The ESSKA European Allograft Initiative, tackles head on the availability, awareness and cost effectiveness of allograft tissue used for joint reconstruction in Europe. The Allograft Initiative project provides awareness within our scientific community, so we can recommend science-based options for treatment.
With the initiative ESSKA has commissioned a cost-effectiveness Health Technology Appraisal (HTA) evaluated Osteochondral allografts, Meniscal Allografts and Allografts used in ligament reconstruction. This was written by Professor Waugh and his UK team from Effective Evidence and Warwick Evidence – a group very experienced in producing information for NICE and health policy makers.
The full report is HERE.
The June edition of KSSTA contains 23 papers relating to allografts in joint reconstruction. The cost effectiveness analysis is broken down into four succinct papers (7,8,12,13) with the addition of a ‘primer’ report (14) describing the key elements of methodology in evaluating cost-effectiveness.
For each topic the ESSKA surgeons and scientist have produced peer reviewed evidence papers and 2 basic science articles. The remainder of the journal is individual research papers.
The papers are important, providing an in-depth analysis of a nominated specific treatment option. Modern results give surgeons the confidence that allograft tissue is both a viable option and a successful solution. We must balance use against risks, and the appeal of ready-made tissue may be outweighed by lack of success, failure due to processing issues or a clinical failure, making a patient worse off by complications of infection. Recycling human tissue for the benefit of reconstructing injured joints is an appealing option.
We all need to understand this vital work – determining the values of what we spend and save, the permutations of treatments, and the ‘treatment model’ that makes the computations. We need costs of treatments saved, physiotherapy input and any potential delay to knee replacement, then we can apply the modelling to each of the clinical treatment questions.
Basic Science behind allografts
The basic science of allografts - the biology of integration and the mechanical properties of allografts are analysed in two papers (2,9). The key points are:
Summary of Clinical and Cost-Effectiveness data for use of allografts
- Cell types, growth factors and cytokines coordinate in the early inflammatory and subsequent remodelling phases, and we need strategies to improve integration and survival of the allograft implants. This depends on the complex biological events at the host-implant interface.
- Mechanically, the key point is that tendon allografts are more vulnerable to overstretching in the phase of degradation compared to autografts, and this is due to a longer revascularization process that also starts later.
- That science under pins the clinical implication that grafts should tolerate high loads and that rehabilitation programs should take into account the longer time period required for full integration and maturation.
Allograft ligament reconstruction
- Information is published in clinical reviews about primary ACL reconstruction, revision ACL reconstruction and multi ligament injuries (1,6,11).
- The current review on primary ACL reconstruction (6) details the clinical results of use of non-irradiated sterilised graft tissue. Allografts are a suitable option for the older patients taking into account slower integration and the influence of chemical processing techniques.
- Caution still remains for use of allografts in the younger patient. Such patients tend to be more active and there is increasing understanding of the higher risks in this age group.
- The evidence is weak but allografts in the young are likely to carry increased risk of failure. This is an area for further comparative work.
- In PCL reconstruction and multi ligament reconstruction the clinical results of using allograft tissue appears equal based on the current available data (1,11), and therefore the choice for using allografts is based on preference and cost.
- Allografts need longer rehabilitation due to the longer maturation of allografts.
- Pure cost effectiveness analysis is not showing use of allografts in ligament surgery to be favourable.
- Graft availability and donor site morbidity determines decision making in these clinical situations.
- Cost effectiveness for osteochondral allograft transplantation (OCA) is very high (8) with the cost per quality adjusted life year (QALY) much lower than many other treatments considered for chondral and osteochondral repair.
- Graft Initial costs are higher which means potentially off putting to funders - but the excellent long-term survival translates into a much high degree of cost effectiveness. Its simple!
- Surgeons and funders need to take on board the value of such analysis when considering treatments that appear expensive at first sight but can result in very satisfactory outcomes (5).
What is next?
- It is clear that clinical data shows the high degree of clinical effectiveness of MAT with a long history (13)!
- BUT: Control data is however lacking on what happens to the patients who have symptoms after loss of meniscus but who do not get MAT.
- We know that not every patient develops early onset of intrusive symptoms after meniscectomy – we know the long-term risk of OA after meniscectomy overall but not just in the cohort of approximately 20% with early onset symptoms (4). This is an important area for further analysis.
- There is only one comparative randomised study on effectiveness available, designed as a pilot, indicating the complexity of designing randomized controlled studies in this area (10). It points towards a benefit, but longer-term data with more numbers is required, along with all the relevant costs of treatment.
- Associated chondral damage is also a confounding factor in MAT. Clinical reviews indicate a higher failure rate yet equal magnitude of gain in clinical scores where the graft survives.
- It is possible that MAT may be both less successful and more cost-effective in the more severe group because they have more to gain (13).
- What is needed is comprehensive scores such as WOMAC or SF-12, to allow costs per quality adjusted life year (QALY) need to be obtained and converted to a utility measure.
- Without treatment there may be some natural recovery or patients simply reduce activity and learn to live with the problem, and there is expense of non-MAT interventions of intensive physiotherapy or injectable biologics and these need evaluation in the post meniscectomy pathway.
- The barrier of cost has to be balanced against the gains – the basis of cost effectiveness analysis.
- Scarcity of allograft tissue throughout the European community is obvious but Allografts are an important treatment option that should be available to every patient.
- Across Europe, it appears that patients do not have allograft tissues available while superior outcome and cost effectiveness have been proven with their use. We need better provision of allografts from European Tissue banks
- For too long supply and quality has been arguably low.
