Treatment Program Policy Analysis
program
Egypt’s Viral Hepatitis Program
Treatment Program Policy Analysis
2017
This report is developed as part of the World Bank’s
Technical Assistance on Strengthening Egypt’s Response to
Viral Hepatitis.
Comments and suggestions concerning the report contents are
encouraged and could be sent to emassiah@worldbank.org
2
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3
Table of Contents
Table of figures 6
List of tables 6
Abbreviations 7
Definitions 9
Acknowledgement 10
Overview 11
Executive Summary 12
Introduction 14
Epidemiology 16
i) Global Epidemiology of Viral Hepatitis: 16
ii) Epidemiology in Egypt: 17
iii) Epidemiology of Chronic Hepatitis in Chronic Kidney
Disease patients: 19
CHC Patient Characteristics in Egypt 20
Demographic Characteristics: 21
Infection: 22
Signs and Symptoms (presentation): 23
Healthcare Professionals contact: 23
Diagnostic tools and Diagnosis: 25
Burden of treating CHC patients: 27
Burden of not treating CHC patients: 28
Analysis of Egypt’s Pharmaceutical Market for HCV 29
Overview of the pharmaceutical sector in Egypt 30
Current approach to treatment of viral hepatitis and potential future trends 33
4
Availability and price of hepatitis treatments in Egypt 35
Factors defining access to treatment and treatment outcomes 38
Costing the drug component of a long-term plan to eliminate Hepatitis
C in Egypt 39
Main Findings for the HCV Pharmaceutical Market in Egypt 40
Treatment Journey in the Public Sector 41
Patient steps: 41
Advantages of the NCVVH system: 44
Disadvantages of the NCVVH system: 45
Treatment compliance and stay on therapy: 47
Monitoring and SVR: 48
Treatment Outcomes: 48
Dealing with Relapsers and Non-responders: 49
Re-Infection: 49
Treatment Options in the Private sector 49
Treatment Choice in Private Sector: 51
Treatment Initiation, continuation and Supply in private sector: 52
Sales retail analysis in the private sector: 54
Recommendations 55
Annex I 61
Quantitative perception analysis on CHC treatment Journey
(Hepatologists perspective) 61
Annex II 71
Options to verify the quality of Egyptian generics used in publicly
financed treatment campaigns 71
References 73
5
Table of figures
Figure 1: HCV Prevalence in the Population age 1-59, by Age, Egypt
17
2015 (EDHS)
Figure 2: Phases of HCV from incubation to chronic 20
Figure 3: CHC patient journey 21
List of tables
Table 1: Percentage of HCV patients’ age ranges: 22
Table 2: Percentage HCV patients having the following co-morbid
conditions: 22
Table 3: Percentage of HCV patients referred to physicians’ office
from another physician: 23
Table 4: Source of referral of HCV patients 24
Table 5: No. of days from indicated as HCV till receiving a treatment 24
Table 6: The frequency of the prescribed investigations by doctors 25
Table 7: Relative perception of hepatologists by percent 26
Table 8: Current negotiated prices for one month of HCV treatment
with DAA in EGP 35
Table 9: Treatment costs for the first five years of a Hepatitis C
elimination campaign 39
Table 10: perceived treatment combinations in private sector from
Hepatologists perspective 51
Table 11: Perceptions of physicians on the challenges facing the
patients to receive treatment in the public system 53
6
Abbreviations
CAPMAS Central Agency for Public Mobilization and Statistics
CDC Centers for Disease Control and Prevention
CHAI Clinton Health Access Initiative
CHC Chronic hepatitis C
CS Caesarean section
DAA Direct-acting antiviral agent
DOT Duration of Treatment
EASL European Association for the Study of the Liver
EDHS Egypt Demographic and Health Survey
EVR Early virologic response
GOE Government of Egypt
HBV Hepatitis B virus
HCC Hepatocellular Carcinoma
HCP Healthcare Professionals
HCV Hepatitis C virus
HIO Health Insurance Organization
HIV Human Immunodeficiency Virus
HRQOL Health Related Quality of Life
IDU Intravenous Drug User
IFN Interferon
MOF Ministry of Finance
MOHP Ministry of Health and Population
7
MOIC Ministry of International Cooperation
NCCVH National Committee for the Control of Viral Hepatitis
OOP Out of Pocket
OR Odds Ratio
PAT Parenteral Antischistosomal Therapy
PCR Polymerase chain reaction
PEG-IFN Pegylated Interferon
PVT Private
RBV Ribavirin
RBV Ribavirin
RNA Ribonucleic acid
SOFO Sofosbuvir
SVR Sustained virologic response
8
Definitions
Cirrhosis: progressive scarring of liver tissue that may affect the effectiveness
of chronic hepatitis C treatment. Cirrhosis is typically biopsy-proven in clinical
trials of chronic hepatitis C therapies.
Decompensated cirrhosis: the presence of cirrhosis plus one or more
complications including oesophageal varices, ascites, hepatic encephalopathy,
spontaneous bacterial peritonitis, hepato-renal syndrome, or hepatocellular
carcinoma.
Genotype: a classification of hepatitis C based on genetic material in the RNA
strands of the virus. There are 6 main genotypes, which are further divided into
subtypes in some cases.
Interferon-ineligible: patients in whom interferon therapy is contraindicated
due to such conditions as anaemia, alcohol abuse, advanced or decompensated
cirrhosis, or severe psychiatric disorder.
Interferon-intolerant: patients who discontinue interferon therapy prematurely
due to side effects.
Sustained Virologic Response (SVR): absence of detectable HCV RNA,
measured 12-24 weeks following the completion of treatment.
Relapse: recurrence of detectable viral RNA at some point after achieving an
undetectable HCV viral load during treatment.
9
Acknowledgement
This paper was authored by Amr Elshalakani (Health Specialist) with direct
inputs and support from Andreas Seiter (Global Lead) and Islam Anan
(consultant). We are grateful for the leadership, guidance and encouragement
from Ernest Massiah (Practice Manager for the Middle East, North Africa). We
are also thankful for the operational and leadership support provided by Asad
Alam (World Bank Director for Egypt, Yemen & Djibouti).
We gratefully acknowledge the support received from the incumbent Minister
of Health and Population, His Excellency Dr. Ahmed Emad Rady. This report was
written at their direct request and we greatly valued their continuous support,
input, and leadership.
The content of the four reports series was enriched by discussions with Ministry
of Health and Population (MoHP) leadership and staff, whom we thank for their
time and expertise. These include: i) the honorable Leadership and staff of the
Preventive Sector, MoHP; ii) the honorable members of the national committee
for combating Viral Hepatitis; iii) the team of the Viral Hepatitis Unit, MoHP
and iv) the team of the Loans and Grants Administration (MoHP).
This appreciation is extended to the leadership and staff at the Regional Health
Directorates, especially to the viral hepatitis teams working in the field to combat
the disease.
We thank health experts in Egypt who shared their candid views to help
strengthen the format and recommendations of the paper through multiple
engagements. This includes but is not restricted to a spectrum of academicians,
senior health professionals, policymakers, and representatives of professional
associations.
We appreciate the inputs of our World Bank colleagues: Patrick Osewe (Lead
Health Specialist) for his insightful views, and for his overall support of the
activities culminating in this paper. Very warm thanks go to Mohammed Duban
and Mirna Mehrez who assisted with typesetting of this document, and to Rana
Elgazzaz for doing a meticulous graphics job in a very expedient time frame.
10
Overview
This report provides a comprehensive landscaping of the viral hepatitis treatment
market in Egypt, which in the previous years has been changing dynamically, as
more patients are now enrolled on new treatments. With optimistic goals to treat
as many patients as possible, the country is preparing itself to walk the path of
eliminating Viral Hepatitis.
The report covers the viral hepatitis pharmaceutical and treatment market in
Egypt from many different aspects, beginning with the epidemiology data, and
then moving with the patient journey from the early phases of infection and
presentation till reaching treatment outcomes, moving through the process of
different coverage channels whether governmental, private or out of pocket with
gap analysis of each step and recommendations towards how to reach a reform
plan that we hope will aid in reaching an ultimate goal of complete elimination.
Egypt is currently being perceived as a global leader when it comes to mass
treating its population from the disease. From markedly lowering the prices of
medicines to initiating mass screening and treatment programs, many firsts have
been recorded, and with astonishing results. The report will help to document
those experiences and how they were achieved. This, hopefully, will help guide
other country programs based on what, and what did not, work well in Egypt.
11
Executive Summary
As of 2016, more than 5 million Egyptians were estimated to have CHC,
making the prevalence of CHC in Egypt the highest in the world. The NCVVH,
at the time, identified nearly 1 million patients who were already aware of their
condition, while the remaining patients had yet to be diagnosed. Out of that total
number, 2.5 percent suffer from decompensated cirrhosis and around 30,000 are
on dialysis or have stage 4 CKD. The burden associated with HCV infection in
2013 amounted to $3.19 billion in both direct healthcare costs ($560 million) and
indirect costs of loss of life to premature mortality and cost of disability ($2.63
billion).
Around 60 percent of diagnosed CHC cases are males who were discovered
while asymptomatic during mandatory screenings under various employment or
travel programs. Usually the diagnostic tests requested by HCP are ElISA, PCR,
liver function tests, CBC and ultrasound.
During the era of IFN regimens, which used to cost more than 11,000 USD
per patient, the public sector was the main player responsible for more than 90
percent of CHC patients on treatment. The NCVVH treated 350,000 patients
using IFN, of which 175,000 were non-responders and came back for treatment.
