A. Davies - Academia.edu (original) (raw)

Papers by A. Davies

Phlebology: The Journal of Venous Disease, 2014

Endovenous techniques are, at present, the recommended choice for truncal vein treatment. However... more Endovenous techniques are, at present, the recommended choice for truncal vein treatment. However, the thermal techniques require tumescent anaesthesia, which can be uncomfortable during administration. Non-tumescent, non-thermal techniques would, therefore, have potential benefits. This randomised controlled trial is being carried out to compare the degree of pain that patients experience while receiving mechanochemical ablation or radiofrequency ablation. The early results of this randomised controlled trial are reported here. Patients attending for the treatment of primary varicose veins were randomised to receive mechanochemical ablation (ClariVein®) or radiofrequency ablation (Covidien® Venefit™). The most symptomatic limb was randomised. The primary outcome measure was intra-procedural pain using a validated visual analogue scale. The secondary outcome measures were change in quality of life and clinical scores, time to return to normal activities and work as well as the occlusion rate. One-hundred and nineteen patients have been randomised (60 in the mechanochemical ablation group). Baseline characteristics were similar. Maximum pain score was significantly lower in the mechanochemical ablation group (19.3 mm, standard deviation ±19 mm) compared to the radiofrequency ablation group (34.5 mm ± 23 mm; p < 0.001). Average pain score was also significantly lower in the mechanochemical ablation group (13.4 mm ± 16 mm) compared to the radiofrequency ablation group (24.4 mm ± 18 mm; p = 0.001). Sixty-six percent attended follow-up at one month, and the complete or proximal occlusion rates were 92% for both groups. At one month, the clinical and quality of life scores for both groups had similar improvements. Early results show that the mechanochemical ablation is less painful than the radiofrequency ablation procedure. Clinical and quality of life scores were similarly improved at one month. The long-term data including occlusion rates at six months and quality of life scores are being collected.

ABSTRACT Varicose veins are a common condition, affecting up to a quarter of the UK population. T... more ABSTRACT Varicose veins are a common condition, affecting up to a quarter of the UK population. They have been shown to negatively impact on patients' quality of life and are an important cause of morbidity. The management of varicose veins may be conservative (including lifestyle changes and compression hosiery) or surgical. Operative treatment aims to disconnect the superficial and deep venous systems at the sites of venous incompetence; traditionally saphenofemoral and saphenopopliteal junction ligation with or without stripping were the mainstay of treatment. In the last decade surgical treatment has been moving towards minimally invasive endovascular techniques, including thermal ablation (by means of radiofrequency, laser technology, steam), cryoablation and mechanochemical ablation. These are less invasive than open surgery and may be done under local anaesthesia.This article discusses the epidemiology, diagnosis and management of varicose veins, including the latest endovascular and targeted open surgical techniques such as haemodynamic surgery and variceal ablation.

Reviews in Vascular Medicine, 2016

Phlebology / Venous Forum of the Royal Society of Medicine, Jan 24, 2016

Endovenous thermal ablation has revolutionised varicose vein treatment. New non-thermal technique... more Endovenous thermal ablation has revolutionised varicose vein treatment. New non-thermal techniques such as mechanical occlusion chemically assisted endovenous ablation (MOCA) allow treatment of entire trunks with single anaesthetic injections. Previous non-randomised work has shown reduced pain post-operatively with MOCA. This study presents a multi-centre randomised controlled trial assessing the difference in pain during truncal ablation using MOCA and radiofrequency endovenous ablation (RFA) with six months' follow-up. Patients undergoing local anaesthetic endovenous ablation for primary varicose veins were randomised to either MOCA or RFA. Pain scores using Visual Analogue Scale and number scale (0-10) during truncal ablation were recorded. Adjunctive procedures were completed subsequently. Pain after phlebectomy was not assessed. Patients were reviewed at one and six months with clinical scores, quality of life scores and duplex ultrasound assessment of the treated leg. A t...