The special edition of KSSTA should impress the reader with useful information – not just in the knee but also for other regions such as foot and ankle (3). The next step of the initiative is development of consensus statements by the steering group and assessment by a larger rating group. The result will be specific statements and recommendations about the use of allografts in clinical situations at European level, that can be further agreed by representative surgeons and societies around the world.
Consensus and clinical data along with cost effectiveness will be powerful in our quest for good treatment. The EAI has been a productive and collaborative effort from ESSKA in achieving change. Barriers to using specific allografts remain too high – but look, we now have the data and critics who demand this information can be answered.
- Condello V, Zdanowicz U, Di Matteo B, Spalding T, Gelber PE, Adravanti P, Heuberer P, Dimmen S, Sonnery-Cottet B, Hulet C, Bonomo M, Kon E. Allograft tendons are a safe and effective option for revision ACL reconstruction: a clinical review. Knee Surg Sports Traumatol Arthrosc. 2018 Sep 21. doi: 10.1007/s00167-018-5147-4.
- de Girolamo L, Ragni E, Cucchiarini M, van Bergen CJA, Hunziker EB, Chubinskaya S. Cells, soluble factors and matrix harmonically play the concert of allograft integration. Knee Surg Sports Traumatol Arthrosc. 2018 Oct 5. doi: 10.1007/s00167-018-5182-1.
- Diniz P, Pacheco J, Flora M, Quintero D, Stufkens S, Kerkhoffs G, Batista J, Karlsson J, Pereira H. Clinical applications of allografts in foot and ankle surgery. Knee Surg Sports Traumatol Arthrosc. 2019 Feb 5. doi: 10.1007/s00167-019-05362-0.
- Drobnič M, Ercin E, Gamelas J, Papacostas ET, Slynarski K, Zdanowicz U, Spalding T, Verdonk P. Treatment options for the symptomatic post-meniscectomy knee. Knee Surg Sports Traumatol Arthrosc. 2019 Mar 11. doi: 10.1007/s00167-019-05424-3
- Filardo G, Andriolo L, Soler F, Berruto M, Ferrua P, Verdonk P, Rongieras F, Crawford DC. Treatment of unstable knee osteochondritis dissecans in the young adult: results and limitations of surgical strategies - The advantages of allografts to address an osteochondral challenge. Knee Surg Sports Traumatol Arthrosc. 2018 Dec 6. doi: 10.1007/s00167-018-5316-5.
- Hulet C, Sonnery-Cottet B, Stevenson C, Samuelsson K, Laver L, Zdanowicz U, Stufkens S, Curado J, Verdonk P, Spalding T. The use of allograft tendons in primary ACL reconstruction. Knee Surg Sports Traumatol Arthrosc. 2019 Mar 4. doi: 10.1007/s00167-019-05440-3.
- Mistry H, Metcalfe A, Colquitt J, Loveman E, Smith NA, Royle P, Waugh N. Autograft or allograft for reconstruction of anterior cruciate ligament: a health economics perspective. Knee Surg Sports Traumatol Arthrosc. 2019 Mar 14. doi: 10.1007/s00167-019-05436-z.
- Mistry H, Metcalfe A, Smith N, Loveman E, Colquitt J, Royle P, Waugh N. The cost-effectiveness of osteochondral allograft transplantation in the knee. Knee Surg Sports Traumatol Arthrosc. 2019 Feb 5. doi: 10.1007/s00167-019-05392-8.
- Seitz AM, Dürselen L. Biomechanical considerations are crucial for the success of tendon and meniscus allograft integration-a systematic review. Knee Surg Sports Traumatol Arthrosc. 2018 Oct 5. doi: 10.1007/s00167-018-5185-y
- Smith NA, Parsons N, Wright D, Hutchinson C, Metcalfe A, Thompson P, Costa ML, Spalding T. A pilot randomized trial of meniscal allograft transplantation versus personalized physiotherapy for patients with a symptomatic meniscal deficient knee compartment. Bone Joint J. 2018; 100-B(1):56-63.
- Strauss MJ, Varatojo R, Boutefnouchet T, Condello V, Samuelsson K, Gelber PE, Adravanti P, Laver L, Dimmen S, Eriksson K, Verdonk P, Spalding T. The use of allograft tissue in posterior cruciate, collateral and multi-ligament knee reconstruction. Knee Surg Sports Traumatol Arthrosc. 2019 Mar 1. doi: 10.1007/s00167-019-05426-1.
- Waugh N, Mistry H, Metcalfe A, Colquitt J, Loveman E, Royle P, Smith NA. Knee Surg Sports Traumatol Arthrosc. 2019 Mar 22. doi: 10.1007/s00167-019-05477-4.
- Waugh N, Mistry H, Metcalfe A, Loveman E, Colquitt J, Royle P, Smith NA, Spalding T. Meniscal allograft transplantation after meniscectomy: clinical effectiveness and cost-effectiveness. (NOT YET ONLINE AND FORMATTED)
- Waugh N, Mistry H. A brief introduction to health economics. Knee Surg Sports Traumatol Arthrosc. 2019 Feb 7. doi: 10.1007/s00167-019-05372-y.
Tim Spalding1, Peter Verdonk2, Laura de Girolamo3, Romain Seil4, David Dejour5
1University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry CV2 2DX, UK.
2Antwerp Orthopaedic Center, Antwerp, Belgium
3IRCCS Orthopaedic Institute Galeazzi Ortopedico Galeazzi, Othopaedic Biotechnology Laboratory, Milano, Italy.
4Department of Orthopaedic Surgery, Clinique d'Eich-Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
5Department of Knee Surgery, Lyon OrthoClinic, Lyon, France