Since the arrival of the DAA’s era, as of mid-2017, 1.2 million patients have been
treated with the new medicines, out of which 900,000 were in the public sector
and the rest were either through out of pocket or through private insurance.
Nowadays the market is moving heavily towards getting treatment through the
public sector, mainly because treatment at the public facilities is nearly free of
charge. Nearly all costs, except for a very minimal user fee of less than 2 USD per
patient, are covered by the public facilities. Many treatment combinations are
used at these facilities, but since 2016 Egypt has shifted to locally manufactured
generic products.
In the private sector, the most common treatment combination is Sofosbuvir +
Daclatasvir ± RBV (Generic), representing 60 percent of prescribed combinations.
Physicians perceive the success rate of the new regimens to be around 95 percent
or more for non-cirrhotic, and around 90 percent for cirrhotic patients. Most
12
often, the treatment is given for a duration of 3 months, except for some resistant
cases where treatment is usually extended to 6 months.
In terms of dollar value, the private sector is expected to cover nearly 45 percent
of the total CHC market vs. 55 percent for other sectors (public and other
governmental). A retail sales analysis at the end of 2016 projected that 900,000
patients would receive treatment across all sectors that year (with 250,000 paying
out of pocket).
For the public sector, patients can seek treatment from either the Ministry
of Health and Population (MOHP) or Health Insurance Organization (HIO),
depending on their insurance coverage. Both require an online registration by
the patient, and usually an appointment is scheduled with a treating doctor on
the same week of registration. NCCVH records have shown that 50 percent of the
registered patients do not show up for the next step, mainly attributable to the
lack of awareness and internet illiteracy. Also, many patients, given the relatively
low cost of treatment in the private sector, have opted to pay out-of-pocket in
the private sector rather than waiting for the bureaucratic processes of the public
sector.
The pharmaceutical industry’s perception of the eradication of the CHC is that
it is feasible if there is more collaboration between the industry and the NCCVH,
in terms of organizing the importation of active pharmaceutical ingredients,
pricing of medicines, and ensuring a consistent ordering policy by the public
sector, so that they are able to meet the needs of the NCCVH. Yet quality control
of locally manufactured generics needs to be of more concern, given the current
low sale prices.
13
Introduction
This report comes among a series of reports undertaken by the World Bank on
the request of the Government of Egypt (GOE) for technical assistance to inform
policies that would strengthen the country’s response to viral Hepatitis C. The
President of Egypt has specifically requested the Bank’s technical assistance
during his bilateral negotiations with the Bank’s President at the latter’s visit to
Egypt in July 2015. Further, the Ministers of Health and Population, International
Cooperation, and the Deputy Minister of Finance all reaffirmed this request
during a health sector mission to the country in October 2015.
The purpose of these reports is to provide technical assistance to the GOE
(Ministry of Health and Population and Ministry of Finance) to strengthen
Egypt’s response to viral Hepatitis. These include a policy analysis of the
treatment program (aim of this work), an assessment of the fiscal impact of
needed interventions, input on technical design of the screening program,
recommendations for strengthening the M&E capacity of the Egyptian Viral
Hepatitis program, and further development of the “Plan of Action for the
Prevention, Care and Treatment of Viral Hepatitis, Egypt 2014-2018”. At the
same time, the work will spearhead and help coordinate efforts undertaken by
other development partners, as well as catalyse the transformation of the currently
fragmented governmental efforts into becoming a single effective program.
This report is critical given the GOE’s prioritization of the issue on its agenda.
Government officials have pledged a swift action on the disease with promises of
marked reduction of prevalence rates within a few years to less than 1 percent of
the population. Further, the President of Egypt has publicly promised to treat at
least 1 million patients by the year 2018, a presidential election year.
Chronic Hepatitis C (CHC) is epidemic in Egypt. Elimination through
prevention, screening and treatment has become a national priority to
policymakers, public health and medical care stakeholders. This report was
developed to provide a better understanding of the pharmaceutical market
dynamics within that set of priorities. Egypt has made certain strides and has
managed to move ahead with an ambitious treatment program, both in the public
and private sectors. This report will shed light, in some detail, on this progress,
as well as provide a descriptive analysis and recommendations on the program.
14
Report Methodology and Time-Frame:
the report was developed in 5 phases:
1. Systematic literature review.
2. Thorough analysis of the public system for treating viral hepatitis at
both the central NCCVH level and the public hospitals/centres and HIO
facilities.
3. Focus group discussions with healthcare professionals (hepatologists)
including members of NCCVH. Interviews were done in an audio-recorded
qualitative and quantitative setting, using semi-structured questionnaire
with transcripts and verbatim analysis. 11 interviews were conducted with
Hepatologists for a duration of 60 minutes each.
4. Focus group discussions with pharmaceutical companies producing
CHC products, both multinational and local manufacturers.
5. Analysis of retail audit data and secondary reports for private markets.
6. Report timetable: The study was conducted between March and
September 2016.
15
Epidemiology
i) Global Epidemiology of Viral Hepatitis:
Hepatitis C viral infection (HCV) is a major global health problem with a
prevalence of about 2.5 percent globally and around 3.5 percent in some regions
such as the Middle East. An estimated 130 million people are currently infected
worldwide. Without treatment, about 85 percent of the infected cases will advance
to chronic infection with HCV, with subsequent cirrhosis, end-stage liver disease
or hepatocellular carcinoma. HCV accounts for about 27 percent of the burden
of cirrhosis and 25 percent of hepatocellular carcinoma globally, resulting in a
major burden of disability and premature death in adults, and significant costs to
affected families and society in healthcare expenditures and loss of productivity.
At present, there is no effective vaccine to prevent the infection. Until 2015, the
standard treatment protocol in Egypt had been limited to a combination therapy
of subcutaneous interferon injection and oral ribavirin, for a regimen of 24 to
72 weeks. This treatment was not only very expensive, especially in a developing
country context with a very large burden of disease, but also characterized by low
adherence to treatment, poor overall effectiveness at about 50 percent cure rate,
and considerable side effects. Recently, the advent of new Direct Antiviral Agents
(DAAs) with simple oral administration, high cure rates and better adherence
rates have made it possible to treat this subtype of hepatitis, albeit at a costly price
initially.
Similarly, Hepatitis B viral infection is the world’s silent killer, with nearly 248
million people infected globally, of which 786,000 die each year. Unlike Hepatitis
C, Hepatitis B has a preventive vaccine of 3 doses available in the markets, and is
increasingly adopted by governments worldwide as a main component of their
compulsory vaccination programs for children.
Transmission of both types of viruses has a lot to share with HIV. While vertical
and childhood transmissions are the mainstay of new infections in sub-Saharan
Africa, iatrogenic causes (unsafe blood transfusion, unsafe injections and
improper infection control practices during medical care provision), and unsafe
sex (especially among men who have sex with men- MSM) are the predominant
16
modes of infection in more developed countries. Progression to end-stage liver
disease from initial infection of both types is long and asymptomatic. The acute
infection, if not resolved, usually progresses to liver cirrhosis, hepatocellular
cancer, and may necessitate liver transplantation—putting huge burdens on
the healthcare systems, financial resources, and workforce productivity of the
affected communities.
ii) Epidemiology in Egypt:
Egypt has the highest HCV infection incidence and prevalence in the world at
about 0.2 percent and 7 percent of its adult population (15-59 years), respectively,
with the latter near 15 percent in some geographic areas. Close to 70 percent of
new infections occur in persons less than 25 years of age. As of 2017, although
more than 1 million Egyptians have been treated with DAAs, nearly 4.5 million
adults are still chronically infected, with an estimated 150,000 new people
infected annually, and about 40,000 dying every year, making Hepatitis C the
third-leading cause of death in Egypt after ischemic heart disease and stroke. The
main reason behind such high incidence and prevalence rates is iatrogenic, owing
to unsafe therapeutic injections of parenteral anti-parasitic drugs with reusable
glass syringes to control the schistosomiasis in the 1960s and 1970s (Figure 1),
and later on, bad infection control practices in public and private health care
FIGURE : HCV PREVALENCE IN THE POPULATION AGE - BY AGE, EGYPT
coupled with suboptimal screening for transfused blood.
facilities, (EDHS)
Figure 1: HCV Prevalence in the Population age 1-59, by Age, Egypt 2015 (EDHS)
Source: EDHS, 2015
17
As a result of recent scientific advances of HCV virology, a new group of Direct-
Acting Antiviral (DAA) drugs has been developed, with significantly shortened
treatment period (down to 12 weeks), ease of administration (oral), fewer side
effects, and much higher effectiveness resulting up to 97 percent cure rate in some
settings, depending on the HCV genotype. The new drugs, such as Sofosbuvir
and Daclatasvir, are often given in combination with ribavirin for best results.
Many other newer molecules belonging to the same family are currently being
licensed around the world, with fewer side-effects, easy administration and less
costs.
In 2015, the MOHP started its own program of treating patients. An online
self-application registry was initiated, to which nearly 1.8 million people applied
as of 2016. Nevertheless, due to availability of funding and availability of locally-
manufactured generic medicines, by the end of 2016 the program had treated
about 800,000 patients. The program is based on medical criteria for selection,
leaving the poor at risk of being crowded out, while those who have health
insurance or have access to the Program for the Treatment at the Expense of
State, a state-financed program for the uninsured, would have better access for
the medicines. Moreover, treatment was being offered at 56 dedicated liver units/
centers around the country by 2016.
