COMPARATIVE EFFECTIVENESS COMPARATIVE EFFECTIVENESS RESEARCH IN NIGERIA: THE RESEARCH IN NIGERIA: THE

MILESTONES AND THE MILLSTONEMILESTONES AND THE MILLSTONE

A PRESENTATION BYENEMBE OKOKON

BackgroundBackgroundThe import of evidence driven decision

making cannot be overstated, particularly in a resource constrained setting. (Sox et al. 2010)

Ever so often within these climes, multiplicity of healthcare needs outstrip available resources.

The challenge is how to best serve the most compelling needs of the teeming populace by a fair balance of evidence & resource outlay within the imperatives of the socio-cultural context.

Political will is invaluable in this regard.

Background -2Background -2With a pallet of healthcare

interventions aimed toward promoting, protecting, preserving and restoration of health; research output should be streamlined to ‘nuggetwise’ cues providing evidence health planners can use for best outcomes.

DefinitionDefinition“The generation and synthesis of

evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition, or to improve the delivery of care.” (Oxman, 2009)

A succinct definition describes CER as research that generates evidence that compares treatment (USCBO, 2007)

A keyword in this whole concept is ‘effectiveness’ as against ‘efficacy’. While efficacy denotes interventional results in ideal research settings, effectiveness takes cognizance of constraints inherent within the context to which the intervention is applied.

These same constraints may dictate the thrust of native research within such settings.

In a developing country context CER would be a handy tool for the policy process and decision making.

Considerations of sustainability of interventions, evidenced as ideal, for achieving desirable health outcomes should be carried along as worthy objectives of CER studies as well as methods for transmitting research findings to policy frontlines (Sox, 2010; Docteur, 2010).

As earlier implied, though familiar development indices underscore developing countries, peculiarities exist with respect to national priorities, resource base, available technologies and infrastructure, philosophies and cultures, and penchant for adaptation.

Using the Nigerian situation as a gauge within the West African sub-region, this presentation attempts to provide a perspective on the state of CER in a developing country setting.

The approach here will be to examine the priority CER areas; the fundamental questions and issues addressed by such research; and the extent to which such research approximates priorities outlined by policy makers.

A Developing Country A Developing Country ScenarioScenario

As is stated in the Nigerian 2004 Revised National Health Policy document:

“Health Status◦ Preventable diseases account for most of Nigeria’s

disease burden and poverty is a major cause of these problems.

◦ Our maternal mortality rate (about one mother’s death in every one hundred deliveries) is one of the highest in the world.

◦ Some other health indicators, such as under-5 mortality rate, are higher than the average for sub-Saharan Africa ….”

“Health Policy, Legislation, and Health Sector Reform Agenda◦ There is limited capacity for policy/plan/programme

formulation, implementation, monitoring and evaluation at all levels …”

A Developing Country A Developing Country Scenario(2)Scenario(2)“Health Service Delivery and

Quality of Care◦Disease programmes, such as

HIV/AIDS, TB, malaria and other programmes, such as reproductive health, are currently being implemented within a weak system and have had little impact …”

A Developing Country A Developing Country Scenario (3)Scenario (3)“Health Finance

◦Public expenditure on health is less than $8 per capita, compared to the $34 recommended internationally. Private expenditures are estimated to be over 70% of total health expenditure with most of it coming form out-of-pocket expenses in spite of the endemic nature of poverty.

◦There is no broad-based health financing strategy.”

Is There Room for Is There Room for Research???Research???An acknowledgement of the pivotal role of

research in health decision making is made by policy gurus in the 3rd chapter of the same document under the heading, “National Health Planning.”