Phlebology / Venous Forum of the Royal Society of Medicine, Jan 30, 2015

Varicose veins are common and their management has undergone a number of changes over the years. ... more Varicose veins are common and their management has undergone a number of changes over the years. Surgery has been the traditional treatment option, but towards the 21st century, new endovenous thermal ablation techniques, namely, radiofrequency ablation and endovenous laser ablation, were introduced which have revolutionised the way varicose veins are treated. These minimally invasive techniques are associated with earlier return to normal activity and less pain, as well as enabling procedures to be carried out as day cases. They are, however, also known to cause a number of side-effects and involve infiltration of tumescent fluid which can cause discomfort. Non-thermal, non-tumescent methods are believed to be the answer to these unwelcome effects. Ultrasound-guided foam sclerotherapy is one such non-thermal, non-tumescent method and, despite a possible lower occlusion, has been shown to improve the quality of life of patients. The early results of two recently launched non-thermal...

Phlebology / Venous Forum of the Royal Society of Medicine, Jan 1, 2012

Varicose veins are an extremely common condition causing morbidity; however, with current financi... more Varicose veins are an extremely common condition causing morbidity; however, with current financial pressures, treatment of such benign diseases is controversial. Many procedures allow the treatment of varicose veins with minimal cost and extensive literature supporting differing approaches. Here we explore the underlying evidence base for treatment options, the effect on clinical outcome and the cost-benefit economics associated with varicose vein treatment. The method of defining clinical outcome with quality-of-life assessment tools is also investigated to explain concepts of treatment success beyond abolition of reflux.

Journal of Hospital Infection, Jan 1, 2011

Background: Guidelines and protocols assist in the clinical management of patients, helping to ut... more Background: Guidelines and protocols assist in the clinical management of patients, helping to utilise available resources efficiently, however, there is limited documented guidance on surveillance of patients following open arterial surgery. The frequency of clinical follow up, Doppler ultrasound measurements and radiological imaging should all be justified. Here we review the available literature to offer an evidenced based approach to postoperative care. Method: An electronic search was made of Medline and Embase databases through September 2009 revealing over 2300 studies in the initial searches. Following title and abstract screening, the relevant medical literature concerning post-operative surveillance of open vascular procedures was reviewed (300 papers). 42 papers were included in this review. Surveillance recommendations were constructed from the evidence presented. Results and conclusion: Detailed anatomical imaging is available for the technical assessment in the majority of patients' postoperative management; however there is little Level 1 evidence to guide modality or timing. Grades B and C recommendations form the majority of surveillance recommendations. Clinical review remains the mainstay of surveillance following open peripheral arterial surgery. Duplex scanning is the imaging modality of choice when indicated in most instances. Minimal data exists to quantify quality of life or intervention efficacy. ª

ABSTRACT Varicose veins are a common condition, affecting up to a quarter of the UK population. T... more ABSTRACT Varicose veins are a common condition, affecting up to a quarter of the UK population. They have been shown to negatively impact on patients' quality of life and are an important cause of morbidity. The management of varicose veins may be conservative (including lifestyle changes and compression hosiery) or surgical. Operative treatment aims to disconnect the superficial and deep venous systems at the sites of venous incompetence; traditionally saphenofemoral and saphenopopliteal junction ligation with or without stripping were the mainstay of treatment. In the last decade surgical treatment has been moving towards minimally invasive endovascular techniques, including thermal ablation (by means of radiofrequency, laser technology, steam), cryoablation and mechanochemical ablation. These are less invasive than open surgery and may be done under local anaesthesia.This article discusses the epidemiology, diagnosis and management of varicose veins, including the latest endovascular and targeted open surgical techniques such as haemodynamic surgery and variceal ablation.