The GOE has recently showed political leadership by increasing its commitment
to prevent, contain and treat the HCV epidemic. The presidency went public
with its plan to procure enough medicines to treat 1 million patients with the
new generation of drugs at reasonable prices. It has increased procurement of
favourable negotiated brands and supported cheaper locally manufactured
generics. The MOHP has also allowed various companies to sell their products,
at higher prices, at community pharmacies for patients paying out of pocket,
albeit with tight controls for medical supervision and registration.
Hepatitis B also remains a large problem. Nearly 800,000 Egyptians aged 1-59
years have an active hepatitis B infection as shown in the latest EDHS data (2014)
and CAPMAS (official statistical body) projections. The GOE added Hepatitis B
vaccine to the routine national vaccination program 15 years ago. The 3 doses are
taken at 2, 4 and 6 months of age. This has remarkably reduced the prevalence rates
in the age group 1-14 years to below 0.1 percent. On the other hand, age groups
18
15-59 show a 1.5 percent infection rate. The GOE of Egypt is also targeting high
risk populations with vaccinations, notably the healthcare workers. No national
government sponsored treatment program is available in the country.
iii) Epidemiology of Chronic Hepatitis in Chronic Kidney
Disease patients:
There are more than 2.6 million reported CKD cases in Egypt, of which 2 percent
will suffer ESRD(1) (End Stage Renal Disease), double the global norm (1 percent)
(Kramer 2009). Many of those patients undergo regular dialysis at dialysis
centres all around the country. The sero-conversion rate (of acquiring infection
with Hepatitis C) is high, at 12 percent annually. This is mainly attributed to
the lack of safe infection control practices at those centres, especially within the
public facilities.
As of 2008, there were more than 52,000 ESRD patients in Egypt (Barsoum
2013), 52 percent of whom had HCV. However, actions have since been taken to
reduce this number. According to the latest estimates, the range now has become
30 – 55 percent as a result of:
1. The increasing use of erythropoietin instead of blood transfusions to treat
anaemia associated with ESRD.
2. Better Infection control practices at dialysis units.
3. Dedicating dialysis machines for HCV infected patients separate from
those used by non-HCV patients.
Thus, the number of patients suffering from both ESRD (also known as Stage
5 CKD) and CHC is between 16,000 and 29,000 patients, while Stage 4 CKD
with CHC is calculated to be 2,847 patients (“Chronic Kidney Disease - World
Kidney Day”, 2017). This has put an emphasis on prioritizing patients with ESRD
as among the first cohorts of patients for the National treatment program. It
is worth noting that only a few DAAs are licensed for use with HCV patients
suffering from ESRD, most of which are imported.
(1) Expert opinion: Dr. Mohamed Hany Hafez.
19
CHC Patient Characteristics in Egypt
The following section was developed based on inputs of the professional
hepatologists interviewed during the study (Expert Opinion). As shown in Figure
2, after acquiring an infection, most patients pass through an acute phase lasting
1-2 months during which he or she may not have any symptoms (asymptomatic)
or, in 20-30 percent of cases, may show a transient jaundice. A substantial number
of patients will then undergo spontaneous resolution as the body’s immune system
overcomes the disease. Nevertheless, 50-85 percent of those infected (percentage
varying from different study settings) will enter into a chronic infection phase
within 6 months. This chronic infection may last years, with 20 percent of the
patients developing cirrhosis. Further, hepatocellular carcinoma may develop in
FIGURE : PHASES OF HCV FROM INCUBATION TO CHRONIC
nearly 1-4 percent of those infected.
Figure 2: Phases of HCV from incubation to chronic
Figure 3 illustrates a typical CHC patient journey through many different
diagnostic, treatment and treatment outcome milestones. The latter is usually
categorized into either: (i) cure; (ii) no response; (iii) relapse; or (iv) partial
response.
20
FIGURE : CHC PATIENT JOURNEY
Figure 3: CHC patient journey
Demographic Characteristics:
Although the latest national DHS data find no significant differences between
male and female prevalence in the country, data collected in this study from
patients accessing both public and private entities have shown the following:
■ Six out of ten registered HCV patients are male. This is mainly attributed to:
- Males are more likely to be screened for HCV as a pre-requisite for
employment applications in Egypt. Further, the workforce is predominantly
male, so males are more likely to undergo on-the-job screening administered
by the employer.
- Applying for a working VISA for the Gulf countries includes a mandatory
HCV screening test as one of the requested documents for the VISA
issuance.
- In Upper Egypt, males go to traditional barbershops, a practice that prompts
males to screen themselves more frequently than females in fear of acquiring the
infection.
■ About 88 percent of patients are in the age group of 18-65. (Table 1)
■ Almost half of the patients under physician care reside in urban areas.
■ The most common HCV patient co-morbidities as reported by treating doctors
were diabetes (almost 30 percent) and other non-communicable diseases (Table
21
2). Patients with a history of having Schistosomiasis constituted almost one third
of CHC patients.
Table 1: Percentage of HCV patients’ age ranges:
# Age Ranges Percent HCV Patients
1 0-17 1%
2 18-45 43%
3 46-65 45%
4 65+ 10%
Table 2: Percentage HCV patients having the following co-morbid conditions:
# Co-morbid Conditions % of HCV patients
with…
1 HIV positive 0%
2 Hepatitis B 7%
3 Cardiovascular Disease 14%
4 ESRD Disease (patients on Dialysis or Stage 4 CKD) 3%
5 Psychiatric Disorders (i.e. Depression, etc.) 6%
6 Diabetes 29%
7 Other co-morbidities (HTN, Obesity, and Anemia) 23%
8 None 42%
Infection:
Physicians have stated that many CHC patients reported a history of exposure to the
following: (i) blood transfusion; (ii) attending clinics with suboptimal level of sanitation; and
(iii) sharing personal shaving devices. Further, a substantial number of patients were either
related to or are members of the same family, suggesting the sharing of unhygienic habits.
22
Signs and Symptoms (presentation):
Patients usually present asymptomatically due to accidental discovery of the
virus when they undergo testing for various reasons as stated earlier. However,
some do present with symptoms like fatigue, ascites and/or encephalopathy.
Sometimes, the first signs are abnormal lab results such as elevated liver enzymes
or ultrasound examination showing fatty liver.
Healthcare Professionals contact:
The first health provider contact for symptomatic cases will usually be a GP
doctor, pharmacist or nurse. However once the diagnosis has been confirmed,
patients tend to seek hepatologists in their public or private practices via the
multiple and fragmented financial coverage mechanisms available in the country.
In the private sector, nearly 63 percent of hepatologists report diagnosing patients
with CHC for the first time themselves. However 37 percent are referred from
other doctors with a diagnosis already (Table 3).
Table 3: Percentage of HCV patients referred to physicians’ office from another
physician:
# Source Percent HCV Patients
Referred-in from another physician with
1 37%
an HCV diagnosis
2 Diagnosed with HCV by Physician 63%
Of the Hepatitis C patients who are referred, 79 percent are referred from a
private clinic, the rest from the public sector. This indicates that the majority of
patients have a tendency to seek multiple consultations regarding their condition
(Table 4).
23
Table 4: Source of referral of HCV patients
Percent HCV Patients
# Source
Referred From…
1 Public sector 21%
2 Private sector 79%
3 Other (Specify) ______________________ 0%
Among patients attending private clinics, the sources of coverage for
pharmaceuticals needed for treatment varied. Only 38 percent opted to buy it
out of pocket, while more than half obtained them through the public domain,
despite the long delay in waiting lists (Table 5).
Table 5: No. of days from indicated as HCV till receiving a treatment
No. of days from
Percent of
# Source indicated as HCV till
patients
receiving a treatment
1 Health Insurance 22% 157 Days
2 MOHP state coverage program 32% 205 Days
3 Private Insurance 3% 13 Days
4 Companies / big accounts 2% 1 Day
5 Military / Police 1% 21 Days
6 Out of Pocket / Self-Pay 38% 1 Day
7 OOP (Subsidized value of brand) 2% 1 Day
24
Diagnostic tools and Diagnosis:
The following diagnostic workups were mainly used for the majority of patients,
with variable frequency (Table 6):
■ Rapid screening tests (with relatively low sensitivity and even lower
specificity rates)
■ PCR and viral load
■ HCV ElISA (3rd generation)
■ Liver Function (ALT – AST)
■ Renal Function test
■ CBC
■ Ultrasound (to estimate cirrhosis level)
■ Liver biopsy (very few)
Table 6: The frequency of the prescribed investigations by doctors
Percent of Patients Tested
# Test Conducted
for HCV Using…
1 Liver Function Tests (ALT/AST) 100%
2 Viral load / Quantitative HCV test 90%
3 Qualitative HCV test 0%
4 Genotype Test 1%
5 Liver Biopsy 0%
6 Ultrasound 70%
7 Other (Fibroscan, CBC, ELIZA, PCR) 60%
Laboratory testing is perceived by hepatologists as reliable and relatively cheap
in Egypt. The full aforementioned package could cost the equivalent of 56 USD
in private sector laboratories but is free for patients seeking care in the public
facilities and centres. However, some patients may opt for testing in the private
laboratories, provided they can afford it, to avoid long waiting times in the public
domain. Some patients may refrain altogether from doing the confirmatory lab
tests for one or more of the following reasons:
25
■ Asymptomatic patients may not believe HCV is a serious disease, as they are
not suffering, and they may have friends and relatives who have been diagnosed
with CHC for decades with no immediate health concerns.
■ Some patients are afraid to be diagnosed with CHC and begin a treatment
journey that might bear serious consequences in terms of side-effects, financial
burden or psychological stress.