One bullet point under this heading states that, “The functions inherent in health planning shall be broken into: ◦ (i) Research, that is, analytical and descriptive

processes resulting in strategic policy choices and long-term objectives, will be a continuous process that cannot appropriately be fitted into an annual cycle, though an annual summary of long-term aims and objectives shall be produced as a background to programming decisions …”

Ample Room for ResearchAmple Room for ResearchThe chapter carries these subheadings (which I

estimate to be the priority areas): National Policy on HIV/AIDS National Policy on Roll Back Malaria National Policy on Immunization National Policy on Control of Onchocerciasis National Policy on Control of Tuberculosis and Leprosy National Policy on Blood Transfusion National Policy on Elimination of Female Genital

Mutilation National Policy on Reproductive Health National Policy on Adolescent Health National Policy on Food and nutrition National Policy on Child Health National Policy on Drugs National Policy on Food Hygiene and Safety Practices

METHODOLOGYMETHODOLOGY

This study proceeded as a desk review of journal articles on CER studies conducted in Nigeria.

The included studies were retrieved from PubMed and Cochrane database searches.

PubMed Database SearchPubMed Database Search

The search was done using search syntax constructed with the terms:Compar* , effectiv* , research , study,

NigeriaBoolean operators were used to

connect the terms and the search builder was used to refine searches.

Cochrane Database Cochrane Database SearchSearchThe search was conducted using a full

administrative listing of Nigerian authors. Completed reviews by these authors were scrutinized and appropriate data obtained.

Selection criteria for studies were:1. Study must have been carried out by a

Nigerian author with affiliations to a Nigerian institution.

2. Study design: completed systematic reviews, RCT, CCT or analytical study comparing interventions.

Data ExtractionData Extraction Data was extracted using a simple questionnaire

developed by the reviewer. Key areas of interest were:

The broad classification of disease/conditions informing interventions.

The specific condition being intervened upon. The geopolitical zone within Nigeria where the

investigator(s) is based. The intervention type e.g.diagnostic, preventive

etc. The intervention end-points.

The diseases/conditions investigated in the studies were broadly classified based on the ICD 10th revision. This was modified to accommodate conditions which were not diseases per se. Some interventions simply aimed to promote health.

ResultsResultsThe PubMed search yielded 376 hits

out of which 89 met the inclusion criteria. Use of the search builder yielded no did not alter the results .

Additional search of the Cochrane library (using the list of Nigerian authors) yielded 10 more studies, giving a total of 99 studies.

Studies included included Systematic Reviews(18;18.2%); RCTs (54;54.5%); CCTs (21;21.2%); Analytical Studies(6;6.1%).

Conditions Researched:Conditions Researched:Broad

categorization of researched diseases/conditions showed that infectious/parasitic diseases were the most researched (48.5%), followed by reproductive health conditions (24.2%), and thirdly cardiovascular (CV) conditions (8%).

Fig. 1. Relative Proportion of Infectious Ds./Parasitic Infestations Studied

Of the 48 studies on infectious/parasitic conditions, there were 23 malaria studies which made up 47.9% of total, while HIV/AIDS related studies made up 6.3%.

Fig. 2. Proportion of Female Reproductive Health Conditions Studied Twenty-four research studies were interested in female reproductive health; 10 studies on contraception made up 41.7%; studies aimed at improving conduct of labour were 7(29.2%), and studies on interventions to prevent post-partum haemorrhage contributed 12.5%.

Fig. 3. Proportion of Cardiovascular Conditions Studied

Conditions Researched by Conditions Researched by Geopolitical Zone Geopolitical Zone

ECOWAS, 2008

Conditions Researched by Geopolitical Conditions Researched by Geopolitical Zone (2)Zone (2)

Summary estimates of study interests by region demonstrated that the highest volume (62.6%) of research emanated from the Southwestern zone of the country. Majority (44%) of the Southwestern studies was on Infectious/Parasitic diseases; 29% were on reproductive health interventions; and 8% were on CV interventions. There were 7 Southeastern CER studies which were on Infectious/Parasitic Ds. (28.6%), CV diseases (28.6%) and Reproductive Health conditions (14.3%).

