Systemic therapy
Uitgangsvraag
Key question
What is the recommended strategy for administering systemic therapy (chemotherapy, antihormonal therapy, immunotherapy, or targeted therapy) in patients with spinal metastases to prevent neurologic deficits and pain, and to optimize quality of life?
Aanbeveling
Recommendations
- Always discuss the indications for local or systemic therapy in a multidisciplinairy team meeting with the organ specialist concerned, see also module Multidisciplinary consultation (MDO).
- Apply systemic therapy instead of local treatment in patients with a primary malignancy, if a rapid tumor response is expected.
- Decide whether to continue systemic therapy during radiotherapy for vertebral metastases in a multidisciplinary team meeting or in consultation between the radiation oncologist and the organ-specific specialist when in doubt.
- Initiate systemic therapy immediately if disease elsewhere in the body requires it, ensuring that the therapy is proven effective against vertebral metastases and that the patient is in sufficient condition to receive it. Take into account the patient’s wishes, needs, capabilities, and limitations, and discuss treatment preferences and boundaries. Additional local therapy can still be discussed within the multidisciplinairy team meeting.
Overwegingen
Considerations
Balance between desired and undesired effects
Systemic treatment is generally not the first choice of treatment for neurological deficits caused by MESCC, considering: the fact that both research and clinical practice show that radiotherapy and surgery are effective for neurological deficits caused by MESCC due to epidural spread of spinal metastases and the limited evidence of the effect of systemic therapy.
In patients with therapy-sensitive tumors such as malignant lymphoma, multiple myeloma, breast cancer, prostate cancer, some types of lung cancers, and testicular cancer, systemic treatment can be used as the first choice in case of neurological deficits due to MESCC:
- where there is a significant chance of a very rapid effect from chemotherapy (especially in multiple myeloma, non-Hodgkin lymphoma of intermediate or high malignancy, and metastatic germ cell tumors); and/or
- there is a vital indication for systemic therapy based on the disease elsewhere in the body that cannot be delayed until after radiotherapy or surgery; and/or
- there are no further options for radiotherapy and surgery.
In the case of therapy-sensitive tumors, chemotherapy and antihormonal therapy can lead to a reduction of pain related to bone metastases, and thus also to an improvement in the quality of life. This assumption is particularly supported by clinical research in metastatic prostate carcinoma (Crawford, 2015; Jong, 2016). There is no reason to suspect that spinal metastases would respond differently to systemic treatment than other bone metastases.
Targeted therapy can have a rapid effect and is therefore preferred if there is a possibility of systemic therapy based on molecular diagnostics. However, in the case of a new diagnosis, molecular diagnostics can take up to three weeks (see module Diagnostics). Radioisotope therapy is an option for breast cancer and castratie-resistant prostate cancer with effect within one to four weeks. With immunotherapy, the response can only be determined after weeks to three months.
Treatment of primary diseases from the bone marrow (myeloma) such as osseous lymphoma and multiple myeloma is always chemo/immunotherapy and/or targeted therapy (except solitary plasmacytoma). Radiotherapy is only mentioned in the lymphoma treatment guidelines as primarily post-systemic therapy and not before or during. Radiotherapy is described in the multiple myeloma treatment guidelines in specific situations: curative in solitary plasmacytoma and palliative in multiple myeloma. Because systemic therapy is becoming increasingly effective and more resources are becoming available resulting in longer survival, radiotherapy can also play a role in the context of long-term local control of symptomatic lesions. Given that patients often require multiple lines of systemic therapy, radiotherapy should be as bone marrow sparing as possible and be implemented at the right time. No data is based on randomized studies.
Quality of Evidence
The overall quality of evidence is very low. This indicates that we are highly uncertain about the estimated effects of the critical outcomes. Downgrading was applied due to the observational nature of the studies, which entails a risk of bias, and due to wide confidence intervals (imprecision).
Patient Values and Preferences (and those of caregivers, where applicable)
It is important to discuss possible side effects and expected prognosis with the patient. Local treatment or choosing not to treat with systemic therapy, in order to improve quality of life, may also be considered.
Cost Considerations
Systemic therapy is used for purposes beyond the treatment of spinal metastases alone. Therefore, the role of costs in this context is unclear.
Equity (Health Equity / Equitable Access)
All therapies described are registered and covered, and reimbursement is not a limiting factor in this setting.
Acceptability – Ethical Acceptability
There are no known ethical objections to any of the systemic therapies discussed in this module.
Sustainability
Sustainability aspects do not play a role in the prescription of systemic therapy within the Dutch healthcare context.
Feasibility
There are no limitations concerning the availability of systemic therapy. All systemic treatments are equally available in the Dutch healthcare context.
Onderbouwing
Background
In the 2015 guideline, only chemotherapy and antihormonal therapy are described as systemic treatment options for spinal metastases. However, at present several new systemic anti-tumor therapies have become available, including targeted therapy, radiopharmaceuticals, and immunotherapy.
In patients with symptomatic spinal metastases, a multidisciplinary consultation with a neurologist, radiation oncologist organ specialist and spine surgeon is conducted to assess the need and urgency of local treatment. A careful assessment must then be made regarding the preference for local or systemic treatment.
The preferred systemic treatment is determined by the primary tumor type and tumor characteristics. Both the expected response rate and time to tumor response depend on the tumor type, the degree of instability, epidural extension and compression of neural tissue are critical in guiding treatment decisions.
Based on prior knowledge, there are certain types of malignancies such as melanoma, lymphoma and multiple myeloma which are expected to respond quickly to systemic therapy.