■ Some patients cannot afford diagnostic tests it the private sector yet are
reluctant to seek them in the public facilities owing to the time consuming and
bureaucratic procedures.
Table 7 illustrates hepatologists’ perceptions of the status of HCV patients
visiting to their clinics.
Table 7: relative perception of hepatologists by percent
Percent HCV
# Type of visit
Patients
Therapy Naïve (diagnosed patients that have never
1 26%
been treated and may be treated in the future)
Currently Treated (diagnosed patients that you are
2 41%
currently treating)
Successfully completed therapy (previously treated with
3 30%
HCV therapy successfully, sustained viral response (SVR))
Relapsed from therapy (previously treated with HCV
therapy successfully, but had un-sustained viral
4 3%
response 24 weeks after completion of therapy and who
are not currently receiving treatment)
IFN Treatment Non-responder (previously treated with
HCV therapy unsuccessfully, little or no viral response
5 0%
during therapy and who are not currently receiving
treatment)
6 Discontinued therapy for reasons other than efficacy 1%
26
Burden of treating CHC patients:
Although the World Bank is completing an assessment of the economic burden
of the disease in a separate study, prior evidence has showed mixed economic
estimates. In a study by Waked (2014), the total economic burden of HCV in
Egypt was calculated in 2013 to be around 80 million USD and projected till
2030 from year 2013 based on 2013 current figures to be 3.2 Billion USD or 1.4
percent of GDP. Direct healthcare costs were calculated to be 560 million USD
and indirect costs of loss of life due to premature mortality and cost of disability
2.63 Billion USD (Waked et al., 2014)
In that study, investigators forecasted the future costs based on different
scenarios. In one of the scenarios, in which the success rate of treatments reached
90 percent (below the success rates of 97 percent announced by the government
and NCVVH in 2016), the result was 32 percent fewer viremic individuals in
2030 compared to the 2013, and total costs declining by 30 percent to 2.42 Billion
USD. Direct costs in 2030 were estimated at 363 million USD, a decrease of 35
percent from 2013. Indirect costs were estimated at 1.88 billion USD, a 30 percent
decrease compared to 2013, assuming 65,000 patients were treated annually.
These numbers are clearly outdated, as treatment numbers in 2015 and 2016
significantly exceeded these predictions.
In a study just completed by the World Bank (Haacker 2016), multiple treatment
and screening scenarios were modelled using the most up-to-date information on
costs of treatment and screening in Egypt, as well as data on the prevalence and
incidence of the disease. These studies, described in more detail in that report,
included a demand-driven “treatment scenario,” in which patients voluntarily
seek out treatment; a “screening scenario,” in which the government implements
a screening program to screen 10 percent of all Egyptian adults every year and
treat those who screen positive; and an “elimination” scenario, in which screening
is rapidly scaled up so as to cover essentially the entire population over the next
5-6 years.
Under the “treatment” scenario in that study, deaths from Hepatitis C and the
number of new infections are expected to decline by about one-half by 2030.
Screening (as modelled under the “screening” and “elimination” scenarios)
would significantly augment these effects, averting up to two-thirds of deaths
27
and reducing new infections by around 90 percent in the elimination scenario.
In terms of direct healthcare costs, the “treatment scenario” would be refinanced
by savings in costs of within 6 years, whereas screening and elimination would
require greater spending in the short-run (elimination even more so than
screening), but they are considered cost-effective by conventional norms, and
both approaches are much more effective at finding and treating infected patients
than the treatment approach alone. For more details on the relative costs and
impacts of these policies, please see the full report.
Burden of not treating CHC patients:
Chronic HCV should be analysed as a multifaceted systemic disease leading to
heavy direct and indirect costs. The effects of HCV on the liver and the rest of the
body significantly increase its potential burden, making treatment crucial from a
therapeutic and preventative point of view (Cacoub et al., 2014). Complications
include:
1. Liver related complications
a. Cirrhosis: Approximately, 20 percent of people infected with Hepatitis C
will develop cirrhosis if not treated (HCV Epidemiology in the United States,
2017). In 2010, 24.8 percent of HCV-infected patients were reported to have
already progressed to cirrhosis (Deuffic-Burban, 2010).
b. Hepatocellular Cancer (HCC): Hepatitis C-associated liver disease is the
number one cause of HCC, accounting for approximately 50 percent of cases.
In a study conducted in Menoufia in 2013, HCV infection was present in 91
percent of the HCC cases (Shaker et al., 2013). The cost paid by the general
budget for HCC treatment per patient per year varies from 2,000 to 12,000
EGP, according to the stage of the cancer.
c. Liver Transplantation: Hepatitis C-associated liver disease is the number
one indication for liver transplantation and approximately one-third of all
people on liver transplantation waiting lists have hepatitis C-associated liver
disease. The MOHP contributes 75,000 EGP for transplants; however, the
actual overall cost may reach up to 250,000 EGP. An additional 70,000 EGP
are also paid for post-transplantation medications.
28
2. Extra-hepatic complications
Extrahepatic manifestations have been reported in up to 74 percent of HCV
patients, including:
a. Autoimmune Disorders: Referred to as extrahepatic manifestations
(EHMs), these affect 40 – 70 percent of patients with HCV. Mixed
Cryoglobulinemia (MCG) is the most common, affecting up to 50 percent of
chronic hepatitis C patients (Al Kafrawy et al., 2014).
b. Peripheral Neuropathy: Patients with chronic HCV infection have a high
incidence of developing peripheral neuropathy (from 30 to 45 percent).14
Besides the additional costs of complications from untreated HCV, CKD
patients with untreated HCV pose particular concerns. According to expert
opinion, these individuals may infect 4-5 new people within their community
in their life time (mainly within their own family).
Analysis of Egypt’s Pharmaceutical Market for HCV
With the discovery and development of a new category of drugs against
Hepatitis C known as Direct Acting Antivirals, or DAAs, treatment has become
shorter, better tolerated, and more successful, with cure rates close to 100 percent
for patients in the early stages of the disease.
The latest generation of DAAs against Hepatitis C includes molecules such as
Sofosbuvir, Ledipasvir, Daclatasvir, Grazoprevir, Elbasvir, Velpatasvir, Ravidasvir,
used in combination with each other or with older antivirals such as Ribavirin.
According to current data, the combination of Sofosbuvir with Daclatasvir has
the best overall spectrum of efficacy against all six genotypes of the Hepatitis C
virus. Sofosbuvir plus Ledipasvir is an alternative and may be equally effective
against the genotype 4, which is dominant in Egypt.
In contrast to the early years of HIV/AIDS, in which antiretroviral (ARV)
drugs were very costly and hard to obtain in low and middle-income countries,
originator companies making the DAAs decided early on to provide licenses to
generic manufacturers to make and sell these products in developing country
markets. Had they not, the high prices charged in developed markets would have
blocked access for most Egyptians. This approach has led to a rapid development
29
of several generic alternatives, led by companies in India and Egypt. There is now
growing availability of low price generics in national and international markets,
and several of the larger Indian manufacturers and one Egyptian manufacturer
have initiated the WHO Prequalification process. The first WHO Prequalified
generic Sofosbuvir will soon become available. The same organizations and
international experts that helped to make ARVs for HIV/AIDS affordable are
now working with producers of the active pharmaceutical ingredient (API) and
with generic manufacturers of finished forms. This will ensure a supply of quality,
low cost DAAs for Hepatitis C and allow countries with a high disease burden,
such as Egypt, to plan and afford mass treatment campaigns at a scale that makes
effective control or elimination of the disease a possibility (Dowdle & Cochi,
2011).
The work of international experts at WHO, CDC, CHAI and others has created
a transparent market environment in which it is possible to benchmark prices for
generic DAAs and develop sourcing strategies. Data from these sources are being
used in this analysis. As the market changes constantly with the arrival of new
molecules, introduction of additional generics, growing demand, and technical
progress that may result in cheaper raw materials, today’s data may need to be
reviewed and updated at least in yearly intervals.
Overview of the pharmaceutical sector in Egypt
The pharmaceutical sector in Egypt is regulated by the Egyptian Drug Authority
(EDA), which is part of the MOHP. EDA has three sub-units:
■ CAPA – Central Administration of Pharmaceutical Affairs - for core functions
such as licensing of pharmaceutical products (also food products and medical
devices, but not biologicals), professional licensing, inspection and supervision
of the sector.
■ NODCAR – the National Organization for Drug Control and Research,
responsible for quality assurance of the CAPA regulated products and home of
the drug quality control lab.
■ NORCB – the National Organization for Research and Control of Biologics,
which assumes a range of functions for the regulation and quality control of
biologics and blood products.
30
A new law is currently in preparation that foresees a spin-off of the regulatory
body to give it a more autonomous status. It also envisions a separation of
responsibilities so that the new EDA would only deal with medicines and
medical devices. According to the draft, the new EDA would report to the
president, thereby eliminating the current potential for conflict of interest if the
same ministry that regulates the industry is also the single largest buyer and price
regulator.
Another legislative initiative (Decree 425) aims at speeding up the registration
process for new medicines by creating parallel pathways in the review process
and introducing a Common Technical Document (CTD) format according
to international standards. The goal is to shorten the typical time frame from
submission to issuance of the marketing license from 4 years or more to 18-24
months.
Egypt has a vibrant pharmaceutical industry. There are about 130 manufacturing
plants, some of which make brand name medicines for multinational companies
(the industry association). The domestic industry supplies 90 percent of the
volume of generic drugs consumed in Egypt (or about 60 percent of the value, as
domestic generics are sold at lower prices than international benchmarks).
