Barg A, Knupp M, Hintermann B. Simultaneous bilateral versus unilateral total ankle replacement: a patient-based comparison of pain relief, quality of life and functional outcome. J Bone Joint Surg Br. 2010 Dec; 92(12): 1659-63. (PubMed ID: 21119171)

WHY did the authors undertake this study?
Patients with lower extremity orthopedic pathology often complain of bilateral and symmetrical involvement. When surgery is indicated in these situations, a staging of procedures is often performed as opposed to bilateral simultaneous intervention. The authors of this study aimed to determine whether bilateral simultaneous total ankle replacement (TAR) was a reasonable option compared to unilateral intervention.

HOW did they attempt to answer this question?
The primary outcome measures of the study were visual analog scale (VAS) scores, AOFAS hind foot scores, and SF-36 scores measured pre-operatively and a 4-month, 1-year and 2-year follow-up.

Inclusion criteria of the experimental population cohort were consecutive patients undergoing bilateral simultaneous TAR. 46 ankles in 23 patients were identified for inclusion over a 7-year data collection period. These were compared to 46 patients undergoing unilateral TAR during the same time frame. No differences were identified between the two study populations.

WHAT were the specific results?
Statistically significant differences were found with respect to VAS scores with the bilateral group having more pain at 4-month follow-up (2.2 vs. 1.6; p=0.004), but there was no difference found at 1-year and 2-year follow-up. Other statistically significant differences were observed within components of the AOFAS and SF-36 scales at 4-month follow-up that disappeared at 1-year and 2-year follow-up.

HOW did the authors interpret these results?
From these results, the authors concluded bilateral simultaneous TAR is a viable option for some patients, but that an initially longer recovery period may be required.

Mocellin S, Pasquali S, Nitti D. The impact of surgery on survival of patients with cutaneous melanoma: revisiting the role of primary tumor excision margins. Ann Surg. 2011 Dec; 253(2): 238-243.

To use our example above, the Barg et al article would have been more in the mold of CER if they had incorporated cost into their outcome measures in addition to the VAS, SF-36 scores and AOFAS scores. They demonstrated that both interventions were similarly effective in terms of long term patient outcome, but what was the difference in terms of hospital expenditure, physical therapy costs, and physician time for examples
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I can indirectly "prove" that randomized controlled trials are generally inefficient and expensive by asking a simple question: how many double-blind, placebo-controlled, multi-center randomized controlled trials have there ever been within the field of foot and ankle surgery? If this is the best evidence that we have, then why don't they fill our journals? For most investigators within our field, it's simply not worth the time and expense for the typical clinical questions that we ask. Supporters of CERs argue that they offer the chance to produce high-powered evidence faster, cheaper and more efficiently.

WHY did the authors undertake this study?
Cutaneous melanoma represents the deadliest form of skin cancer and is one of the malignancies most refractory to medical therapy. Surgical excision remains the mainstay of treatment, but recently some investigators have questioned whether wide (3-5cm) excision offered any additional benefit when compared to narrow (1-2cm) excision of the lesions.

HOW did they attempt to answer this question?
A meta-analysis was performed specifically examining survival analyses following wide and narrow excision of cutaneous melanoma.

WHAT were the specific results?
The results could best be described as borderline. Statistically significant hazard ratios were found with respect to disease recurrence (1.30; p = 0.01) and death by disease (1.28; p = 0.01).

HOW did the authors interpret these results?
From these results the authors concluded that although no definitive conclusions could be drawn, the current evidence supports wide excision compared to narrow excision.

Let's take a closer look at the topic of comparative effectiveness research (CER), particularly as it applies to the Barg, Knupp and Hintermann bilateral simultaneous total ankle replacement (TAR) study. One of the most telling results from this interesting investigation can't be found in any of the tables of the manuscript, nor in the abstract, or in my brief review above. It was that patients with bilateral simultaneous TAR had significantly longer hospital stays than those with unilateral TAR (7.1 days versus 4.9 days; p<0.001). Patients with a unilateral TAR stayed in the hospital for an average of 5 days post-operatively! Now may be a good time to point out that this study was performed in Switzerland, and not at your local hospital.

From an evidence-based medicine standpoint, we hold double-blind, placebo-controlled, multi-center, randomized controlled trials to have the "highest" or "most important" level of evidence. These studies typically have some form of patient function as the primary end-point, although there are literally thousands of potential outcome measures that could be considered. I wanted to use this space to make the audience aware of another stream of thought with respect to medical research, that of comparative effectiveness research. I am not intending to editorialize or pro/con the issue (because it does get quite political); just make you aware of a topic that has been gathering some momentum within the medical field. In fact, two recent pieces of legislation (The American Recovery and Reinvestment Act of 2009 and the Health Care and Education Reconciliation Act of 2010) have really made it a point of emphasis within our own recent health care reform.

Proponents of CER contend that randomized controlled trials are simply too inefficient and too expensive in that they are typically only evaluating one intervention. Think about the very basics of the design. Randomized controlled trials essentially make the assumption that before we can compare a given intervention to another intervention, we must first demonstrate that the intervention is effective compared to a placebo. CERs, on the other hand, differ in that they directly compare at least two (and often more) interventions using clinical trials, computer models and systemic meta-analyses. CERs assume that multiple interventions have some degree of effectiveness, and that our goal should be to compare them to each other, and not to a placebo.

Another important contrast is that CERs also emphasize cost of therapy as a primary outcome measure in addition to intervention efficacy and other patient functional outcomes. It is not implying that the cheapest intervention is the best intervention, simply that if there are two interventions with similar effectiveness, then the cheapest one is the therapy of choice.

To use our example above, the Barg et al article would have been more in the mold of CER if they had incorporated cost into their outcome measures in addition to the VAS, SF-36 scores and AOFAS scores. They demonstrated that both interventions were similarly effective in terms of long term patient outcome, but what was the difference in terms of hospital expenditure, physical therapy costs, and physician time for examples.

I can indirectly "prove" that randomized controlled trials are generally inefficient and expensive by asking a simple question: how many double-blind, placebo-controlled, multi-center randomized controlled trials have there ever been within the field of foot and ankle surgery? If this is the best evidence that we have, then why don't they fill our journals? For most investigators within our field, it's simply not worth the time and expense for the typical clinical questions that we ask. Supporters of CERs argue that they offer the chance to produce high-powered evidence faster, cheaper and more efficiently.