Fig. 4. Broad Categories of Southwestern Studies

There were 13 studies from the South southern zone, 53.8% of these There were 13 studies from the South southern zone, 53.8% of these were on Infectious/Parasitic diseases., and 15.3% were on Reproductive were on Infectious/Parasitic diseases., and 15.3% were on Reproductive health. health. There was only one study (on reproductive health) jointly conducted by There was only one study (on reproductive health) jointly conducted by researchers in from the Southwestern/Southeastern parts of Nigeria.researchers in from the Southwestern/Southeastern parts of Nigeria.

Fig. 5. Broad Categories of Southeastern Studies

Fig. 6. Broad Categories of South southern Studies

Sixty-seven percent of the studies from the North central zone were on Infectious/Parasitic conditions. Most studies from the Northeastern zone focused on the same area. Studies on management of Envenomation (from snake bites) formed 67% of Northwestern articles.

Fig. 8. Broad Categories of North central Studies

Fig. 9. Broad Categories of Northeastern Studies

Fig. 9. Broad Categories of Northeastern Fig. 9. Broad Categories of Northeastern StudiesStudies

Trend in CER in Nigeria over Trend in CER in Nigeria over 35 years35 years

There has been no consistent trend in CER on any of the broad groups of diseases and conditions from 1975 to 2010. Frequency of Infectious Ds. studies waxed and waned with increasing up-thrust from 1989 to 2009, followed by a sharp dip. Reproductive health CER studies show a lower turn-over over time, howbeit with less flux. Occurrence of CER studies for other categories was somewhat sporadic.

Intervention Types & Intervention Types & EndpointsEndpoints

Analysis of the intervention types showed that most, 62%, of the interventions aimed at achieving cure of a condition; 29% aimed towards prevention. There was no rehabilitative intervention.

Most studies (94%) had interest in efficacy of interventions, 60.6% had an adverse effect component among the endpoints. Twelve studies (12.1%) probed into adverse effects, only 6 (6.1%) considered cost, 4 (4.0%) probed into acceptance of intervention by the patient/target population. No study investigated change in quality of life following intervention.

Study Endpoints by Broad Disease Study Endpoints by Broad Disease CategoriesCategories

Interventional endpoints were also explored according to broad categories of conditions and a few specific conditions. Most intervention studies (97.9) on problems of infections and parasites focused on efficacy of intervention, 45.8% addressed adverse effects of intervention and 35.4% addressed treatment failure.

The reproductive health CER studies focused mainly on efficacy The reproductive health CER studies focused mainly on efficacy (95.8%), adverse effects (75%), and treatment failure (41.7%). (95.8%), adverse effects (75%), and treatment failure (41.7%). Only 25% addressed compliance and 12.5% addressed Only 25% addressed compliance and 12.5% addressed acceptance.acceptance.

The cardiovascular studies addressed The cardiovascular studies addressed efficacy (100%), adverse effects efficacy (100%), adverse effects (87.5%) and compliance (12.5%).(87.5%) and compliance (12.5%).

Funding/SupportFunding/Support35% of studies received financial

support.Of these:

◦61% were from foreign sources◦33% were from domestic private sector

sources◦6% were from government

◦29% of all studies received material support mostly from domestic private sector sources.

Discussion - Infections and Discussion - Infections and InfestationsInfestations

The higher proportion of studies in the area of communicable diseases and infections is in keeping with the epidemiological profile of many developing countries where diseases consistent with economic deprivation place a higher burden on the population.

Malaria studies constitute 23% of all articles reviewed in this paper.

The ubiquitous nature of the malaria scourge may well be an incentive for interest.

Infections and Infections and Infestations (2)Infestations (2) It is estimated that the number of

fever/malaria episodes per person per year is 1.5 for children less than 18; months 3.5 for children under 5 years; and 0.5 for children 5 years and older yielding a total of 70-110 million clinical cases per year. (FMOH, 2009; Malaria Consortium, 2008).

The overall malaria mortality rate is 156 per 100,000 (World Statistics, 2009).

Curiously studies on HIV/AIDS are much lower, 3% overall.

Ongoing PEPFAR programme granting scaled up access to free medication (PEPFAR, 2010) not an incentive for HIV/AIDS studies.

Only one study explored tuberculosis.