Fifteen companies so far have obtained a manufacturing license for Sofosbuvir,
10 to 12 are already producing, and 6 are listed as suppliers in the recent public
tender. This tender guarantees a minimum volume of 250,000 packs (one month
supply per pack). According to MOHP, the volume will be split evenly among the
winning companies. The number of manufacturers for Daclatasvir is smaller (so
far 6) but growing.
The Egyptian Drug Authority is not yet internationally recognized as a “stringent”
regulatory authority. Egypt is not member of the PIC/S scheme (“PIC/S”, 2017),
meaning certificates for Good Manufacturing Practices issued by EDA would not
be recognized in other countries. This points towards a risk of quality variation
in the Egyptian market. Companies that are forced to sell at low prices may “cut
corners”, use lower quality ingredients or find other ways to protect their bottom
line unless there is a strong regulator with sufficient enforcement powers and
capacity (see above discussion of conflict of interest if the same agency acts as
regulator and purchaser).
31
The size of the pharmaceutical market in Egypt is about 33 billion EGP(2)
(2015 data, about 4.3 billion US$) (Egypt Pharmaceuticals & Healthcare Report,
2017). This equals about 29 percent of total health expenditures or US$ 52 per
capita consumption of medicines. Egypt is characterized as a country in which
pharmacies are widespread and all medicines can be purchased over the counter
without prescription, or even delivered to the home of the patient, making self-
medication the typical first step in care. The retail sector is large but shows signs
of consolidation with the emergence of pharmacy chains offering lower prices
and a higher degree of professional standards than individual pharmacy shops.
The official retail margin is 20 percent, but pharmacists find ways to buy from
informal channels that offer high volume medicines at discounted prices, thereby
increasing their profit margin. On the other hand, these informal distribution
channels provide an entry point for fake or unlicensed medicines. The MOHP
is developing a track-and-trace system that will become mandatory for all
pharmaceutical businesses in order to address this challenge. Current plans are
to roll this system out over the next three years.
Egypt applies a reference pricing system, controlled by the MOHP, which is
currently being revised (Decree 499). Multinational companies are reluctant
to offer prices that could impact price levels in other countries; therefore, they
sometimes provide hidden rebates in form of free medicines to protect market
share. As about 75 percent of the market is in the private sector and paid for out-of-
pocket, brand preference plays an important role. Reportedly, there are disputes
between physicians and pharmacists professional organizations (syndicates)
as to who gets to define which brand is dispensed (prescribing brand name or
generic name). The underlying issue may be financial: who gets to benefit from
the incentives provided by the industry.
Egypt is planning the introduction of a new social health insurance scheme,
which would replace the current Health Insurance Organization and may offer
an opportunity to bring more discipline into the market, assuming it has enough
resources to be a major purchaser of medicines.
(2) public sector expenditures may not be fully captured in these data.
32
Current approach to treatment of viral hepatitis and potential
future trends
Treatment programs for Hepatitis C have existed for years, but the cost of
interferon and the long duration of treatment have been limiting factors for the
number of patients benefiting from the program. Since DAAs became available,
the country moved quickly to scale up treatment in collaboration with various
stakeholders working together in the National Committee for the Control of
Viral Hepatitis (established 2006). A new strategy document was developed for
the period of 2014 to 2018, covering a comprehensive set of actions to control the
epidemic; treatment is but one of several pillars in the new strategy. Preventing
new infections is obviously more cost-effective and will accelerate the elimination
of the virus reservoir and reduce long term treatment costs.
The roles for defining treatment protocols, setting up treatment centers,
procuring medicines and enrolling patients are defined. The number of treatment
centers has been scaled up – as of 2016, the National Committee counted 56
centers and had plans to open up to 100 centers. HIO has 37 centers and 90
dispensaries at which patients can refill their prescription.
A web based enrollment tool has been launched and 1.8 million Egyptians
registered for treatment. Once registered, they receive a list of lab tests required
for their first appointment and instructions for payment (patient copayment is
EGP 20, about US$ 2.50, which finances the administration costs and overtime
payment for the treatment center staff; physicians and nurses volunteer their
time). They also get an appointment at the treatment center and a list of lab tests
needed to confirm the diagnosis and status of disease. As this procedure can be
challenging for illiterate people or those without internet access, enrollment is
also possible at treatment centers. Internet cafes offer assistance to people who
otherwise do not have access. Although waiting lists for appointments have
largely resolved, temporary drug shortages have delayed treatment for some
patients, although the delays are said to be no more than one month (HIO).
According to NCCVH estimates, at least 800,000 patients received treatment
in 2016 (after 200,000 in 2015), which is in line with the target number needed
to reduce Hepatitis C prevalence to under 1 percent in 2030. Included are about
100,000 patients treated in HIO facilities. The total does not include those
33
treated in the private sector (estimated at 200,000 for 2016), where there is no
mandatory registration or follow up. A system to register patients and refill drug
prescriptions only if patients returned the originally dispensed bottle empty(3)
was in place when treatment relied on the discounted originator drugs, but has
since been abandoned.
Currently, only 50 percent of patients show up for the final lab test scheduled
one month after the end of treatment, which is needed to confirm complete
clearance of the virus or “sustained response”. This lack of follow up is a problem,
as calculating the cure rate for the current treatments will be difficult if patients
do not get the final test.
Fragmentation of the treatment efforts is an issue. MOHP treatment centers,
university hospitals, NGOs and facilities under the HIO each offer treatment
centers but not all of them feed into a single monitoring system. The private
sector also offers diagnosis and treatment in many facilities, some of which are
of low standards and may use substandard lab reagents or medicines. This can
negatively impact cure rates and lead to resistance development against the first
line medicines that are now available at low cost.
(3) The main purpose was to prevent patients from selling Sofosbuvir (initially provided by Gilead, at a
price of about 1% of the official US price) outside the countries in non-discounted markets.
34
Availability and price of hepatitis treatments in Egypt
Six companies have an agreement as suppliers to the MOHP and all other
buying organizations included in the MOHP tender, offering the lowest price for
the public sector and a higher, but still competitive, price for the private sector;
all companies are supposed to sell at more or less the same price (see table 8).
Table 8: Current negotiated prices for HCV treatment with Direct-Acting Antiviral
Drugs (DAA) in US Dollars
Sofosbuvir + Daclatasvir price
Course and Date
in EGP
Full treatment costs (3 months) in public
US$200
sector, 2016
Full treatment costs in public sector since
US$98
2017
These prices are already at or below the hypothetical lowest price that has been
estimated by international experts working for WHO, Clinton Foundation and
USAID. The experts used the experience from the HIV antiretroviral market,
taking into consideration the costs of raw materials (API from Indian and
Chinese sources), costs of manufacturing at scale in a GMP compliant facility
and a reasonable profit margin that encourages a sufficient number of companies
to enter and stay in the market. They arrived at a current theoretical “best price”
of US$ 233 for a full course of combination treatment of WHO Prequalified
Sofosbuvir plus Daclatasvir (USAID, Clinton Foundation and WHO AMDS).
Estimating manufacturing costs and profitability is not an exact science – there
are assumptions to be made and parameters can change rapidly based on scale
and costs of inputs. The fact that Egyptian manufacturers offer such low prices to
their government can have several potential explanations:
■ Companies may have lower manufacturing costs as they do not have the
same sophisticated quality assurance mechanisms that are required for WHO
Prequalification (WHO - Prequalification of Medicines Program) (see explanation
below). However, this is not likely to be the case for one local company, which is
35
the current leader in the Egyptian generic DAA market. This company already
applied for WHO PQ and is in the review process.
■ Companies accept low profit or even losses in the public sector based on
political pressure, some form of material or political compensation in another
area of interest not related to Hepatitis drugs, or in an attempt to build market
share, hoping that this approach leads to higher private sector sales.
These findings raise the question of whether the low prices in Egypt are
sustainable once international quality standards are applied. Current private
sector retail prices for Sofosbuvir in India are higher than the prices negotiated
for Egypt. As of 2016, they ranged from US$ 160 to 320 for one month supply of
Sofosbuvir, compared to approximately US$ 122 for Egypt at the time cost data
was collected.
Considering payment delays that need to be financed and exchange rate
deterioration versus the US dollar, the current prices charged by Egyptian
manufacturers to the MOHP are already below the international benchmark and
not likely to go further down in the near term. Of course, over time API prices
may change, international competition may drive prices down further and the
Egyptian government may want to take steps to take advantage of these possible
market developments by re-negotiating or inviting competition from outside the
country.
As stated above, the price comparison data do not take into account whether
manufacturers have WHO Prequalification (WHO PQ) for their product.
WHO PQ is a prerequisite for participation in many international tenders,
assuming that there are enough manufacturers meeting this requirement. For
the Egyptian government and the local industry, the goal should be to ensure all
Egyptian manufacturers go through this process. This would not only reassure
the government that the medicines used in Egypt to treat the HCV infected
population are of good quality and fully effective, it would also help the Egyptian
industry to be competitive in export markets. For companies that are already
manufacturing at a high-quality standard (Good Manufacturing Practices), the
investment needed for achieving WHO PQ is limited. So far, Pharco has initiated
the process, as have several Indian manufacturers.
Not much is known yet about alternative treatment combinations, for example
36
Sofosbuvir plus Ravidasvir, a new DAA licensed and under development by
Pharco. Early clinical data look promising, but to decide which combination(s)
to pick for mass treatment campaigns, the MOHP would need to apply a “health
technology assessment (HTA)” procedure to identify the cost-benefit ratio and
allocate funds based on best value for money. It is likely that parameters such as
price and treatment outcome data will change over time, which means the review
and decision making process needs to be institutionalized and given sufficient
resources to stay on top of the evolving scientific and market data.