Summary of Findings
Systematic therapy compared to no systematic therapy for patients with spinal metastases
Population: Patients with asymptomatic spinal metastases
Intervention: Systematic therapy (chemotherapy, anti-hormonotherapy, immunotherapy, targeted therapy)
Comparator: No systematic therapy
|
Outcome
|
Study results and measurements |
Absolute effect estimates |
Certainty of the Evidence (Quality of evidence) |
Conclusions |
|
|
Systematic therapy |
No systematic therapy |
||||
|
Neurological failure for patients with symptoms (critical) |
- |
- |
- |
- |
No evidence was found regarding the effect of systematic therapy when compared with no systematic therapy in patients with spinal metastases. |
|
Skeletal related events for asymptomatic patients (critical) |
- |
- |
- |
- |
No evidence was found regarding the effect of systematic therapy when compared with no systematic therapy in patients with spinal metastases. |
|
|
|||||
|
Overall survival (important)
|
Chemotherapy Hazard ratio (95%CI): 0.6 (0.2 – 1.5)
Based on data from 1319 participants in 1 systematic review |
Chemotherapy: (Median in months) 14.2 (5.5–19.9) |
No chemotherapy: (Median in months) 8.5 (4.6–11.0) |
Very low Due to observational evidence1, due to serious imprecision2
|
The evidence is very uncertain about the effect of chemotherapy on overall survival when compared with no chemotherapy in patients with spinal metastases. (Gillespie 2023) |
|
Difference: not reported |
|||||
|
Targeted therapy Hazard ratio (95%CI): 0.4 (0.2 – 0.5)
Based on data from 1885 participants in 1 systematic review |
Targeted therapy: (Median in months) Lung: 21.4 (11.0–23.6) Breast: 83.2 (53.0–94.2) |
No targeted therapy: (Median in months) Lung: 5.7 (4.0-10.9) Breast: 32.9 (25.0–54.3) |
Low Due to observational evidence1 |
The evidence suggests targeted therapy improves overall survival when compared with no targeted therapy in patients with spinal metastases from primary lung or breast cancer. (Gillespie 2023) |
|
|
Difference: not reported |
|||||
|
Quality of life (important) |
- |
- |
- |
No evidence was found regarding the effect of systematic therapy when compared with no systematic therapy in patients with spinal metastases. |
|
|
Pain relief (important)
|
- |
- |
- |
No evidence was found regarding the effect of systematic therapy when compared with no systematic therapy in patients with spinal metastases. |
|
1. Due to observational evidence, the quality of evidence begins as low.
2. Risk of Bias: serious. No additional downgrading was applied, as the quality of evidence was already rated as low due to its observational nature.
3. Imprecision: serious. Due to overlap of the upper limit of the 95% confidence interval with the minimal clinically important difference (Downgraded by one level).
Summary of literature
Description of studies
A total of one study was included in the analysis of the literature. Important study characteristics and results are summarized in table 2. The assessment of the risk of bias is evaluated in the original systematic review.
Table 2. Characteristics of included studies
|
Study |
Participants |
Comparison |
Follow-up |
Outcome measures and effect size |
RoB/Comments |
|
Groszman, 2024 |
Patients with a pathology of spinal cord metastases secondary to lung cancer, breast cancer, bone cancer, GI cancer, prostate cancer, thyroid cancer, melanoma, or kidney cancer.
Eligibility criteria: Present an original article reporting a case series greater than 5 patients: RCTs, clinical case series Exclusion criteria: 1) A pathology of inflammation, infection, or trauma. 2) Case reports, reviews, abstracts, editorials, letters, and duplicate studies or repeat publications of the same patient group; non-English papers; and papers published before 2005.
N at baseline Lung n=2137 Breast n=591 Renal n=167 Melanoma n=321 Thyroid n=22
Age (weighted mean in years) Lung 58.3 Breast 58.3 Renal 61.9 Melanoma 56.3 Thyroid 58.1
Sex (Male, n(%)) Lung 1299 (60.8) Breast 3 (0.5) Renal 124 (74.2) Melanoma Not reported Thyroid 3 (13.6)
Pooled median OS (months, 95%CI) Lung 6.7 (4.8-11.6) Breast 28.3 (18.0-159.8) Renal 58.3 (23.6-100.0) Melanoma 10.6 (3.9-18.0) Thyroid 123.0 (not reported) |
Patients undergoing surgery, radiation therapy, targeted therapy, chemotherapy treatment, bisphosphonate therapy, immunotherapy, or no treatment for their spinal cord metastases
|
Not reported |
Life expectancy based on survivorship and prognostic factors specific to patients with spinal cord metastases |
Risk of bias was evaluated in the systematic review using the Cochrane Collaboration’s tool. Due to potential bias arising from the randomization process, and due to deviations from intended intervention, and some concern about missing outcome data in most of the included studies, the risk of bias was considered to be “some concern”. |
Results
Groszman (2024) reported the outcome of overall survival (Table 3).
Table 3. Results of overall survival
|
|
Primary cancer |
No. patients
|
Median OS 95%CI (months) |
HR (95%CI) |
Clinically relevance |
|||
|
Yes |
No |
Yes |
No |
|||||
|
Chemotherapy |
Lung |
598 |
721 |
14.2 (5.5-19.9) |
8.5 (4.6-11.0) |
0.604 (0.248-1.467) P= 0.265 |
Not sufficient |
|
|
Targeted therapy |
Lung |
717 |
1168 |
21.4 (11.0-23.6) |
5.7 (4.0-10.9) |
0.395 (0.296-0.527) P< 0.0001 |
Relevant |
|
|
Breast |
191 |
166 |
83.2 (53.0-94.2) |
32.9 (25.0-54.3) |
Not reported |
Possibly relevant |
||
Search and select
A systematic review of the literature was performed to answer the following question(s):
What are the benefits and risks of systemic treatment compared with no systemic treatment (best supportive care or locoregional treatment) for patients with spinal metastases?
Table 1. PICO
| Patients |
Patiënten met wervelmetastasen (alleen asymptomatisch of symptomatisch maar zonder dreigende myelumcompressie, of reeds bestaande neurologische uitval) |
| Intervention |
Systemische therapie (chemotherapie, antihormonale therapie, immuuntherapie of doelgerichte therapie, type afhankelijk van type tumor |
| Control | Geen systemische therapie (best supportive care of locoregionale behandeling [chirurgische/radiotherapeutische interventies]) |
| Outcomes |
Bij symptomatische populatie: neurologische uitval (critical), Bij asymptomatische populatie: SRE (skeletal related events, critical) Pijn (important), kwaliteit van leven (important), overleving (important) |
Relevant outcome measures
The guideline panel considered neurological deficits (in the symptomatic population) and SREs (in the asymptomatic population) as critical outcome measures for decision-making, and pain, quality of life, and survival as important outcome measures for decision-making.
