By Professor Ian Olver AM for oncologynews.com.au.
The control of non-communicable diseases is an emerging problem in low and middle- income countries. As their capacities for treating diseases such as cancer increases they will need to develop evidenced-based policy and will develop a clinical trial capability. Many studies may originate in high income countries and partnering with them, although a logical way of increasing trial capability, also raises important ethical and infrastructure issues.
The designation of a middle-income country is based on its per capita gross national income and there are 53 countires classified as lower middle income and 56 upper middle-income countries. Currently the World Bank describes middle income countries as having 5 of the world’s 7 billion people and yet 73% of the world’s poor.
One big difference between countries is how they organise their cancer services.
One big difference between countries is how they organise their cancer services. When the National Institutes of Health in the United States of America first offered grants for clinical research they distinguished between cancer units – which were essentially cancer wards in hospitals, cancer centres – which were stand-alone multispecialty centres with cancer site specific capabilities, and comprehensive cancer centres – which also encompassed prevention, research and teaching. In middle income countries, most of the cancer services are simple cancer units.
In many low and middle-income countries there are no cancer registries to accurately record the extent of cancer or the impact of policy to reduce the cancer burden. Globocan, a web-based resource of cancer epidemiological data contains cancer information for most countries, but in some, like Papua New Guinea, the numbers are estimates based on cancer incidence and mortality in surrounding countries. In those countries without registries there is likely to be a lack of epidemiological expertise.The disparities in middle income countries that compromise research capacity include having patients live remotely from their treatment. This applies to 70% of patients in India. Moreover, 9 of 10 centres are private and not accessible to those from low socioeconomic groups. Many countries lack trained staff. In India the staff/patient ratio is low; Zambia and Kenya lack surgical oncologists and in sub-Saharan Africa there are very few pathologists. In Jordan, currently there is the problem of having added to their own population the need to treat large numbers of medical travellers from war-torn neighbouring countries who are seeking care. If you add to that, lack of essential cancer drugs and limited or no access to radiotherapy, the challenges of treating patients, aside from doing clinical research seems overwhelming.
There are often inadequate opportunities for young potential researchers to find mentors or research leaders in their countries
Added to lack of cancer treatment infrastructure and trained research staff, there are often inadequate opportunities for young potential researchers to find mentors or research leaders in their countries or be educated in research methodology as part of undergraduate or postgraduate curricula. Greater collaboration between academic institutions may facilitate redressing this. Also, there is a lack of clinical trials infrastructure and funding sources for research.
A solution often proposed, and where there are successful examples, is to develop relationships with researchers in high income countries. These can involve both face to face visits and communicating via videoconferencing which is cheap and easy. This can include mentor/mentee relationships and upskilling to the extent that middle income country researchers can participate at least in well-funded international trials such as those supported by the pharmaceutical industry. Subsequently local studies, perhaps investigator initiated, could then occur.
There some serious issues to consider when bringing cancer treatment trials to low and middle-income countries
However, there some serious issues to consider when bringing cancer treatment trials to low and middle-income countries, Firstly, it is important to decide whether the trial question addresses an issue that is important for a middle-income country. Is the tumour type being studied for the middle-income country? It may be relevant to examine questions such as hypofractionation in radiation in a resource poor country, whereas hyperfractionation studies may be nearly impossible to pursue. Adding value to a trial with a health economic analysis which will be important to translate findings into clinical practice may not be possible locally because of a gap in that type of highly specialised expertise.
There may also be cultural beliefs or competing traditional treatments which make accrual to a trial difficult and lack of education can compromise the ability to obtain truly informed consent. There may be poor quality ethical and scientific review of potential trials and inadequate regulatory process covering new drugs, for example.
One of the major challenges is that in middle-income countries participating in a trial maybe the only way that a poor patient can get access to a new cancer drug which makes patients vulnerable. It is easy to exploit patients in that situation, particularly ensuring a balanced education about risk and benefits. There may be poor awareness of patient rights, for example to compensation for trial related injury. This scenario also highlights the necessity for negotiating that a drug remains available to a patient who is responding to it at the conclusion of the trial.
A broader issue is that populations from middle-income countries must share in the benefits of the research with those from higher income country participants. This may mean facilitating access to a successful new drug. It is not always easy to measure what value or burden a research project may have in a developing country.
There are also many positive benefits to pursuing research in middle income countries.
Partnerships with high-income country researchers is a desirable way to upskill those in middle-income countries which enables them to participate in international studies. However, the vulnerability of their potential trial participants and the importance of ensuring the people in the middle income country tangibly benefit from the research is essential.There are also many positive benefits to pursuing research in middle income countries. The clinical trial infrastructure developed in a country may be a lever to increase the quality of the routine treatment delivered. By doing research in middle income countries the industry is getting good value for money and more rapid accrual to trials which can benefit all patients globally.