This work was presented as a poster in the American Venous Forum 25th Annual Meeting; 28 February... more This work was presented as a poster in the American Venous Forum 25th Annual Meeting; 28 February 2013; Phoenix, Arizona, USA. Quality of life (QoL) is an important outcome measure in the treatment for chronic venous disease. The Aberdeen Varicose Vein Questionnaire (AVVQ) and the ChronIc Venous Insufficiency quality of life Questionnaire (CIVIQ-14) are two validated disease-specific QoL questionnaires in current use. The aim of this study is to evaluate the relationship between the AVVQ and the CIVIQ-14 to enable better comparison between studies and to compare these disease-specific QoL tools with generic QoL and clinician-driven tools. Adults attending our institution for management of their varicose veins completed the AVVQ, CIVIQ-14 and EuroQol-5D (EQ-5D). Clinical data, CEAP classification and the Venous Clinical Severity Score (VCSS) were collected. The relationship between the AVVQ and CIVIQ-14 scores was analysed using Spearman's correlation. The AVVQ and CIVIQ-14 scores were also analysed with a generic QoL tool (EQ-5D) and a clinician-driven tool, the VCSS. One hundred patients, mean age 57.5 (44 males; 56 females), participated in the study. The median AVVQ score was 21.9 (range 0-74) and the median CIVIQ-14 score was 30 (range 0-89). A strong correlation was demonstrated between the AVVQ and CIVIQ-14 scores (r = 0.8; p < 0.0001). Strong correlation was maintained for patients with C1-3 disease (r = 0.7; p < 0.0001) and C4-6 disease (r = 0.8; p < 0.0001). The VCSS correlated strongly with the AVVQ and CIVIQ-14 scores (r = 0.7; p < 0.0001 and r = 0.7; p < 0.0001, respectively). Both the AVVQ and CIVIQ-14 scores correlated well with the EQ-5D score (r = -0.5; p < 0.0001 and r = -0.7; p < 0.0001, respectively). This study demonstrates that there is good correlation between two widely used varicose vein specific QoL tools (AVVQ and CIVIQ-14) across the whole spectrum of disease severity. Strong correlation exists between these disease-specific QoL tools and generic and clinician-driven tools. Our findings confirm valid comparisons between studies using either disease-specific QoL tool.

British Journal of Surgery, 2014

Benefit from carotid endarterectomy (CEA) in symptomatic moderate (50-69 per cent) carotid stenos... more Benefit from carotid endarterectomy (CEA) in symptomatic moderate (50-69 per cent) carotid stenosis remains marginal. The Fourth National Clinical Guideline for Stroke recommends use of the risk score from the European Carotid Surgery Trial (ECST) to aid decision-making in symptomatic carotid disease. It is not known whether clinicians are, in fact, influenced by it. Using the ECST risk prediction model, three scenarios of patients with a low (less than 10 per cent), moderate (20-25 per cent) and high (40-45 per cent) 5-year risk of stroke were devised and validated. Invitations to complete an online survey were sent by e-mail to vascular surgeons and stroke physicians, with responses gathered. The questionnaire was then repeated with the addition of the ECST risk score. Two hundred and one completed surveys were analysed (21·5 per cent response rate): 107 by stroke physicians and 94 by vascular surgeons. The high-risk scenario after the introduction of the ECST risk score showed an increased use of CEA (66·7 versus 80·1 per cent; P = 0·009). The low-risk scenario after risk score analysis demonstrated a swing towards best medical therapy (23·4 versus 57·2 per cent; P < 0·001). CEA was preferred in the moderate-risk scenario and this was not altered significantly by introduction of the risk score (71·6 versus 75·6 per cent; P = 0·609). Vascular surgeons exhibited a preference towards CEA compared with stroke physicians in both low- and moderate-risk scenarios (P < 0·001 and P = 0·003 respectively). The addition of a risk score appeared to influence clinicians in their decision-making towards CEA in high-risk patients and towards best medical therapy in low-risk patients.

Stroke, 2013

should not extend reimbursement indications for carotid artery angioplasty/stenting. A potential ... more should not extend reimbursement indications for carotid artery angioplasty/stenting. A potential crisis looms in the United States of America-related to the proposal for the US Center for Medicare and Medicaid Services (CMS) to allow wider indications for government reimbursement for carotid angioplasty/stenting (CAS). We, the undersigned, are writing to advise CMS to reject this proposal based on overwhelming evidence that it would have serious negative health and economic repercussions for the United States of America and any other country that may follow such inappropriate action. The purpose of this message is not to advise on existing CMS policy. Instead, we wish to advise that current Medicare coverage for CAS should not be extended to routine practice management of asymptomatic carotid stenosis or symptomatic carotid stenosis where the patient is considered at 'low/average risk' of complications from carotid endarterectomy (CEA). We understand that, currently, CMS covers the cost of CAS for the indications listed below (the National Coverage Determination [NCD] for Percutaneous Transluminal Angioplasty [PTA] Dec. 2009): i. Concurrent with carotid stent placement when furnished in accordance with the FDA-approved protocols governing Category B Investigational Device Exemption (IDE) clinical trials. ii. Concurrent with the placement of an FDA-approved carotid stent and an FDA-approved or -cleared embolic protection device for an FDA-approved indication when furnished in accordance with FDA-approved protocols governing post-approval studies.