One likely unintended consequence of the difference between public and
private price is that the industry has an incentive to focus marketing activities on
the private sector, potentially pulling ahead of the public sector in screening and
identifying patients who then would pay out of pocket for their treatment. At the
current price level, many patients would probably prefer the less bureaucratic,
pay-as-you-go option over formal enrollment in a public treatment center. If this
turns out to be true, these patients would be lost for the monitoring and disease
surveillance efforts, as the private sector does not yet have an enrollment and
follow-up system.
Developing such a system in collaboration with industry, pharmacists and
privately practicing physicians should have high priority. While technically
relatively straightforward (a public sector system exists already), it may require
monetary incentives to ensure compliance of providers. It should also be easy on
the patient and not add any inconvenience, while providing reminders for refills
and necessary tests. Such a system should be in the interest of manufacturers,
prescribers and pharmacists as it helps ensure patient compliance and thereby
secures future sales.
37
Factors defining access to treatment and treatment outcomes
Thanks to the internet registration portal, the treatment program has reached
literate patients who are aware of—or at least suspicious of—their HCV-positive
status. However, this group may be only 10 or 20 percent of all patients in need
of treatment. The prevalence of Hepatitis C among the poor and uneducated
is moderately higher than among the educated. Screening programs, active
outreach and use of community outreach strategies for enrollment will be needed
to ensure that the treatment program is “fed” with new patients. Monitoring
of patients needs to be improved through a single system rolled out across all
providers offering treatment. Such a system could be based on a mobile platform
and linked to incentives such as free call phone minutes or data. Currently, the
program is offering patients a final “certificate of successful treatment” when they
show up for their final test and are confirmed for “sustained response.” Having
a unified strategy across all treatment platforms (modeled after the “Three
Ones Principles” that has been the basis of success for HIV/AIDS treatment
campaigns(4)) increases the effectiveness and efficiency of all communications
and outreach measures (UNAIDS 2004).
(4) One strategic framework, one coordinating body and one monitoring and evaluation system.
38
Costing the drug component of a long-term plan to eliminate
Hepatitis C in Egypt
Based on current prices and assumptions of patient treatment numbers, the
total costs of the drug component for a treatment campaign can be calculated.
The calculation is provided here for the next five years only. Two scenarios are
shown below: One column reflects the projected drug costs under the “treatment
scenario” in the sister report by Haacker 2016, whereas the adjacent column
reflects drug costs under the “elimination scenario” in the same report. Note
that the drug costs under the elimination scenario are significantly higher as
the screening component of that scenario draws significantly more patients into
treatment and therefore increases spending on medications, at least in the short-
term.
Table 9: Projected Treatment costs (drug costs* only) for the next five years of a
Hepatitis C elimination campaign
Treatment Scenario Drug Elimination Scenario Drug
Year
Costs (US$) Costs (US$)
2017 33.9 million 70.5 million
2018 30.3 million 96.4 million
2019 27.2 million 85.5 million
2020 24.4 million 76.7 million
2021 22.0 million 75.6 million
*Prices reflect non-discounted costs
Depending on the number of patients seeking treatment in the private sector and
paying out of pocket, the public expenditure burden may be lower for achieving
the target treatment numbers. So far, there are not enough data to calculate how
many patients would seek treatment outside the public and HIO centers. The
industry will have access to such data and it should be possible over time to come
up with a good estimate of the out-of-pocket market, which then can be used to
adjust the public expenditure forecast and budget for the treatment provided to
patients for free.
39
Costs for purchasing medicines are only one element of treatment costs, although
probably the dominant one. Future treatment costs can be reduced by investing
in prevention now – every infection avoided saves not only a future treatment,
but also costs for diagnostic tests and evaluations and for lost productivity due to
absence, discrimination and illness.
Treatment campaigns require investment into screening and treatment capacity,
outreach and patient information, systems for management, monitoring and
evaluation and second line interventions for patients that fail to fully respond
to first line treatment. These costs will be covered in other components of the
Technical Assistance project.
Main Findings for the HCV Pharmaceutical Market in Egypt
With the availability of new, effective treatment options for Hepatitis C, Egypt
is in a position to offer treatment on a scale that can reduce the prevalence
to a level that equals elimination of the disease. Significant progress has been
made in creating a manufacturing base to ensure supply at prices currently
below internationally estimated “best price” benchmark. MOHP has made the
decision to source medicines for the Hepatitis C treatment campaign exclusively
from domestic generic manufacturers. Originator companies importing or
manufacturing in Egypt have been lowering their prices to be competitive in the
private market, but their volume share will likely remain limited.
One challenge going forward for Egypt is to ensure that low prices do not lead to
inferior product quality. The support for a domestic industry is understandable,
but it should be complemented with a strict enforcement of quality standards and
a push for all manufacturers to achieve WHO Prequalification as a precondition
for participation in public tenders. This may require some consolidation and
capital investment but will also contribute to the growth of the industry by
opening export markets. Many other countries have a high burden of Hepatitis
C and Egypt, as a frontrunner, may be able to successfully export medicines as
long as they are competitive in price and quality with the Indian generics. Some
thoughts on how quality can be further assessed and addressed are summarized
in the Annex II.
40
Another issue that needs to be addressed is the monitoring of patients under
treatment across all service delivery platforms. Public sector and HIO share a
common tool, but this tool does not automatically follow up with patients who
miss their final test to confirm “sustained response.” In the private sector, there
is no follow-up system in place, therefore there will be no data on how many
patients have been successfully treated and how many will relapse. Strengthening
the existing monitoring system and developing a (linked) system for the private
sector jointly with manufacturers and providers should have a high priority.
Otherwise the treatment campaign will become more vulnerable against attacks
on its effectiveness.
Treatment Journey in the Public Sector
Patient steps:
There are currently two public payers involved in the treatment program. The
first being the NCCVH itself and financed mainly through the general budget
and to a lesser extent by donations through large national CSOs. It caters to
those who are not eligible for treatment under HIO. The second is the Health
Insurance Organization (HIO), which serves those affiliated with its various
coverage schemes (mainly civil servants, poor widowed house-wives, farmers
and a small part of the formal private sector). Patients have to go to the websites
affiliated with the appropriate schemes for self-registration.
1. NCCVH National program of MOHP: (www.nccvh.org.eg/)
The website will request simple basic personal info as: (i) National ID number;
(ii) Full Name; (iii) Place of residence; (iv) Governorate of residence; and (v)
a mobile phone number. A security verification code must also be entered to
prevent spam registrations (Figure A).
41
Figure A: Screenshot for required personal data at the NCCVH’s website
Source: NCCVH
Within one or two business days, and using his/her national ID number as an
identifier, the patient must revisit the site to check on his reservation status. Once
a unique reservation number detailing the name and address of the assigned
center is created, two documents have to be printed. The first document (Figure
B) details the reservation time, assigned center, and some general procedural
guidelines. The second (Figure C) lists the laboratory test results that the patient
must bring with him/her to the appointment. If the patient was not able to do
the tests before arriving to his/her appointment, he/she may do them at the same
designated center for a very modest user-fee, but ultimately would consume more
waiting time. The system will also send a text SMS to the patient’s mobile phone
listing the main details and requirements for his appointment.
Appointment dates and waiting time do vary according to various criteria: (i)
capacity of a specific treatment center; (ii) demand on a specific treatment center;
and (iii) availability of testing equipment in the center. At the beginning of the
program, the earliest a patient could obtain an appointment was at an average of
3-4 weeks after the registration process. However, in October 2016, the Minister
of Health and Population announced that patients could obtain an appointment
within 3-4 days.
42
Figure B: details the reservation time, allocated center and some general procedural
guidelines
Source: NCCVH
43
Figure C: Lists the laboratory test results that the patient must bring
Source: NCCVH
Advantages of the NCVVH system:
■ A fast process with 1-2 business days to obtain an appointment with a
hepatologist.
■ Requires very limited personal patient data.
■ Apart from a minimal user-fee for some of the services offered at the facilities,
the system and subsequent treatment is free of charge.
■ The system contains a substantial amount of guidelines, FAQ’s, etc. that satisfies
the majority of concerns on the part of the patients.
■ Directs the patient to a specific clinic/center at a specific date and time, thus
avoiding unnecessary waiting times at the facilities with minimal work-life
disruptions and/or discomfort to the patients.
44
Disadvantages of the NCVVH system:
■ A large portion of the general public is computer illiterate, thus preventing
access to the system unless they seek the aid of a friend, relative or a computer
shop to help them with the registration process.
■ Many patients do not come back within 1-2 business days to check on their
appointment status leading to a big number of missed or overdue appointments.
■ The text message is not always received, especially in rural areas where mobile
phone coverage is patchy.
■ The designated clinic on the website is not always geographically close to the
patient, which may cost the patient substantially in transportation costs on top of
the physical exertion associated with commuting.
■ Many patients do not reside on the address shown on their ID cards, which is
a major factor in determining which center/facility he/she should go to, creating
a huge logistical transportation problem for them with a substantial number of
requests to change the facility to another one later on.
■ For some centers, the appointment comes very soon to patients, hence not
allowing them to prepare the required documentation in time before their
appointment is due.
■ Similarly, HIO affiliated patients would have to register through the HIO main
website: http//www.hio.gov.eg/Ar/Pages/sof.aspx
It is worth mentioning that HIO affiliated patients must self-identify their
coverage status. This is fairly easy, since most of them are already contributing
premiums through their payrolls to HIO and have already obtained an HIO card.
