials in the literature, compared with the 265 implants currently available. Most of the studies identified were case series. Properly conducted randomised controlled trials are more difficult to run with orthopaedic implants than with drugs or other interventions, and this may also have contributed to the paucity of good quality evidence in this sphere.
Although the ODEP already provides implant ratings based on levels of evidence, manufacturers are not required to submit published negative evidence in the case of either pre-entry or unclassified prostheses. Therefore, a device could sit in either category despite several negative peer reviewed publications. This systematic review has shown that 64% of unclassified prostheses have published peer reviewed evidence that may not have been submitted to the ODEP.
Regulatory Process
The regulation process also seems to be entirely inadequate. The award of a Conformité Européenne mark is conditional on a device meeting a series of laboratory based standards that may not equate to the safety or effectiveness of an implant in patients. A Conformité Européenne mark may also be awarded in cases of "existing similarity," where the new device closely resembles an existing design. However, as discussed above, small changes in design have been shown to have major deleterious effects on an implant’s clinical effectiveness or lifespan.
The NJR is effective in auditing current practice but was designed to monitor the success of implants in relation to when and how often they need to be replaced or revised. Thus, although patient reported outcome measures are due to be introduced as part of the annual report, in its current form the NJR's report does not recognise problems with implants until they are revised and so may not be the best tool for evaluating new prostheses. Most implants are typically introduced in small numbers initially, which makes outliers difficult or impossible to detect. This is shown by the recent problems with some metal-on-metal joint replacements, which were identified in single centre cohort studies more than three years before the NJR identified them as outliers, Arguably, well designed controlled studies would have identified the problem even more quickly with fewer patients experiencing the adverse consequences of a substandard design. In addition, the NJR lists only implants that are in open use and for which reports are submitted. Consequently, devices that are available to some surgeons but have not yet been made available on the open market do not appear in the NJR's report. These factors can lead to a delay in the identification of failing implants. The National Institute for Health and Care Excellence (NICE) suggests that the use of more refined outcome measures such as radiostereometric analysis, which aims to identify early loosening of implants by using bi-planar radiographs, may help to detect early problems.
The phased introduction of devices, combined with the use of surrogate outcome measures, has been called for to provide early identification of poorly performing implants. This correlates with the IDEAL framework ensuring that the introduction of new devices is controlled and regulated in phases. The future of medical device regulation needs to be a careful balance between the requirement to facilitate innovation and the imperative to safeguard patients. Following the example of pharmaceutical regulation by implementing a phased introduction of new orthopaedic implants would seem prudent. It has been proposed that innovative technologies should be made available in a few specialist units, where the evidence can be objectively gathered and any problems with implants' resilience identified quickly using surrogate outcome measures.
The counter argument debates the damage over-regulation can do to innovation and development in the field of medicine. The cost of medical implants and devices may also rise if they are required to undergo lengthy pre-clinical and clinical testing. However, significant cost savings may accrue if the number of devices on the market were limited to only those devices with a solid evidence base for their use. Tackling this question requires a delicate balance.
Many of the concerns in this process relate to the evidence required to market an implant or device. Public availability of a list of current medical implants and devices, including pre-marketing data and peer reviewed publications, is needed. This may improve transparency in the early stages of implant introduction, allowing surgeons and patients to make more informed decisions.
Limitations of Study
A major limitation to our study relates to the requirement that a prosthesis be specifically named in a publication to meet our inclusion criteria. Relevant published evidence may therefore not have been identified, for instance, if a specific implant was simply referred to as "an uncemented acetabular cup" or as a "proximal loading femoral stem." However, we felt that the explicit naming of a prosthesis is necessary if surgeons or commissioners are to locate evidence that can inform their decision making as to the use of a particular prosthesis. Nevertheless, evidence for some implants may have been missed if the device had undergone a change of brand name since evidence was published. However, in all cases in which no evidence could be found, we contacted the manufacturers directly to request supportive data for the use of their implant, which gave the opportunity for missed evidence to be brought to our attention.
Another limitation is that the evidence for some early phase implants will not have been detected if they are part of ongoing prospective cohort studies or randomised controlled trials that have yet to report. We have included, where identified, “pre-entry” devices in our analysis, and these prostheses are likely to be undergoing prospective studies and so would not yet have published evidence available in the literature. However, the number of prostheses implanted as part of prospective and unreported clinical studies is likely to represent only a small proportion of the 10,617 devices implanted with no available evidence.
The evidence presented in this study relates to prostheses implanted in the UK. However, we believe the results of this study can be applied to other healthcare settings, given that most of the prostheses in our systematic review are available in most other developed countries, in Europe, Australasia, and the United States.
Conclusion
NICE has set a clear benchmark of an ODEP rating of 10C as the minimum clinical standard it recommends for general implantation. Our review has determined that only 49% (118/261) of prostheses implanted overall achieved a 10A/B/C rating and that almost one in four prosthesis brands available to surgeons have no evidence to support their use. Although these brands are used relatively infrequently, at least 7% of all prostheses implanted lack evidence of clinical effectiveness or longevity. This study shows that the need still exists for an improved and more rigorous approach to regulation of devices to avoid devices with no available evidence being used in a widespread and uncontrolled manner.