Definitions and thresholds
|
Outcome |
Definition |
Threshold |
|
Neurological failure (critical outcome measure) |
As defined in the used studies |
RR: 1.25/0.80 0,5SD |
|
SRE (critical outcome measure) |
Including fractures, MSCC, local intervention required, as defined in the used studies |
RR: 1.25/0.80 0,5SD |
|
Overall survival (important outcome measure) |
As defined in the used studies |
HR: 0.7/1.4; 12/16 week depending on life of expectancy
|
|
Pain relief/pain response (important outcome measure) |
As defined in the used studies |
20% (i.e. 2 punten VAS/NRS (0-10)) |
|
Quality of life (important outcome measure) |
As defined in the used studies |
EQ-5D: >0.08 points EQ-5D VAS: > 7 points (Pickard, 2007) |
Search and select (Methods)
A systematic literature search was performed by a medical information specialist using the following bibliographic databases: Embase.com and Ovid/Medline. Both databases were searched from 2014 to 24 Juni 2024 for systematic reviews, RCTs and observational studies. Systematic searches were completed using a combination of controlled vocabulary/subject headings (e.g., Emtree-terms, MeSH) wherever they were available and natural language keywords. The overall search strategy was derived from two primary search concepts: (1) spinal metastases; (2) systemic therapy (chemotherapy, antihormonal therapy, immunotherapy, and targeted therapy). Duplicates were removed using EndNote software. After deduplication a total of 2065 records were imported for title/abstract screening. Initially, 40 studies were selected based on title and abstract screening. After reading the full text, 39 studies were excluded (see the exclusion table under the tab ‘Evidence tabellen’), and one systematic review was included.
- 1 - Crawford DE, Higano CS, Shore ND, Hussain M, Petrylak DP. Treating patients with metastatic castration resistant prostate cancer: a comprehensive review of available therapies. J Urol 2015; 194: 1537-47.
- 2 - Groszman L, Hubermann JA, Kooner P, Alamiri N, Bozzo A, Aoude A. The impact of adjunct medical therapy on survival after spine metastasis: a systematic review and pooled data analysis. Cancers. 2024 Apr 7;16(7):1425.
- 3 - Jong JM, Oprea-Lager DE, Hooft L, de Klerk JM, Bloemendal HJ, Verheul HM, Hoekstra OS, van de Eertweghe AJ. Radiopharmaceuticals for palliation of bone pain in patients with castration-resistant prostate cancer metastatic to bone: a systematic review. Eur Urol 2016; 70: 416-26.
Evidence tables
Not applicable.
Table of excluded studies
|
No |
Reference |
Reason for exclusion |
|
1. |
Bone Metastases of Gastrointestinal Stromal Tumor: A Review of Published Literature |
Ongewenste vergelijking |
|
2. |
Comparative Efficacy of Combined Radiotherapy, Systemic Therapy, and Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer: A Network Meta-Analysis and Systematic Review |
Ongewenste populatie |
|
3. |
Current paradigms for metastatic spinal disease: An evidence-based review |
Ongewenste vergelijking |
|
4. |
Current progress and mechanisms of bone metastasis in lung cancer: A narrative review |
Ongewenste opzet |
|
5. |
Epidemiology, management, and treatment outcomes of metastatic spinal melanoma |
Ongewenste opzet |
|
6. |
The importance of surgery as part of multimodal therapy in rapid progressive primary extraosseous ewing sarcoma of the cervical intra- and epidural space |
Ongewenste populatie |
|
7. |
Intramedullary Spinal Metastatic Renal Cell Carcinoma: Systematic Review of Disease Presentation, Treatment, and Prognosis with Case Illustration |
Ongewenste vergelijking |
|
8. |
Non-surgical ablative treatment of distant extracranial metastases for renal cell carcinoma: A systematic review |
Ongewenste vergelijking |
|
9. |
An Overview of Decision Making in the Management of Metastatic Spinal Tumors |
Ongewenste opzet |
|
|
Pancreatic Cancer Metastasis to the Spine: A Systematic Review of Management Strategies and Outcomes with Case Illustration |
Ongewenste vergelijking |
|
|
Recent advances and new discoveries in the pipeline of the treatment of primary spinal tumors and spinal metastases: a scoping review of registered clinical studies from 2000 to 2020 |
Ongewenste vergelijking |
|
|
Spinal cord compression in cancer patients |
Ongewenste taal |
|
|
A systematic review of clinical outcomes for patients diagnosed with skin cancer spinal metastases |
Ongewenste vergelijking |
|
|
A Systematic Review of Metastatic Hepatocellular Carcinoma to the Spine |
Ongewenste vergelijking |
|
|
Thyroid carcinoma metastases to central nervous system and vertebrae |
Ongewenste uitkomst |
|
|
Treatment of spinal metastases in renal cell carcinoma: A critical review |
Ongewenste opzet |
|
|
Treatment strategy for vertebral metastases from anal squamous cell carcinoma: a comprehensive literature review and case report |
Ongewenste opzet |
|
|
Advances in the treatment of metastatic spine tumors: The future is not what it used to be |
Ongewenste opzet |
|
|
How I treat metastatic prostate cancer |
Ongewenste populatie |
|
|
A New Treatment Strategy for Spinal Metastasis: The "Systemic Conditions, Effectiveness of Systemic Treatment, Neurology, and Oncology" Decision Framework System |
Ongewenste vergelijking |
|
|
Spinal Metastases and the Evolving Role of Molecular Targeted Therapy, Chemotherapy, and Immunotherapy |
Ongewenste vergelijking |
|
|
Trastuzumab Deruxtecan (Enhertu): CADTH Reimbursement Recommendation: Indication: For the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received at least 1 prior line of chemotherapy in the metastatic setting or developed disea... |
Ongewenste populatie |
|
|
Case Series: "silent" Spinal Epidural Metastases in Metastatic Castrate-Resistant Prostate Cancer |
Ongewenste opzet |
|
|