The HIO patients would follow more or less the same protocol of the NCVVH.
They are requested to follow a general instructions page followed by a registration
page as in Figure D and Figure E. Similar to the NCCVH, only basic personal
info is required. Further, HIO operates its own network of service providers
all around the country. Some of those provision outlets (clinics, hospitals, etc)
include dedicated liver disease treatment center to which patients are directed.
45
Figure D: HIO general instructions
Source: HIO
Figure E: HIO registration page
Source: HIO
46
Also similar to NCCVH, a page displays the required lab test results for patients
to acquire an appointment (Figure F). Notably, the list of required lab tests is
more extensive on the HIO than the NCCVH website. However, a larger portion
Figure F: HIO required lab tests
of patients with HIO coverage did go for testing at HIO facilities rather than
NCCVH centers owing to their insured status under HIO.
Figure F: HIO required lab tests
Source: HIO
Treatment compliance and stay on therapy:
Once on treatment, more than 96 percent of patients complete the 3 or 6 months
regimens, with very few drop outs due to adverse events, no shows, or change
of mind. Nonetheless, as dispensing of medicines is done on a monthly basis
in an effort to boost compliance, many patients tend to come in late for their
monthly rations—as many as 20 percent in some centers. The average delay for
these patients is 5-7 days. Another compliance issue reported by hepatologists is
that some patients tend to take the pills for only 28 days and drop the remaining
2-3 days at the end of the month, thinking that treatment is only for 4 weeks (28
days) per month.
47
Hepatologists also noted that because of the seriousness of the disease and
increased awareness, the compliance and adherence to treatment were generally
high among patients. In some instances at the beginning of the treatment
program, stock-outs have led to some patients switching the brands of medicines
in the midst of their treatment course or having interruptions of up to weeks in
some cases. This has adversely affected their treatment outcomes.
Switching intentionally between different regimens was only permitted under
the program if there was no response from treatment or if the patients starts
showing intolerable adverse events as: Anemia, gastric pain or skin rashes.
Stopping treatment (treatment cessation) is mainly done by hepatologists if the
patient becomes advanced cirrhotic.
Monitoring and SVR:
Monitoring is done via the Serologic Viral Response (SVR) test, considered by
hepatologists to be the best tool to evaluate successful treatment. It is usually
done at month 1 (M1), month 3 (M3) and month 6 (M6). An ‘end of treatment
SVR” (M3 of initiating treatment) means that the patient is virus free. An SVR at
M6 confirms the eradication of virus from the human body (3 months after end
of treatment). SVR at M9 and M12 are sometimes also requested.
Treatment Outcomes:
According to experts and drug makers, there is not much difference in outcome
among generic or brand medications. However, studies performed under the watch
of NCVVH on their own patients indicated a minute difference between branded
medicines at 98 percent SVR at six months vs. the locally manufactured products
showing SVR rates of 92 – 95 percent at six months for non-cirrhotic patients. For
cirrhotic patients, SVR rates at six months hovered between 70 and 85 percent.
Those figures are usually higher if treatment is extended longer to 6 months.
Owing to the relatively cheap and affordable PCR test required to check on the
final SVR, as many as 50 percent of patients go for testing at local community
laboratories and do not come back to the treatment centers for final checks.
This pattern subsequently is causing a huge disruption in obtaining data on the
outcomes of treatment.
48
Dealing with Relapsers and Non-responders:
In case of no response or relapse, which affects less than 10 percent of the total
patient volume, hepatologists tend to switch to another protocol with a longer
duration (six months rather than three), with the addition of RBV.
“Relapsers and non-responders are not a problem anymore, sometimes the
Hepatologists fail to treat them and it is time for more experienced Hepatologist
to interfere which usually works” – Dr. Gamal Esmat
Re-Infection:
Re-infection is not common. However, due to the young age of the program, not
many re-infected cases have been encountered. Viral mutation is not currently an
issue and is perceived as falling within very limited occurrences.
Treatment Options in the Private sector
Egypt has a high rate of Dual Practice (medical doctors working in multiple
hospitals/clinics simultaneously). There are no official estimates, but some
studies estimate the phenomenon to include nearly 85 percent of all practicing
doctors (see for example: Rabie 2014; World bank 2013). Patients bypassing
the primary healthcare level and/or general practitioners is the mainstay of the
private medical provision market in Egypt. Most private clinics offer walk-in or
appointment services for secondary and sometimes tertiary treatment (World
Bank 2015). Hepatologists offering treatments for viral hepatitis follow the same
route. Most prescribed medicines would have to be paid for OOP by the patient
through a community pharmacy. For the purpose of this study, interviews were
conducted with seven medical doctors specialising in the field (as discussed
earlier) to get their perspective on the behaviour and treatment regimens used in
the private market. The detailed questionnaire could be found in Annex I.
Hepatologists noted that CHC patients in the private sector fall into one of
two categories once they are informed of their condition:
1. Concerned Patients: These patients are generally concerned with their condition,
future complications, and the costs associated with therapy. Most of the time, the
physician’s response is to reassure them that the new regimens are relatively safe,
tolerable, of shorter duration and less expensive than previous regimens.
49
2. Indifferent Patients: These patients are usually indifferent to their diagnosis
because serious symptoms have yet to manifest. Physician generally try to
educate these patients on the consequences of inaction and raise awareness of
how seeking treatment early will minimize the risk of complications, costs of
treating those complications, and the possibility of infecting loved ones.
“Once, I have seen father and 3 sons and 1 daughter, all infected with HCV
and upon investigating the reason, it turned out that they thought it’s because
all of them are using the same sanity bathroom tools. What was really strange is
that the father was willing to get treatment for himself and his 3 sons but not the
daughter!! And he explained that she will cost him treatment fees and she is not
productive nor will be working, so there was no need to treat her!! The only way I
was able to convince him is by telling him… what if you treat your sons and your
daughter re-infects them again? and that was the only way I convinced him,” said
one of the Hepatologists.
The treatment options that were available at the time of the study for eligible
patients were:
1. Sofosbuvir ± RBV (Brand)
2. Sofosbuvir ± RBV (Generic)
3. Sofosbuvir + Daclatasvir ± RBV (Brand)
4. Sofosbuvir + Daclatasvir ± RBV (Generic)
5. Harvoni ± RBV (Brand)
6. Harvoni ± RBV (Generic)
7. Sofosbuvir + Olysio ± RBV (Brand)
8. Paritaprevir/Ritonavir + Ombitasvir (Qurevo) ± RBV (Brand)
50
Treatment Choice in Private Sector:
The market shares reported in Table 10 reveal a dominance by the generics.
At the time of this study, the SOFO+DACLA generic regimen had 59 percent of
patient share, followed by Harvoni (generic). Olysio had been relatively popular
until December 2015 before declining dramatically due to the announcement
of new generic treatments with similar response rates. However physicians still
prefer Olysio for non-responders and relapsers as of this writing. Physicians
normally prescribe the regimens for 3 months, or six months if the patient is
cirrhotic (without RBV). If the patient is on dialysis or has CKD stage 4, physicians
tend to prescribe the Paritaprevir/Ritonavir + Ombitasvir (Qurevo) regimen for
3 months. Although the Paritaprevir/Ritonavir + Ombitasvir (Qurevo) regimen
is also indicated for all types of patients, physicians tend to reserve it for renal
patients owing to the higher cost.
Table 10: perceived treatment combinations in private sector from
Hepatologists perspective
Patient
# Regimens
share
1 Sofosbuvir ± RBV (Brand) 0%
2 Sofosbuvir ± RBV (Generic) 0%
3 Sofosbuvir + Daclatasvir ± RBV (Brand) 9%
4 Sofosbuvir + Daclatasvir ± RBV (Generic) 59%
5 Harvoni ± RBV (Brand) 1%
6 Harvoni ± RBV (Generic) 16%
7 Sofosbuvir + Olysio ± RBV (Brand) 2%
8 Paritaprevir/Ritonavir + Ombitasvir (Qurevo) ± RBV (Brand) 5%
9 Others (non-systemic treatment) 7%
51
Treatment Initiation, Continuation and Supply in the Private
Sector:
Physicians report that nearly 80 percent of patients are eligible for therapy with
the abovementioned regimens. The remaining 20 percent are ineligible mainly
because they have conditions for which treatment with DAAs cannot be initiated.
Those conditions usually include severe liver failure, irresponsive ascites, or
encephalopathy. Treatment for the second category would usually focus on
treating the complications themselves in an effort to stabilize the patient.
Most of the times, hepatologists give patients the choice of getting treatment
through the public system (by enrolling through the NCCVH website) or buying
it OOP. Due to the declining cost of treatment, patients in 2015 and early 2016
initially bought these medicines from community pharmacies rather than waiting
in the public system. However, since July 2016, more and more patients have
opted to obtain their medicines from the public system owing to the decreased
waiting times.
Physicians were also asked about the main challenges facing patients seeking
treatment in the public system. Table 11 lists the main findings.
