There is an increasing need to develop high-quality evidence to support decision makers. There are many important improvements that require such big trials that they are never done. In the recent decade there has been a development to different types of pragmatic trial designs to optimize the cost-effectiveness of the trials.
In the spectrum of pragmatic trials, one of the more interesting methods is the utility of registry based randomized clinical trials. The foundation with established high-quality data-collection and longitudinal follow-up is essential.
With the rich datasets in Sweden, the ease of linkage and longitudinal quality it provides one the of the best locations for this type of research.
There are several completed and on-going R-RCT’s in Sweden that has demonstrated the ability to develop high-quality evidence. They are particularly helpful in trials to evaluate therapeutic options available in routine clinical trial.
In the previous blogpost about the fracture registry, we provided an insight to the high quality of the data. Below is a summary of the ongoing R-RCT’s within this registry. They cover from 200 up to 7000 patients and some with follow up to 10 years. This at a fraction of what a traditional trial, one of the trials has a cost of approximately 240 €/patient enrolled.
With the focus on evaluating options in clinical practice, one could argue that this is the most optimal approach for such study. There are other questions, where the traditional RCT is the favorable or even the only option.
In the DAISY trial they evaluate the role of antibiotic loaded cement vs standard of care in 7 000 patients, a trial that probably never would be carried out as a traditional trial due to the significant cost. With the R-RCT, there will be an answer at a very low cost (@1,7 million €).
- Will the HTA-evaluators and other decision makers use these types of trials to guide decisions?
Summary table comparing the trials:
|
Trial name |
Start |
Duration |
Number of patients |
|
HipSTHeR |
2019 |
10 years |
1440 |
|
Duality trial |
2020 |
5 years |
1600 |
|
SUNBURST |
2021 |
4 years |
202 |
|
Fragility Fracture |
2021 |
6 years (4 years) |
2900 |
|
DAICY |
2022 |
5 years |
7000 |
For full information about the trials, see the links to the respective protocols at the end.
Trial: DAICY
|
Indication |
Dual-impregnated antibiotic loaded cement and lower incidence of periprosthetic joint infection. |
|
Start |
2022 |
|
Estimated duration |
5 years |
|
Number of participants |
7000 patients / participants |
|
Standard of care |
Cemented hemiarthroplasty with low dose single antibiotic cement Replacement of the femoral head and neck with choice of femoral head and stem |
|
Comparator |
Cemented hemiarthroplasty with high dose dual-impregnated antibiotic cement Replacement of the femoral head and neck with choice of femoral head and stem. |
|
Allocation |
Randomization |
|
Intervention model |
Parallel assignment |
|
Primary outcome |
Periprosthetic joint infection of the index joint within one year (re-operation, or suppressive antibiotics, or combinations thereof) |
|
Secondary outcome |
|
|
Follow up |
120 days -1-year follow-up |
|
Budget |
@17 million SEK (1,7 million €) |
|
Cost per patient included |
@2 400 SEK (240 €) |
Trial: SUNBURST
|
Indication |
Thoracolumbar burst fractures without neurological deficit or complete rupture of the posterior ligament complex (PLC) |
|
Start |
2021 |
|
Estimated duration |
4 years |
|
Number of participants |
202 |
|
Standard of care |
Non-surgical |
|
Comparator |
Surgical intervention |
|
Allocation |
Randomized |
|
Intervention model |
Parallel assignment |
|
Primary outcome |
|
|
Secondary outcome |
Many including the following at 5&10 years:
|
|
Follow up |
3-4 months 1 year 5-10 years |
|
Budget |
Not possible to identify. |
|
Cost per patient included |
Not possible to identify. |