Impact of intense systemic therapy and improved survival on the use of palliative radiotherapy in patients with bone metastases from prostate cancer |
Ongewenste vergelijking |
|
|
The Impact of Targetable Mutations on Clinical Outcomes of Metastatic Epidural Spinal Cord Compression in Patients With Non–Small-Cell Lung Cancer Treated With Hybrid Therapy (Surgery Followed by Stereotactic Body Radiation Therapy) |
Ongewenste opzet |
|
|
Safety and clinical efficacy of immune checkpoint inhibition and stereotactic body radiotherapy in patients with spine metastasis |
Ongewenste opzet |
|
|
Camrelizumab Plus Zoledronic Acid Showed Sustained Efficacy in A Patient with Cranial and Spinal Metastases from Lung Adenocarcinoma |
Ongewenste opzet |
|
|
The Evolving Treatment Paradigm for Metastatic Spine Disease |
Ongewenste vergelijking |
|
|
Prospective comparison of one-year survival in patients treated operatively and nonoperatively for spinal metastatic disease: results of the prospective observational study of spinal metastasis treatment (POST) |
Ongewenste vergelijking |
|
|
Systemic therapy with or without local intervention for oligometastatic oesophageal squamous cell carcinoma (ESO-Shanghai 13): an open-label, randomised, phase 2 trial |
Ongewenste populatie |
|
|
Targeted treatments of bone metastases in patients with lung cancer |
Ongewenste vergelijking |
|
|
Bone Metastases in Non-Seminomatous Germ Cell Tumors: A 20-Year Retrospective Analysis |
Ongewenste vergelijking |
|
|
Effect of Immunotherapy Status on Outcomes in Patients with Metastatic Melanoma to the Spine |
Ongewenste vergelijking |
|
|
Management of neoplastic spinal tumors in a spine surgery care unit |
Ongewenste vergelijking |
|
|
Metastatic Lesions of the Brain and Spine |
Ongewenste opzet |
|
|
Metastatic Renal Cell Carcinoma to the Spine: Outcomes and Morbidity: Single-Center Experience |
Ongewenste vergelijking |
|
|
Non-operative management of spinal metastases: A prognostic model for failure |
Ongewenste vergelijking |
|
|
Ten-year trends in the treatment and intervention timing for patients with metastatic spinal tumors: a retrospective observational study |
Ongewenste vergelijking |
|
|
Overall survival and prognostic factors in patients with spinal metastases from lung cancer treated with and without epidermal growth factor receptor tyrosine kinase inhibitors. |
Geïncludeerd in de systematische review |
Beoordelingsdatum en geldigheid
Publicatiedatum : 05-06-2026
Beoordeeld op geldigheid : 05-06-2026
Algemene gegevens
De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd door de Stichting Kwaliteitsgelden Medisch Specialisten (SKMS). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.
Samenstelling werkgroep
Voor het ontwikkelen van de richtlijnmodule is in 2023 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor patiënten met wervelmetastasen.
Werkgroep
- dr. W. (Walter) Taal (voorzitter), neuroloog Erasmuc MC, Nederlandse Vereniging voor Neurologie
- drs. L. (Lena) van Iterson, AIOS-neuroloog Elisabeth-TweeSteden Ziekenhuis, Nederlandse Vereniging voor Neurologie
- drs. R.P.B. (Robin) Boltjes, neuroloog Antoni van Leeuwenhoek Ziekenhuis, Nederlandse Vereniging voor Neurologie
- Prof. dr. JJ. (Jorrit-Jan) Verlaan, Orthopedisch chirurg UMC Utrecht, Nederlandse Orthopaedische Vereniging
- dr. J. (Jasper) van Tiel, Orthopedisch chirurg UMC Utrecht, Nederlandse Orthopaedische Vereniging
- dr. V. (Vivian) Bongers, Nucleaire geneeskunde Diakonessenhuis Utretch, Nederlandse Vereniging voor Nucleaire Geneeskunde
- Prof. dr. R. (Ronald) Bartels, Neurochirurg Radboudumc, Nederlandse Vereniging voor Neurochirurgie
- dr. S.O. (Selma) Algra, Radioloog UMC Utrecht, Nederlandse Vereniging voor Radiologie
- drs. M.G.A. (Maaike) Schippers, radiotherapeut Instituut Verbeeten, Nederlandse Vereniging voor Radiotherapie en Oncologie
- dr. J.M. (Joanne) van der Velden, radiotherapeut UMC Utrecht, Nederlandse Vereniging voor Radiotherapie en Oncologie
- dr. M.S. (Marthe) Paats, longarts Erasmus MC, Nederlandse Vereniging voor Artsen voor Longziekten en TBC
- dr. P.F. (Paula) Ypma, Internist hematoloog Haga Ziekenhuis, Nederlandse Internisten Vereniging
- dr. F.Y.F.L. (Filip) de Vos, internist-oncoloog en kaderarts palliatieve zorg UMC Utrecht, Nederlandse Internisten Vereniging
- dr. M. (Marije) Vos- van der Hulst, revalidatiearts Sint Maartenskliniek, Nederlandse Vereniging van Revalidatieartsen (vanaf oktober 2025)
- Mevr. S (Silvie) Dronkers†, patiëntvertegenwoordiger, Stichting Darmkanker (tot oktober 2025)
- dr. T.A.R. (Tebbe) Sluis†, Revalidatiearts Rijndam, Nederlandse Vereniging van Revalidatieartsen (tot mei 2025)
Klankbordgroep
- Mevr. Manon Immerzeel, Verpleegkundig specialist Reinier de Graaf ziekenhuis, Verpleegkundigen en Verzorgenden Nederland
- drs. A. (Anita) Ophof, anesthesioloog Antoni van Leeuwenhoek Ziekenhuis, Nederlandse Vereniging voor Anesthesiologie
Met dank aan
- dr. J.H. (Jurgen) Runge, interventieradioloog, UMC Groningen, Nederlandse Vereniging voor Radiologie
Met ondersteuning van
- dr. J. (Josefien) Buddeke, senior adviseur, Kennisinstituut van de Federatie Medisch Specialisten (vanaf juli 2024)
- dr. L. (Linda) Oostendorp, senior adviseur, Kennisinstituut van de Federatie Medisch Specialisten (tot juli 2024)
- drs. B. (Beatrix) Vogelaar, adviseur, Kennisinstituut van de Federatie Medisch Specialisten
- dr. J. (Jing) de Haan-Du, adviseur, Kennisinstituut van de Federatie Medisch Specialisten
- drs. D. (Danique) Middelhuis, adviseur, Kennisinstituut van de Federatie Medisch Specialisten
- drs. A. (Alies) Oost, informatiespecialist, Kennisinstituut van de Federatie Medisch Specialisten
Belangenverklaringen
Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten via secretariaat@kennisinstituut.nl.