Phlebology: The Journal of Venous Disease, 2014

Endovenous techniques are, at present, the recommended choice for truncal vein treatment. However... more Endovenous techniques are, at present, the recommended choice for truncal vein treatment. However, the thermal techniques require tumescent anaesthesia, which can be uncomfortable during administration. Non-tumescent, non-thermal techniques would, therefore, have potential benefits. This randomised controlled trial is being carried out to compare the degree of pain that patients experience while receiving mechanochemical ablation or radiofrequency ablation. The early results of this randomised controlled trial are reported here. Patients attending for the treatment of primary varicose veins were randomised to receive mechanochemical ablation (ClariVein®) or radiofrequency ablation (Covidien® Venefit™). The most symptomatic limb was randomised. The primary outcome measure was intra-procedural pain using a validated visual analogue scale. The secondary outcome measures were change in quality of life and clinical scores, time to return to normal activities and work as well as the occlusion rate. One-hundred and nineteen patients have been randomised (60 in the mechanochemical ablation group). Baseline characteristics were similar. Maximum pain score was significantly lower in the mechanochemical ablation group (19.3 mm, standard deviation ±19 mm) compared to the radiofrequency ablation group (34.5 mm ± 23 mm; p < 0.001). Average pain score was also significantly lower in the mechanochemical ablation group (13.4 mm ± 16 mm) compared to the radiofrequency ablation group (24.4 mm ± 18 mm; p = 0.001). Sixty-six percent attended follow-up at one month, and the complete or proximal occlusion rates were 92% for both groups. At one month, the clinical and quality of life scores for both groups had similar improvements. Early results show that the mechanochemical ablation is less painful than the radiofrequency ablation procedure. Clinical and quality of life scores were similarly improved at one month. The long-term data including occlusion rates at six months and quality of life scores are being collected.

ABSTRACT Varicose veins are a common condition, affecting up to a quarter of the UK population. T... more ABSTRACT Varicose veins are a common condition, affecting up to a quarter of the UK population. They have been shown to negatively impact on patients' quality of life and are an important cause of morbidity. The management of varicose veins may be conservative (including lifestyle changes and compression hosiery) or surgical. Operative treatment aims to disconnect the superficial and deep venous systems at the sites of venous incompetence; traditionally saphenofemoral and saphenopopliteal junction ligation with or without stripping were the mainstay of treatment. In the last decade surgical treatment has been moving towards minimally invasive endovascular techniques, including thermal ablation (by means of radiofrequency, laser technology, steam), cryoablation and mechanochemical ablation. These are less invasive than open surgery and may be done under local anaesthesia.This article discusses the epidemiology, diagnosis and management of varicose veins, including the latest endovascular and targeted open surgical techniques such as haemodynamic surgery and variceal ablation.

Reviews in Vascular Medicine, 2016

Phlebology / Venous Forum of the Royal Society of Medicine, Jan 24, 2016

Endovenous thermal ablation has revolutionised varicose vein treatment. New non-thermal technique... more Endovenous thermal ablation has revolutionised varicose vein treatment. New non-thermal techniques such as mechanical occlusion chemically assisted endovenous ablation (MOCA) allow treatment of entire trunks with single anaesthetic injections. Previous non-randomised work has shown reduced pain post-operatively with MOCA. This study presents a multi-centre randomised controlled trial assessing the difference in pain during truncal ablation using MOCA and radiofrequency endovenous ablation (RFA) with six months' follow-up. Patients undergoing local anaesthetic endovenous ablation for primary varicose veins were randomised to either MOCA or RFA. Pain scores using Visual Analogue Scale and number scale (0-10) during truncal ablation were recorded. Adjunctive procedures were completed subsequently. Pain after phlebectomy was not assessed. Patients were reviewed at one and six months with clinical scores, quality of life scores and duplex ultrasound assessment of the treated leg. A t...