Reproductive Health & CV Reproductive Health & CV DiseasesDiseasesSome focus on reproductive health is

apparent among these studies. High indices of birth rate

(41/100000), maternal mortality (1100/100000), in contrast to a low contraceptive prevalence of 14.7% well documented (WHO, 2010; NDHS, 2008; PRB, 2009).

Cardiovascular diseases also provide some impetus for comparative intervention studies, with hypertension taking the lead.

Any patterns peculiar to Any patterns peculiar to zones?zones? North/South dichotomy in socioeconomic and

health indices (Malaria Consortium, 2008; NDHS, 2008), do health priorities would vary accordingly?

Every geopolitical zone in Nigeria has several tertiary health facilities with skilled staffs competent to conduct intervention studies.

The highest volume of studies is seen to emanate from the Southwestern zone, and the least from the Northwestern zone. Only one study was jointly conducted in two zones.

The CER pattern is consistent for most geopolitical zones, with infectious/parasitic disease studies showing dominance followed by reproductive health studies.

The Northwestern zone however has a greater share of envenomation studies.

TimetrendsTimetrendsAppraising the trend in CER studies since

1975 … no consistent pattern. From years 1995 to 2009 there is seen a

gradual build up of CER studies on infectious/parasitic diseases only to be succeeded by a deep plunge after 2009.

Most of these studies were on malaria and they may reflect the drive to find reliable drugs to achieve clinical and laboratory cure following the emergence of widespread drug resistance by the malaria parasite.

Going by the overall low volume of studies in this area it’s hard to tell if the pattern seen for infectious/parasitic diseases reveals any true trend.

Intervention Types & Intervention Types & EndpointsEndpoints

Most interventions were directed toward achieving cure. Strong mismatch between the overall numbers of curative

and preventive intervention. A peculiar find in health service delivery in Nigerian is the disproportionate emphasis on curative objectives to the detriment of prevention.

Resource limitations should inform research into viable, effective and efficient methods. This logic does not seem to reflect in the negligiblel number of studies that consider economic evaluation.

Most studies address intervention efficacy, and a higher proportion of studies addressed adverse effects/tolerability. Treatment failure was considered in some studies, and a few considered user/patient compliance with therapy.

Most infectious disease studies addressed efficacy, few considered adverse effects and treatment failure. More malaria studies (60.9%) addressed treatment failure which is in keeping with concerns about drug resistance. A similar scenario is seen with reproductive health studies. Cardiovascular studies emphasized efficacy and adverse effects.

ReferencesReferences

CBO (2007). Research on the Comparative Effectiveness of Medical Treatments: Issues and Options for an Expanded Federal Role. Congress of the United States. 

Docteur E, Berenson R (2010). How Will Comparative Effectiveness Research Affect Quality of Health Care? Timely Analysis of Immediate Health Policy Issues. Urban Institute. 

FMOH (2008). Strategic Health Plan 2009-2013: National Malaria Control Programme. Federal Ministry of Health, Abuja, Nigeria..

FMOH (2005). Revised National Health Policy. Federal Ministry of Health, Abuja, Nigeria. 

Malaria Consortium (2008). Roll Back Malaria: Country Needs Assessment. Nigeria Report. 

National Population Commission (2009). Nigeria Demographic and Health Survey 2008. NPC of the Federal Republic of Nigeria, Abuja, Nigeria. 

Oxman AD, Lavis JN, Fretheim A, Lewin S (2009). Support Tools for Evidence-Informed Health Policy Making (STP) 17: Dealing with Insufficient Research Evidence. Health Research Policy and Systems, 7(Suppl 1):S17

Population Reference Bureau (2009). 2009World Population Datasheet.  Sox HC, Helfand M, Grimshaw J, Dickerson K, Tovey D et al. (2010).

Comparative Effectiveness Research: Challenges for Medical Journals. PLoS Med 7(4): e1000269. doi:10.1371/journal. pmed.1000269 

WHO (2010). World Health Statistics 2010. ISBN 978 92 4 156398 7

THANKS FOR LISTENING