Gemelde (neven)functies en belangen werkgroep
|
Naam WERKGROEP |
Hoofdfunctie |
Nevenwerkzaamheden |
Persoonlijke Financiele_Belangen |
Persoonlijke Relaties |
Extern Gefinancierd Onderzoek |
Intellectuele Belangen Reputatie |
Overige Belangen |
Datum |
Acties |
|
Jasper van Tiel |
Orthopedisch chirurg UMC Utrecht en Acibadem IMC |
geen |
geen |
geen |
geen |
geen |
geen |
22-11-2023 |
Geen restrictie |
|
Joanne van der Velden |
Radiotherapeut bij het UMC Utrecht, betaald |
Bestuurslid bij het Landelijk Platform Palliatieve Radiotherapie (NVRO), onbetaald |
Geen |
Geen |
Deelname aan 2 extern gefinancierde onderzoeken, zie onder |
Verwerven van erkenning speelt mee aan mijn deelname aan de werkgroep richtlijn Wervelmetastasen |
Geen overige belangen |
28-12-2023 |
Geen restrictie |
|
Jorrit-Jan Verlaan |
Orthopedisch chirurg, UMC Utrecht (0.4 Fte) |
Lid steering committee AO Spine Knowledge Forum Tumor (onbetaald maar met onkosten vergoeding). |
Hoe de richtlijn wordt vormgegeven staat los van mijn persoonlijke financiële belangen. Er zijn ook geen belangen voor SentryX hoe de richtlijn wordt vormgegeven. |
geen |
Ja. |
Ik heb nationale/internationale expertise/reputatie en een leerstoel op het gebied van de behandeling van wervelmetastasen. Een goed uitgevoerde richtlijn kan helpen deze expertise/reputatie meer exposure te geven maar de impact en eventuele belangenverstrengeling zijn mij onduidelijk. |
geen |
22-11-2023 |
Geen restrictie. Geen penvoerder bij module 'Inschatten overleving'. |
|
Filip de Vos |
Internist-oncoloog en kaderarts palliatieve zorg |
geen |
geen |
geen |
ja |
geen |
BMS Advisory Board; Faculty member ESMO CNS tumors; Quality of Care commission Dutch Society of Medical Oncology; |
20-12-2023 |
Geen restrictie. (In de richtlijn worden geen systemische therapien aanbevolen.) |
|
Maaike Schippers |
Radiotherapeut |
geen |
geen |
geen |
geen |
geen |
geen |
3-12-2023 |
Geen restrictie |
|
Marthe Paats |
Longarts Erasmus MC |
geen |
Geen relevant voor huidige richtlijn. |
geen |
industrie gesponsorde studies lopend in het Erasmus MC waarbij ik lokale PI ben. |
geen |
geen |
26-02-2024 |
Geen restrictie. In de richtlijn worden geen systemische therapien aanbevolen. |
|
Robin Boltjes |
Neuroloog in Antoni van Leeuwenhoek/NKI |
geen |
geen |
nee |
geen |
geen |
nee |
22-11-2023 |
Geen restrictie |
|
Ronald Bartels |
Neurochirurg |
Medisch Adviseur |
geen |
nee |
geen |
net |
geen |
03-04-2024 |
Restrictie ten aanzien van besluitvorming betreffende 'Inschatten overleving'. Vanuit expertise wel meegediscussierd over inhoud van de module, niet betrokken bij het formuleren van de aanbevelingen. |
|
Tebbe Sluis |
revalidatiearts |
geen |
geen |
geen |
geen |
geen |
geen |
11-12-2023 |
Geen restrictie |
|
Vivian Bongers |
MSB Domstad, medisch specialist |
Uitgeverij Prelum, Redacteur tijdschrift IMAGO |
Geen |
Geen |
Geen |
Geen |
Geen |
23-11-2023 |
Geen restrictie |
|
Ypma |
internist hematoloog Hagaziekenhuis den Haag |
geen |
geen |
geen |
Alphabet trial |
geen |
nvt |
04-05-2024 |
Geen restrictie |
|
Van Iterson |
AIOS neurologie |
geen |
geen |
geen |
geen |
geen |
geen |
25-04-2024 |
Geen restrictie |
|
Selma Algra |
Radioloog,St Jansdal Ziekenhuis |
geen |
geen |
geen |
geen |
geen |
geen |
03-09-2024 |
Geen resctrictie |
|
Silvie Dronkers |
Stichting Darmkanker |
geen |
geen |
geen |
geen |
geen |
geen |
06-02-2025 |
Geen restrictie |
|
Walter Taal (voorzitter) |
Neuroloog, Erasmus MC, Rotterdam |
Geen |
Geen |
Geen |
Ja. Alleen op het gebied van neurofibromatose type 1 |
Geen |
Geen |
07-06-2023 |
Geen restrictie |
|
Marije Vos-van der Hulst |
Revalidatie arts, Sint Maartenskliniek Nijmegen |
Voorzitter werkgroep revalidatie artsen dwarslaesie (Nederlands Vlaams dwarslaesie genootschap= werkgroep van de vereniging revalidatieartsen nederland (VRA)) |
geen |
geen |
geen |
geen |
geen |
13-10-2025 |
Geen restrictie |
|
Naam KLANKBORDGROEP |
Hoofdfunctie |
Nevenwerkzaamheden |
Persoonlijke Financiele_Belangen |
Persoonlijke Relaties |
Extern Gefinancierd Onderzoek |
Intellectuele Belangen Reputatie |
Overige Belangen |
Datum |
Acties |
|
Manon Immerzeel |
Deelnemer clusterstuurgroep |
Geen |
Geen |
Geen |
Geen |
Voorzitter in het bestuur van V&VN pijnverpleegkundigen |
Neen |
22-03-2022 |
Geen restrictie |
|
Anita Ophof |
Antoni van Leeuwenhoek Ziekenhuis |
Geen |
Geen |
Geen |
Geen |
Geen |
Geen |
01-05-2025 |
Geen restrictie |
Inbreng patiëntenperspectief
Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz
Bij de richtlijnmodule voerde de werkgroep conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uit om te beoordelen of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling is de richtlijnmodule op verschillende domeinen getoetst (zie het stroomschema bij Werkwijze).
De kwalitatieve raming is toegevoegd aan het einde van elke herziene module.
| Module | Uitkomst raming | Toelichting |
| Systemic therapy | Geen substantiële financiële gevolgen | Hoewel uit de toetsing volgt dat de aanbevelingen breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft. Er worden daarom geen substantiële financiële gevolgen verwacht. |
Werkwijze
Voor meer details over de gebruikte richtlijnmethodologie verwijzen wij u naar de Werkwijze. Relevante informatie voor de ontwikkeling/herziening van deze richtlijnmodule is hieronder weergegeven.