Phlebology / Venous Forum of the Royal Society of Medicine, Jan 30, 2015

Varicose veins are common and their management has undergone a number of changes over the years. ... more Varicose veins are common and their management has undergone a number of changes over the years. Surgery has been the traditional treatment option, but towards the 21st century, new endovenous thermal ablation techniques, namely, radiofrequency ablation and endovenous laser ablation, were introduced which have revolutionised the way varicose veins are treated. These minimally invasive techniques are associated with earlier return to normal activity and less pain, as well as enabling procedures to be carried out as day cases. They are, however, also known to cause a number of side-effects and involve infiltration of tumescent fluid which can cause discomfort. Non-thermal, non-tumescent methods are believed to be the answer to these unwelcome effects. Ultrasound-guided foam sclerotherapy is one such non-thermal, non-tumescent method and, despite a possible lower occlusion, has been shown to improve the quality of life of patients. The early results of two recently launched non-thermal...

Phlebology / Venous Forum of the Royal Society of Medicine, Jan 1, 2012

Varicose veins are an extremely common condition causing morbidity; however, with current financi... more Varicose veins are an extremely common condition causing morbidity; however, with current financial pressures, treatment of such benign diseases is controversial. Many procedures allow the treatment of varicose veins with minimal cost and extensive literature supporting differing approaches. Here we explore the underlying evidence base for treatment options, the effect on clinical outcome and the cost-benefit economics associated with varicose vein treatment. The method of defining clinical outcome with quality-of-life assessment tools is also investigated to explain concepts of treatment success beyond abolition of reflux.

Journal of Hospital Infection, Jan 1, 2011

Background: Guidelines and protocols assist in the clinical management of patients, helping to ut... more Background: Guidelines and protocols assist in the clinical management of patients, helping to utilise available resources efficiently, however, there is limited documented guidance on surveillance of patients following open arterial surgery. The frequency of clinical follow up, Doppler ultrasound measurements and radiological imaging should all be justified. Here we review the available literature to offer an evidenced based approach to postoperative care. Method: An electronic search was made of Medline and Embase databases through September 2009 revealing over 2300 studies in the initial searches. Following title and abstract screening, the relevant medical literature concerning post-operative surveillance of open vascular procedures was reviewed (300 papers). 42 papers were included in this review. Surveillance recommendations were constructed from the evidence presented. Results and conclusion: Detailed anatomical imaging is available for the technical assessment in the majority of patients' postoperative management; however there is little Level 1 evidence to guide modality or timing. Grades B and C recommendations form the majority of surveillance recommendations. Clinical review remains the mainstay of surveillance following open peripheral arterial surgery. Duplex scanning is the imaging modality of choice when indicated in most instances. Minimal data exists to quantify quality of life or intervention efficacy. ª

ABSTRACT Varicose veins are a common condition, affecting up to a quarter of the UK population. T... more ABSTRACT Varicose veins are a common condition, affecting up to a quarter of the UK population. They have been shown to negatively impact on patients' quality of life and are an important cause of morbidity. The management of varicose veins may be conservative (including lifestyle changes and compression hosiery) or surgical. Operative treatment aims to disconnect the superficial and deep venous systems at the sites of venous incompetence; traditionally saphenofemoral and saphenopopliteal junction ligation with or without stripping were the mainstay of treatment. In the last decade surgical treatment has been moving towards minimally invasive endovascular techniques, including thermal ablation (by means of radiofrequency, laser technology, steam), cryoablation and mechanochemical ablation. These are less invasive than open surgery and may be done under local anaesthesia.This article discusses the epidemiology, diagnosis and management of varicose veins, including the latest endovascular and targeted open surgical techniques such as haemodynamic surgery and variceal ablation.