Trial: The Fragility Fracture Trial (FFT)
|
Indication |
Zoledronic acid reduction of the risk of new clinical fractures |
|
Start |
First quarter of 2021-starting with participant recruitment. |
|
Estimated duration |
6 years (4 years) |
|
Number of participants |
2900 Participants |
|
Standard of care |
Placebo (normal saline) |
|
Comparator |
Zoledronic acid (5 mg) |
|
Allocation |
Randomized, double-blind |
|
Intervention model |
Parallel assignment |
|
Primary outcome |
Time to first new clinical fracture |
|
Secondary outcome |
|
|
Follow up |
Every 6 months until 48 months 4 years of follow-up 10-year follow-up. |
|
Budget |
52,1 million SEK (5,2 million €) |
|
Cost per patient included |
18 000 sek / patient (1,800 €) |
Trial: HipSTHeR
|
Indication |
Internal fixation (hip screws) or (Hip Arthroplasty) hip replacement for undisplaced femoral neck fractures. |
|
Start |
2019 to 2029 (inclusion period 2019–2022). |
|
Estimated duration |
10 years |
|
Number of participants |
1440 older patients |
|
Standard of care |
Internal fixation |
|
Comparator |
Surgical intervention (Hip Arthroplasty) |
|
Allocation |
Randomization and no blinding |
|
Intervention model |
Parallel assignment |
|
Primary outcome |
A composite variable (reoperation rate and mortality). |
|
Secondary outcome |
|
|
Follow up |
2 years 5 years 10 years |
|
Budget |
Not possible to identify. |
|
Cost per patient included |
Not possible to identify. |
Trial: DUALITY
|
Indication |
Dual mobility cups and the reduced risk of dislocation amongst patients with displaced femoral neck fractures. |
|
Start |
The DUALITY trial started recruiting patients in January 2020 and will continue for approximately 5 years. |
|
Estimated duration |
5 years |
|
Number of participants |
1,600 patients |
|
Standard of care |
a standard cup |
|
Comparator |
dual mobility cups (DMC) |
|
Allocation |
Randomization |
|
Intervention model |
Parallel assignment |
|
Primary outcome |
the occurrence of any dislocation of the index joint treated with closed or open reduction within 1 year after surgery, |
|
Secondary outcome |
|
|
Follow up |
90 days and 1 year after surgery |
|
Budget |
Not possible to identify. |
|
Cost per patient included |
Not possible to identify. |
- Blixt, Simon, Sebastian Mukka, Peter Försth, Olof Westin, Paul Gerdhem, and on behalf of the SunBurst study Group. ‘Study Protocol: The SunBurst Trial—a Register-Based, Randomized Controlled Trial on Thoracolumbar Burst Fractures’. Acta Orthopaedica 93 (24 January 2022): 256–63. https://doi.org/10.2340/17453674.2022.1614.
- ‘Study Protocol: DAICY Trial – Dual vs. Single-Antibiotic Impregnated Cement in Hemiarthroplasty for Femoral Neck Fracture: A Registerbased Cluster-Randomized Cross-over Controlled Trial’. Accessed 10 August 2022. https://registercentrum.blob.core.windows.net/sfr/r/StudyProtocol_DAICY_220101-Sygv5OCrf9.pdf.
- ‘Study Protocol: The Fragility Fracture Trial (FFT): A Randomized, Doubleblind, Placebo-Controlled Trial to Investigate Whether Zoledronic Acid Prevents New Fractures in Older Adults with a Recent Nonhip, Non-Vertebral Fragility Fracture’. Accessed 10 August 2022. https://www.fftstudy.com/_files/ugd/3ac01b_481b5842c23640df946b27700a3e8819.pdf.
- Wolf, Olof, Sebastian Mukka, Maja Notini, Michael Möller, and Nils P Hailer. ‘Study Protocol: The DUALITY Trial—a Register-Based, Randomized Controlled Trial to Investigate Dual Mobility Cups in Hip Fracture Patients’. Acta Orthopaedica 91, no. 5 (2 September 2020): 506–13. https://doi.org/10.1080/17453674.2020.1780059.
- Wolf, Olof, Pontus Sjöholm, Nils P. Hailer, Michael Möller, and Sebastian Mukka. ‘Study Protocol: HipSTHeR - a Register-Based Randomised Controlled Trial – Hip Screws or (Total) Hip Replacement for Undisplaced Femoral Neck Fractures in Older Patients’. BMC Geriatrics 20, no. 1 (2020). https://doi.org/10.1186/s12877-020-1418-2.