Zoekverantwoording
Zoekstrategie
Embase.com
|
No. |
Query |
Results |
|
#1 |
'spine metastasis'/exp OR 'spinal cord metastasis'/exp OR 'cervical lymph node metastasis'/exp OR (('spinal cord tumor'/exp OR 'spine tumor'/exp OR 'spinal cord compression'/exp OR (((spinal* OR medulla*) NEAR/3 (compress* OR impingement OR pinch*)):ti,ab,kw)) AND ('metastasis'/de OR 'bone metastasis'/de OR metasta*:ti,ab,kw OR oligometasta*:ti,ab,kw OR micrometasta*:ti,ab,kw OR (((neoplas* OR carcinoma OR cancer* OR malignan* OR tumor* OR tumour*) NEAR/4 (dissemination OR disseminated OR spread* OR secondary OR migrat* OR seed*)):ti,ab,kw))) OR (((spine* OR spinal* OR intraspinal OR vertebr* OR 'cauda equina' OR cervicothoracic OR cord* OR coccyx OR duralsac* OR 'dural sac*' OR epidural OR extradural OR 'extra dural' OR intervertebr* OR lumbar OR lumbosac* OR 'lumbo sac*' OR orthothoracic OR sacral OR sacrum OR 'thecal sac*' OR thoracolumbar OR odontoid OR 'anterior horn' OR 'posterior horn' OR 'extrapyramidal tract*' OR 'pyramidal tract*' OR 'substantia gelatinosa' OR 'spinothalamic tract*') NEAR/4 (metast* OR oligometast* OR micrometast*)):ti,ab,kw) OR ((cervical*:ti,ab,kw OR medulla*:ti,ab,kw OR intramedulla*:ti,ab,kw OR thoracic:ti,ab,kw) AND (spine*:ti,ab,kw OR spinal*:ti,ab,kw OR intraspinal:ti,ab,kw OR vertebr*:ti,ab,kw OR intervertebr*:ti,ab,kw OR lumbar:ti,ab,kw) AND (metast*:ti,ab,kw OR oligometast*:ti,ab,kw OR micrometast*:ti,ab,kw)) OR mescc:ti,ab,kw OR mscc:ti,ab,kw |
29214 |
|
#2 |
'systemic therapy'/exp OR ((systemic NEAR/3 (therap* OR treatment*)):ti,ab,kw) OR 'chemotherapy'/exp OR chemo:ti,ab,kw OR 'chemotherap*':ti,ab,kw OR chemoimmuno*:ti,ab,kw OR electrochemo*:ti,ab,kw OR 'cytostatic agent'/exp OR 'cytostatic*':ti,ab,kw OR 'anthracycline antibiotic agent'/exp OR anthracyclin*:ti,ab,kw OR 'alkylating agent'/exp OR alkylat*:ti,ab,kw OR 'cancer immunotherapy'/exp OR immunotherap*:ti,ab,kw OR 'immuno* therap*':ti,ab,kw OR immunetherap*:ti,ab,kw OR 'immune therap*':ti,ab,kw OR 'immune checkpoint inhibitor'/exp OR (((checkpoint* OR 'check point*' OR immunocheckpoint*) NEAR/3 (inhibit* OR block* OR therap*)):ti,ab,kw) OR 'molecular therapy'/exp OR (((molecular* OR targeted OR tailored) NEAR/3 (therap* OR treatment*)):ti,ab,kw) OR 'personalized medicine'/exp OR (((personalize* OR personalise* OR individualize* OR individualise* OR precision) NEAR/3 (therap* OR oncotherap* OR medicine OR oncomedicine OR treatment* OR oncolog*)):ti,ab,kw) OR 'cancer hormone therapy'/exp OR 'hormonal therapy'/de OR 'antiandrogen therapy'/exp OR 'antineoplastic hormone agonists and antagonists'/exp OR 'hormone receptor'/exp OR (((antineoplastic* OR 'anti neoplastic*') NEAR/3 hormon*):ti,ab,kw) OR antiandrogen*:ti,ab,kw OR antiestrogen*:ti,ab,kw OR antioestrogen*:ti,ab,kw OR (((hormon* OR antihormon* OR endocrin* OR androgen* OR estrogen* OR oestrogen* OR progesteron*) NEAR/3 (drug* OR agent* OR medication* OR therap* OR treatment* OR receptor* OR block* OR antagonist*)):ti,ab,kw) |
3440295 |
|
#3 |
#1 AND #2 NOT ('conference abstract'/it OR 'editorial'/it OR 'letter'/it OR 'note'/it) NOT (('animal'/exp OR 'animal experiment'/exp OR 'animal model'/exp OR 'nonhuman'/exp) NOT 'human'/exp) |
6840 |
|
#4 |
#3 AND [2014-2024]/py |
4130 |
|
#5 |
'meta analysis'/exp OR 'meta analysis (topic)'/exp OR metaanaly*:ti,ab OR 'meta analy*':ti,ab OR metanaly*:ti,ab OR 'systematic review'/de OR 'cochrane database of systematic reviews'/jt OR prisma:ti,ab OR prospero:ti,ab OR (((systemati* OR scoping OR umbrella OR 'structured literature') NEAR/3 (review* OR overview*)):ti,ab) OR ((systemic* NEAR/1 review*):ti,ab) OR (((systemati* OR literature OR database* OR 'data base*') NEAR/10 search*):ti,ab) OR (((structured OR comprehensive* OR systemic*) NEAR/3 search*):ti,ab) OR (((literature NEAR/3 review*):ti,ab) AND (search*:ti,ab OR database*:ti,ab OR 'data base*':ti,ab)) OR (('data extraction':ti,ab OR 'data source*':ti,ab) AND 'study selection':ti,ab) OR ('search strategy':ti,ab AND 'selection criteria':ti,ab) OR ('data source*':ti,ab AND 'data synthesis':ti,ab) OR medline:ab OR pubmed:ab OR embase:ab OR cochrane:ab OR (((critical OR rapid) NEAR/2 (review* OR overview* OR synthes*)):ti) OR ((((critical* OR rapid*) NEAR/3 (review* OR overview* OR synthes*)):ab) AND (search*:ab OR database*:ab OR 'data base*':ab)) OR metasynthes*:ti,ab OR 'meta synthes*':ti,ab |
1039560 |
|
#6 |
'clinical trial'/exp OR 'randomization'/exp OR 'single blind procedure'/exp OR 'double blind procedure'/exp OR 'crossover procedure'/exp OR 'placebo'/exp OR 'prospective study'/exp OR rct:ab,ti OR random*:ab,ti OR 'single blind':ab,ti OR 'randomised controlled trial':ab,ti OR 'randomized controlled trial'/exp OR placebo*:ab,ti |
4056716 |
|
#7 |