This work was presented as a poster in the American Venous Forum 25th Annual Meeting; 28 February... more This work was presented as a poster in the American Venous Forum 25th Annual Meeting; 28 February 2013; Phoenix, Arizona, USA. Quality of life (QoL) is an important outcome measure in the treatment for chronic venous disease. The Aberdeen Varicose Vein Questionnaire (AVVQ) and the ChronIc Venous Insufficiency quality of life Questionnaire (CIVIQ-14) are two validated disease-specific QoL questionnaires in current use. The aim of this study is to evaluate the relationship between the AVVQ and the CIVIQ-14 to enable better comparison between studies and to compare these disease-specific QoL tools with generic QoL and clinician-driven tools. Adults attending our institution for management of their varicose veins completed the AVVQ, CIVIQ-14 and EuroQol-5D (EQ-5D). Clinical data, CEAP classification and the Venous Clinical Severity Score (VCSS) were collected. The relationship between the AVVQ and CIVIQ-14 scores was analysed using Spearman's correlation. The AVVQ and CIVIQ-14 scores were also analysed with a generic QoL tool (EQ-5D) and a clinician-driven tool, the VCSS. One hundred patients, mean age 57.5 (44 males; 56 females), participated in the study. The median AVVQ score was 21.9 (range 0-74) and the median CIVIQ-14 score was 30 (range 0-89). A strong correlation was demonstrated between the AVVQ and CIVIQ-14 scores (r = 0.8; p < 0.0001). Strong correlation was maintained for patients with C1-3 disease (r = 0.7; p < 0.0001) and C4-6 disease (r = 0.8; p < 0.0001). The VCSS correlated strongly with the AVVQ and CIVIQ-14 scores (r = 0.7; p < 0.0001 and r = 0.7; p < 0.0001, respectively). Both the AVVQ and CIVIQ-14 scores correlated well with the EQ-5D score (r = -0.5; p < 0.0001 and r = -0.7; p < 0.0001, respectively). This study demonstrates that there is good correlation between two widely used varicose vein specific QoL tools (AVVQ and CIVIQ-14) across the whole spectrum of disease severity. Strong correlation exists between these disease-specific QoL tools and generic and clinician-driven tools. Our findings confirm valid comparisons between studies using either disease-specific QoL tool.

British Journal of Surgery, 2014

Benefit from carotid endarterectomy (CEA) in symptomatic moderate (50-69 per cent) carotid stenos... more Benefit from carotid endarterectomy (CEA) in symptomatic moderate (50-69 per cent) carotid stenosis remains marginal. The Fourth National Clinical Guideline for Stroke recommends use of the risk score from the European Carotid Surgery Trial (ECST) to aid decision-making in symptomatic carotid disease. It is not known whether clinicians are, in fact, influenced by it. Using the ECST risk prediction model, three scenarios of patients with a low (less than 10 per cent), moderate (20-25 per cent) and high (40-45 per cent) 5-year risk of stroke were devised and validated. Invitations to complete an online survey were sent by e-mail to vascular surgeons and stroke physicians, with responses gathered. The questionnaire was then repeated with the addition of the ECST risk score. Two hundred and one completed surveys were analysed (21·5 per cent response rate): 107 by stroke physicians and 94 by vascular surgeons. The high-risk scenario after the introduction of the ECST risk score showed an increased use of CEA (66·7 versus 80·1 per cent; P = 0·009). The low-risk scenario after risk score analysis demonstrated a swing towards best medical therapy (23·4 versus 57·2 per cent; P < 0·001). CEA was preferred in the moderate-risk scenario and this was not altered significantly by introduction of the risk score (71·6 versus 75·6 per cent; P = 0·609). Vascular surgeons exhibited a preference towards CEA compared with stroke physicians in both low- and moderate-risk scenarios (P < 0·001 and P = 0·003 respectively). The addition of a risk score appeared to influence clinicians in their decision-making towards CEA in high-risk patients and towards best medical therapy in low-risk patients.

Stroke, 2013

should not extend reimbursement indications for carotid artery angioplasty/stenting. A potential ... more should not extend reimbursement indications for carotid artery angioplasty/stenting. A potential crisis looms in the United States of America-related to the proposal for the US Center for Medicare and Medicaid Services (CMS) to allow wider indications for government reimbursement for carotid angioplasty/stenting (CAS). We, the undersigned, are writing to advise CMS to reject this proposal based on overwhelming evidence that it would have serious negative health and economic repercussions for the United States of America and any other country that may follow such inappropriate action. The purpose of this message is not to advise on existing CMS policy. Instead, we wish to advise that current Medicare coverage for CAS should not be extended to routine practice management of asymptomatic carotid stenosis or symptomatic carotid stenosis where the patient is considered at 'low/average risk' of complications from carotid endarterectomy (CEA). We understand that, currently, CMS covers the cost of CAS for the indications listed below (the National Coverage Determination [NCD] for Percutaneous Transluminal Angioplasty [PTA] Dec. 2009): i. Concurrent with carotid stent placement when furnished in accordance with the FDA-approved protocols governing Category B Investigational Device Exemption (IDE) clinical trials. ii. Concurrent with the placement of an FDA-approved carotid stent and an FDA-approved or -cleared embolic protection device for an FDA-approved indication when furnished in accordance with FDA-approved protocols governing post-approval studies.