A web-based study concept designed to progress clinical research for ‘orphan’ disease areas in haematological oncology in the elderly: The SHIELD programme

doi:10.1016/j.critrevonc.2006.07.002

Critical Reviews in Oncology/Hematology

Volume 61, Issue 1, January 2007, Pages 79-83

https://doi.org/10.1016/j.critrevonc.2006.07.002 Get rights and content

Abstract

Clinical randomised trials (RCT) in elderly populations with haematological malignant disease are rare and difficult to perform. This paper describes the methodology and process of organising an internet-based international programme for Hodgkin's lymphoma in the >60 years age group in a format which is compliant with the European Clinical Trials Directive (EUCTD). International agreement was obtained on the need for a web-based data collection system for basic registration and evaluation which incorporated an electronic case report system (eCRF) for a Phase II Study. Objective assessments of co-morbidity, activities of daily living (ADL) and instruments of daily living (IADL) were built-in to define objective frailty, linked to physician treatment choice or inclusion on the Study protocol. The programme is now operating effectively in the UK and Germany and provides an organisational model of how research in ‘orphan’ disease areas of haematological and solid tumour oncology, previously considered very difficult, might be overcome.

Introduction

Classical randomised studies are difficult to conduct in a large number of haematological malignant diseases and solid tumour cancers and are even more difficult in the elderly where the >65 years age group accounts for some 60% of patients. In this age group reports suggest that the elderly represent only 22% of patients enrolled in Phase II clinical trials [1]. Utilising the principles learned when conducting population-based registry studies (PACE programme: Population Adjusted Clinical Epidemiology [2], [3]) we have employed the registration approach linked to a Study protocol and made this available on the internet.

It is quite clear that in the cancer portfolio there are a number of ‘orphan’ disease areas which we define as a disease area in which: (a) there is no agreed standard treatment approach; (b) it is impossible or very difficult to investigate in a classical trial format (due to rarity of the disease, advanced age, etc.); (c) there are large numbers of subjects who are unduly frail or have excessive co-morbidity problems; (d) approach to curative treatment is absent or inconsistent.

This report describes the development of the Study of Hodgkin lymphoma In the Elderly/Lymphoma Database (SHIELD) Study programme to provide logical data collection and therapeutic options for a rare but curable cancer in which outcomes have not improved in 15 years [4].

The programme allows individual physicians to register and treat with either the Study protocol or an alternative. Collection of all data gives a method of providing an accurate outcome profile, particularly for the elderly or uncommon disease areas. By linking this to assessment and documentation of co-morbidity [5] and functional scales of daily living (so important in cancer treatment delivery) [6] the results can provide a reality-based programme for evaluation of these disease areas prospectively. Quality of Life assessments (Study patients only) are performed at diagnosis, end of treatment and two years and five years post-diagnosis.

We consider such an approach can be utilised easily for the other areas of difficulty in Hodgkin's lymphoma (HL) including adolescent and relapsed disease as well as other areas of haematology/oncology in older populations

Section snippets

Methods

In a previous background population study of HL >60 years, our group discovered that no improvement in outcome had occurred in HL patients in a 15-year period [4]. The initial approach, therefore, was to the International Hodgkin's Lymphoma Task Force to offer the Newcastle Group as lead for an international effort to improve outcome in this area. Seminars were held at the Cologne Hodgkin's Lymphoma Symposium in September 2001 [7] and this was followed by the convening of representative

Clinical research governance

Due to new legislation and concern about research governance, the regulatory and governance environment for clinical trials in the UK and the other Member States of the European Union changed considerably in 2005. A profound effect was caused by the Directive 2001/20/EC of the European Parliament (EU Clinical Trials Directive: published 4.4.2001). At the time of implementation of the SHIELD programme many Universities and Hospitals in the UK and elsewhere were not yet familiar with issues

A number of European collaborators or national groups were consulted and are now involved

A number of European collaborators or national groups were consulted and are now involved. Further international involvement is sought. Different groups may have different Phase II studies but they are encouraged to enter their patients in the system. The German National Study Group has done this for the BACOPP patients.

Utilising collected tissue and serum, investigations are planned to enable correlation of outcome with biological parameters with the ultimate intent of producing a prognostic

Discussion

At a recent meeting of the International Society of Geriatric Oncology 2005 it was clearly recognised that existing classical RCT approaches were often not applicable or failing to deliver in clinical research terms and could not, as presently constructed, be regarded as the optimal tool for evaluation of cancer in the elderly [1]. The data on the SHIELD programme described here was presented as a method of improving clinical and research evaluation (registration and formal Study combined with

Reviewers

Dr. Dick Johan Van Spronson, UMCN, Medical Oncology 550, P.O. Box 9101, NL-6500 HB Nijmegen, The Netherlands.

Professor Andreas Engert, Hematology & Oncology, University Hospital of Cologne, Department of Internal Medicine I, Kerpener Str. 62, DE-50924 Cologne, Germany.

Dr. Alessandro Levis, Hematology Division, Ospedale SS Antonio e Bagio e C Arrigo, Via Venezia 18, IT-15100 Alessandria, Italy.

Acknowledgements

The research is supported by Marrow and Stem Cell Transplant 2000 (The Millenium Fund), and grateful thanks are due to Dr S.G. O’Brien and PowerTrial Ltd. (www.powertrial.com) for development of the web-based computer systems.

S.J. Proctor, FRCP, FRCPath (Professor of Haematological Oncology, Newcastle University, UK). Professor Proctor is co-founder of the Scotland and Newcastle Lymphoma Group (SNLG) and his main research areas are related to population studies in leukaemia and lymphoma. The laboratory interests of the Newcastle Group are related to bone marrow transplant biology and molecular aspects of minimal residual disease in leukaemia.

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It is perceived by the SHIELD study group that by utilising this regimen results may be enhanced, though differences may be seen in EBV-positive and EBV-negative patients. This also assumes that treatment is reserved for patients who can receive over 80% dose intensity, and those with excessive frailty and co-morbidity are excluded and treated with alternative approaches (Table 1) [30]. The Vancouver group introduced the ODBEP schedule (vincristine, doxorubicin, bleomycin, etoposide, prednisone) for treatment of elderly patient with advanced HL.
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J. Wilkinson, BA Hons. (Study Manager). Mrs Wilkinson is a member of the Newcastle Group's lymphoma research team and has experience in co-ordination of population studies and clinical trials.

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A web-based study concept designed to progress clinical research for ‘orphan’ disease areas in haematological oncology in the elderly: The SHIELD programme

Abstract

Introduction

Section snippets

Methods

Clinical research governance

A number of European collaborators or national groups were consulted and are now involved

Discussion

Reviewers

Acknowledgements

Ann Oncol

Ann Oncol

Ann Oncol

Never too old? Age should not be a barrier to enrolment in cancer clinical trials

Oncologist

Hodgkin's disease: a population- adjusted clinical epidemiology study (PACE) of management at presentation

Q J Med

The PACE (population adjusted clinical epidemiology) strategy: a new approach to multi centred clinical research

Q J Med

Hodgkin's disease in the elderly: a population based study

Br J Haematol