'major clinical study'/de OR 'clinical study'/de OR 'case control study'/de OR 'family study'/de OR 'longitudinal study'/de OR 'retrospective study'/de OR 'prospective study'/de OR 'comparative study'/de OR 'cohort analysis'/de OR ((cohort NEAR/1 (study OR studies)):ab,ti) OR (('case control' NEAR/1 (study OR studies)):ab,ti) OR (('follow up' NEAR/1 (study OR studies)):ab,ti) OR (observational NEAR/1 (study OR studies)) OR ((epidemiologic NEAR/1 (study OR studies)):ab,ti) OR (('cross sectional' NEAR/1 (study OR studies)):ab,ti) |
8288309 |
|
#8 |
'case control study'/de OR 'comparative study'/exp OR 'control group'/de OR 'controlled study'/de OR 'controlled clinical trial'/de OR 'crossover procedure'/de OR 'double blind procedure'/de OR 'phase 2 clinical trial'/de OR 'phase 3 clinical trial'/de OR 'phase 4 clinical trial'/de OR 'pretest posttest design'/de OR 'pretest posttest control group design'/de OR 'quasi experimental study'/de OR 'single blind procedure'/de OR 'triple blind procedure'/de OR (((control OR controlled) NEAR/6 trial):ti,ab,kw) OR (((control OR controlled) NEAR/6 (study OR studies)):ti,ab,kw) OR (((control OR controlled) NEAR/1 active):ti,ab,kw) OR 'open label*':ti,ab,kw OR (((double OR two OR three OR multi OR trial) NEAR/1 (arm OR arms)):ti,ab,kw) OR ((allocat* NEAR/10 (arm OR arms)):ti,ab,kw) OR placebo*:ti,ab,kw OR 'sham-control*':ti,ab,kw OR (((single OR double OR triple OR assessor) NEAR/1 (blind* OR masked)):ti,ab,kw) OR nonrandom*:ti,ab,kw OR 'non-random*':ti,ab,kw OR 'quasi-experiment*':ti,ab,kw OR crossover:ti,ab,kw OR 'cross over':ti,ab,kw OR 'parallel group*':ti,ab,kw OR 'factorial trial':ti,ab,kw OR ((phase NEAR/5 (study OR trial)):ti,ab,kw) OR ((case* NEAR/6 (matched OR control*)):ti,ab,kw) OR ((match* NEAR/6 (pair OR pairs OR cohort* OR control* OR group* OR healthy OR age OR sex OR gender OR patient* OR subject* OR participant*)):ti,ab,kw) OR ((propensity NEAR/6 (scor* OR match*)):ti,ab,kw) OR versus:ti OR vs:ti OR compar*:ti OR ((compar* NEAR/1 study):ti,ab,kw) OR (('major clinical study'/de OR 'clinical study'/de OR 'cohort analysis'/de OR 'observational study'/de OR 'cross-sectional study'/de OR 'multicenter study'/de OR 'correlational study'/de OR 'follow up'/de OR cohort*:ti,ab,kw OR 'follow up':ti,ab,kw OR followup:ti,ab,kw OR longitudinal*:ti,ab,kw OR prospective*:ti,ab,kw OR retrospective*:ti,ab,kw OR observational*:ti,ab,kw OR 'cross sectional*':ti,ab,kw OR cross?ectional*:ti,ab,kw OR multicent*:ti,ab,kw OR 'multi-cent*':ti,ab,kw OR consecutive*:ti,ab,kw) AND (group:ti,ab,kw OR groups:ti,ab,kw OR subgroup*:ti,ab,kw OR versus:ti,ab,kw OR vs:ti,ab,kw OR compar*:ti,ab,kw OR 'odds ratio*':ab OR 'relative odds':ab OR 'risk ratio*':ab OR 'relative risk*':ab OR 'rate ratio':ab OR aor:ab OR arr:ab OR rrr:ab OR ((('or' OR 'rr') NEAR/6 ci):ab))) |
15188385 |
|
#9 |
#4 AND #5 - SR |
264 |
|
#10 |
#4 AND #6 NOT #9 - RCT |
380 |
|
#11 |
#4 AND (#7 OR #8) NOT (#9 OR #10) - observationeel |
1296 |
|
#12 |
#9 OR #10 OR #11 |
1940 |
Ovid/Medline
|
# |
Searches |
Results |
|
1 |
((exp Spinal Neoplasms/ or exp Spinal Cord Neoplasms/ or exp Spinal Cord Compression/ or ((spinal* or medulla*) adj3 (compress* or impingement or pinch*)).ti,ab,kf.) and (exp Neoplasm Metastasis/ or metasta*.ti,ab,kf. or oligometasta*.ti,ab,kf. or micrometasta*.ti,ab,kf. or ((neoplas* or carcinoma or cancer* or malignan* or tumor* or tumour*) adj4 (dissemination or disseminated or spread* or secondary or migrat* or seed*)).ti,ab,kf.)) or ((spine* or spinal* or intraspinal or vertebr* or 'cauda equina' or cervicothoracic or cord* or coccyx or duralsac* or 'dural sac*' or epidural or extradural or 'extra dural' or intervertebr* or lumbar or lumbosac* or 'lumbo sac*' or orthothoracic or sacral or sacrum or 'thecal sac*' or thoracolumbar or odontoid or "Anterior Horn" or "Posterior Horn" or "Extrapyramidal Tract*" or "Pyramidal Tract*" or "Substantia Gelatinosa" or "Spinothalamic Tract*") adj4 (metast* or oligometast* or micrometast*)).ti,ab,kf. or ((cervical* or medulla* or intramedulla* or thoracic) and (spine* or spinal* or intraspinal or vertebr* or intervertebr* or lumbar) and (metast* or oligometast* or micrometast*)).ti,ab,kf. or mescc.ti,ab,kf. or mscc.ti,ab,kf. |
15129 |
|
2 |
(systemic adj3 (therap* or treatment*)).ti,ab,kf. or exp Chemoradiotherapy/ or exp Chemotherapy, Adjuvant/ or exp Consolidation Chemotherapy/ or exp Induction Chemotherapy/ or exp Maintenance Chemotherapy/ or exp Antineoplastic Combined Chemotherapy Protocols/ or chemo.ti,ab,kf. or 'chemotherap*'.ti,ab,kf. or chemoimmuno*.ti,ab,kf. or electrochemo*.ti,ab,kf. or exp Cytostatic Agents/ or 'cytostatic*'.ti,ab,kf. or exp Anthracyclines/ or anthracyclin*.ti,ab,kf. or exp Antineoplastic Agents, Alkylating/ or alkylat*.ti,ab,kf. or exp Immunotherapy/ or immunotherap*.ti,ab,kf. or 'immuno* therap*'.ti,ab,kf. or immunetherap*.ti,ab,kf. or 'immune therap*'.ti,ab,kf. or exp Immune Checkpoint Inhibitors/ or ((checkpoint* or 'check point*' or immunocheckpoint*) adj3 (inhibit* or block* or therap*)).ti,ab,kf. or exp Molecular Targeted Therapy/ or ((molecular* or targeted or tailored) adj3 (therap* or treatment*)).ti,ab,kf. or Precision Medicine/ or ((personalize* or personalise* or individualize* or individualise* or precision) adj3 (therap* or oncotherap* or medicine or oncomedicine or treatment* or oncolog*)).ti,ab,kf. or exp Antineoplastic Agents, Hormonal/ or Hormone Antagonists/ or exp Estrogen Antagonists/ or exp Androgen Antagonists/ or ((antineoplastic* or 'anti neoplastic*') adj3 hormon*).ti,ab,kf. or (antiandrogen* or antiestrogen* or antioestrogen*).ti,ab,kf. or ((hormon* or antihormon* or endocrin* or androgen* or estrogen* or oestrogen* or progesteron*) adj3 (drug* or agent* or medication* or therap* or treatment* or receptor* or block* or antagonist*)).ti,ab,kf. |
1843920 |
|
3 |
(1 and 2) not (comment/ or editorial/ or letter/) not ((exp animals/ or exp models, animal/) not humans/) |
2953 |
|
4 |
limit 3 to yr="2014 -Current" |
1433 |
|
5 |
meta-analysis/ or meta-analysis as topic/ or (metaanaly* or meta-analy* or metanaly*).ti,ab,kf. or systematic review/ or cochrane.jw. or (prisma or prospero).ti,ab,kf. or ((systemati* or scoping or umbrella or "structured literature") adj3 (review* or overview*)).ti,ab,kf. or (systemic* adj1 review*).ti,ab,kf. or ((systemati* or literature or database* or data-base*) adj10 search*).ti,ab,kf. or ((structured or comprehensive* or systemic*) adj3 search*).ti,ab,kf. or ((literature adj3 review*) and (search* or database* or data-base*)).ti,ab,kf. or (("data extraction" or "data source*") and "study selection").ti,ab,kf. or ("search strategy" and "selection criteria").ti,ab,kf. or ("data source*" and "data synthesis").ti,ab,kf. or (medline or pubmed or embase or cochrane).ab. or ((critical or rapid) adj2 (review* or overview* or synthes*)).ti. or (((critical* or rapid*) adj3 (review* or overview* or synthes*)) and (search* or database* or data-base*)).ab. or (metasynthes* or meta-synthes*).ti,ab,kf. |
754524 |
|
6 |
exp clinical trial/ or randomized controlled trial/ or exp clinical trials as topic/ or randomized controlled trials as topic/ or Random Allocation/ or Double-Blind Method/ or Single-Blind Method/ or (clinical trial, phase i or clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or controlled clinical trial or randomized controlled trial or multicenter study or clinical trial).pt. or random*.ti,ab. or (clinic* adj trial*).tw. or ((singl* or doubl* or treb* or tripl*) adj (blind$3 or mask$3)).tw. or Placebos/ or placebo*.tw. |
2741694 |
|
7 |
Epidemiologic studies/ or case control studies/ or exp cohort studies/ or Controlled Before-After Studies/ or Case control.tw. or cohort.tw. or Cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudinal.tw. or Retrospective*.tw. or prospective*.tw. or consecutive*.tw. or Cross sectional.tw. or Cross-sectional studies/ or historically controlled study/ or interrupted time series analysis/ [Onder exp cohort studies vallen ook longitudinale, prospectieve en retrospectieve studies] |
4757294 |
|
8 |
Case-control Studies/ or clinical trial, phase ii/ or clinical trial, phase iii/ or clinical trial, phase iv/ or comparative study/ or control groups/ or controlled before-after studies/ or controlled clinical trial/ or double-blind method/ or historically controlled study/ or matched-pair analysis/ or single-blind method/ or (((control or controlled) adj6 (study or studies or trial)) or (compar* adj (study or studies)) or ((control or controlled) adj1 active) or "open label*" or ((double or two or three or multi or trial) adj (arm or arms)) or (allocat* adj10 (arm or arms)) or placebo* or "sham-control*" or ((single or double or triple or assessor) adj1 (blind* or masked)) or nonrandom* or "non-random*" or "quasi-experiment*" or "parallel group*" or "factorial trial" or "pretest posttest" or (phase adj5 (study or trial)) or (case* adj6 (matched or control*)) or (match* adj6 (pair or pairs or cohort* or control* or group* or healthy or age or sex or gender or patient* or subject* or participant*)) or (propensity adj6 (scor* or match*))).ti,ab,kf. or (confounding adj6 adjust*).ti,ab. or (versus or vs or compar*).ti. or ((exp cohort studies/ or epidemiologic studies/ or multicenter study/ or observational study/ or seroepidemiologic studies/ or (cohort* or 'follow up' or followup or longitudinal* or prospective* or retrospective* or observational* or multicent* or 'multi-cent*' or consecutive*).ti,ab,kf.) and ((group or groups or subgroup* or versus or vs or compar*).ti,ab,kf. or ('odds ratio*' or 'relative odds' or 'risk ratio*' or 'relative risk*' or aor or arr or rrr).ab. or (("OR" or "RR") adj6 CI).ab.)) |
5719357 |
|
9 |
4 and 5 - SR |
83 |
|
10 |
(4 and 6) not 9 - RCT |
120 |
|
11 |
(4 and (7 or 8)) not (9 or 10) - observationeel |
394 |
|
12 |
9 or 10 or 11 |
597 |