52
Table 11: Perceptions of physicians on the challenges facing the patients to receive
treatment in the public system
Percentage of
Challenges facing patients under the two Physicians perceiving
#
public insurance systems: this as main challenge
in the public system
The system is too complicated to be
1 43%
understood
The insurance protocol doesn’t fit the
2 86%
patient condition
3 Not receiving the complete dose 0%
4 Availability of the prescribed drug 29%
The prescribed drug is not listed in Hospital
5 43%
drug list
The pharmacist switches to a generic or
6 0%
different brand
Too much procedures and time to receive
7 100%
the medications
8 Stock outs 71%
9 Limited numbers of qualified physicians at
57%
the examination place
“In my private clinic I give the patient the choice, I tell him you can go get
the treatment from the Public sector or buy it from the market, either brand or
generic, normally they say that they will get the brand, however when I tell them
the prices of both brands and generics, they begin to ask about the success rates
and when I illustrate that both got exactly the same response rate, they go for the
generic”—Dr. Gamal Esmat.
53
Sales retail analysis in the private sector:
There are no official data on pharmaceutical sales in Egypt. Most data are derived
from the IMS, which is a global benchmark for pharmaceutical sales around the
world (IMShealth). Nevertheless, the data is self-reported by the pharmaceutical
industry and is not verifiable. Initial data for Egypt has shown that the sales
of DAAs are almost split between private and public markets, unlike the early
years of IFN treatment, where the market was driven by the public sector. As
of September 2016, data showed that enough DAAs were sold in both markets
enough to treat 850,000 in 2016 alone. It is also worth mentioning that some
public centres may offer patients the option to buy medicines OOP from their
affiliated pharmacies at a lower price than in the private community pharmacies
i.e. not paid for by public funds. No records are kept for those patients, but
estimates suggest that nearly 50,000 have used this option. This may explain the
markedly higher IMS sales figures at the public facilities than the private sector.
Recently, many tourist agencies, realizing the leadership Egypt has shown in
treating CHC, have collaborated with leading private hepatitis clinics/centres to
create a medical tourism market for CHC in Egypt. The idea is to target CHC
patients from developed countries, where prices of DAAs are extremely costly, to
buy tailored tourism-treatment packages in Egypt at a fraction of the costs those
patients would incur in their home countries. Many are still debating the legality
of such a move, especially when it comes to the manufacturing agreements with
international pharmaceutical brand owner companies.
54
Recommendations
The following section includes the author’s recommendations for improving
the treatment program to aid in the elimination of CHC in Egypt:
1. Enforce the implementation of the National Plan of Action for Prevention,
Care and Treatment of Viral Hepatitis – Egypt. The plan, launched in
2014, enjoys a unanimous support by most stakeholders (Government,
Development Partners & CSOs) as the road that Egypt must follow to
combat and eliminate the disease. However, the lack of (i) costing of the
listed activities, (ii) identification of responsible implementing entities, and
(iii) development of relevant monitoring indicators has prevented local
and international partners from offering further support. Therefore, it was
imperative that such components be included in the plan. The World Bank
in collaboration with WHO have undertaken this technical endeavour to
support the Egyptian National Plan of Action.
2. Set a realistic target for elimination. Given current strong political support
for the program, many ambitious target dates have been proposed to reach
elimination. The range is large, with some optimistic views suggesting only
3 to 4 years to reach elimination, while other less optimistic views foresee
a need of 10 to 12 years. Accordingly, any forecasts should be based on a
set of realistic factors, including but not limited to : (i) a thorough forecast
analysis of the capacity to conduct national screening efforts that would
ultimately feed patients to the treatment program; (ii) an analysis of the
capacity to reduce the number of new infections through scaling-up the
quality and quantity of measures to decrease the spread of disease; (iii) a
stock-taking of the available and possible future financing resources for the
components of the program required for sustainability; and (iv) a detailed,
time-based, cost-prioritized version of the national plan of action for the
prevention, care and treatment of viral hepatitis in Egypt to reflect the
different roles and responsibilities for those involved.
3. Collaborate with the business private sector. The NCCVH should
encourage privately owned or parastatal firms, companies and businesses
55
to initiate screening and treatment programs for their own employees as
well as initiate a Community Service Initiative to sustain the same costs for
citizens in specific under-developed areas or for disadvantaged population
groups. Current Egyptian laws permit a certain number of tax-breaks for
firms adopting such initiatives. Notwithstanding, those activities would
have to be coordinated with NCCVH to coordinate efforts and prevent any
duplications.
4. Widen the screening program campaign: This analysis started in March
2016, during the peak of the influx of already diagnosed CHC patients
to treatment centres. This high flow of patients was understandable in
the context of previously diagnosed patients seeking cures once DAAs
were available. Nevertheless, and as anticipated, by the time these
recommendations were drafted, Egypt had managed to treat 800,000
patients and cut the waiting list of patients awaiting treatment. By the end
of 2016, the number of patient visits to treatment centres had dropped to
2000 to 3000 patients a day. To maintain the rigor of the treatment program,
Egypt needs to actively look for dormant infections among its population.
This will have to be achieved through adopting a vigorous screening
program.
The Prime Minister, based on the recommendations of MOH, issued a
decree in August 2016 specifying specific population categories as target
groups for the first phase of such a screening program. They include: (i) all
healthcare workers; (ii) all admitted cases to public hospitals regardless of
diagnosis; (iii) all university students; (iv) all males admitted to compulsory
military service; (v) all patients on dialysis; and (vi) all persons donating
blood. No plan or estimated costs related with the screening efforts were
published, nor were future plans for expansion to other groups announced.
Therefore, it is imperative that those missing elements be examined.
Further, high prevalence (e.g. persons older than 59 years of age) and
higher risk groups (e.g. IV drug users) need to be prioritized in the next
phases of the screening program. Also, given the modest sensitivity and
specificity of the rapid screening tools available in the market, a well
informed and researched decision should be made on whether to use those
56
tools for the national screening program or revert to more sophisticated
and costly in-lab testing. The latter raises additional logistical challenges
for blood sample collection, transportation, storage and an adequate feed-
back mechanism of test results to the tested subjects.
5. HCV stakeholders bonding. The Ministry of Health should arrange a
quarterly meeting between the NCVVH, the pharmaceutical industry, the
pharmaceutical syndicate (representing private community pharmacies)
and active NGOs to provide for coordination in terms of: (i) review of
pharmaceutical delivery and sales data; (ii) forecasting and estimating
the future needs of the program; (iii) resolving pending administrative
and financial issues; and (iv) communicating the anticipated changes in
treatment protocols early on for early adoption by the industry.
6. Apply high quality standards (GMP) for local manufacturing. With the
continuous drop of the prices of locally manufactured DAAs, risks of
lower quality generics will increase. The MOH, and through its EDA
arm should ensure that the pipeline of products, as the backbone of the
program, maintain an acceptable level of efficacy and safety to ensure
cure rates remain on par with branded medicines. GMP practices should
be encouraged and gradually mandated from local producers. However,
the economic viability of the local industry and maintaining a competitive
market environment should be considered whenever any regulatory action
is being planned. Annex I illustrates in some detail options to verify the
quality of Egyptian generics used in publicly financed treatment campaigns.
Support the local pharmaceutical Industry. The industry is generally
7.
prosperous. However, most pharmaceutical companies in Egypt have
to endure dual difficulties. First, the general investment climate in the
country affects all kinds of industries, e.g. the lengthy bureaucratic
processes as well as a foreign currency crunch issue makes importation of
active pharmaceutical ingredients (APIs) a challenging endeavour. Second,
the pharmaceutical industry cannot freely price their products, as Egypt
imposes a statutory pricing mechanism, yet a prospering counterfeit market
hinders its sales and product safety. Therefore, Egypt should support the
industry in combating these underlying factors that threaten its business
57
and patient safety. Further, companies should be encouraged to undergo
WHO pre-qualification process to capitalize on growing export markets
as other low and middle income countries expand treatment programs.
Lastly, approval, registration and pricing processes for newer molecules
should be streamlined and fast-tracked for companies to be able to provide
the newer medicines in proper quantities to the market.
8. Motivate patients to do End of Treatment SVR (M6). To overcome the
problem of patients not returning for SVR (M6) testing, many strategies
could be adopted to incentivize patients towards completing their
treatment and testing cycle. Global country experiences have provided us
with innovative ways of incentivizing patients, including the following:
a. Offer a free credit to the mobile phone accounts of patients who come
back to do the M6 test.
b. Waive the user fees for another infected person coming for treatment
who is referred by any of the patients who do the M6 test.
c. Offer generous free points to the “Food-subsidy” card of patients
completing the M6 tests.
d. Restrict the issuance of the “Cure Certificate” to those who complete
the M6 test.
9. Strengthen the role of the Hepatitis Unit at MOHP. The hepatitis unit
was created through a ministerial decree in late 2015 to function as a
coordination hub for the various activities that aim to prevent, control and
treat viral hepatitis C in Egypt. However, the unit is currently tasked with
conducting many operational activities for the program. This unit should
focus on its main objective of being a coordination body rather than a
direct implementation arm. The monitoring and evaluation task for the
various activities under the program should be assigned to the unit. The
unit should also be properly staffed with adequate technical capacities that
would enable it to perform its duties. The unit staff should be supported
in terms of technical capacity building and an enabling governance
atmosphere.
58
10. Enable the NGOs to work where they are most effective. Many large
NGOs have been instrumental in supporting the program in terms of
(i) providing adequate funding through donation flows; (ii) supporting
and implementing awareness campaigns for combating the disease; and
(iii) providing logistical and infrastructure support to some elements of
the program. Nevertheless, NGOs are persistently asked to offer support
in areas outside their sphere of optimal effectiveness. To optimize their
contributions, NGOs should have the freedom to support the components
of the program that best fit with their strategy and capabilities. The
government can support those remaining areas that lay outside the sphere
of NGO capabilities.
11. Initiate affordability programs for the private market. Despite treatment
becoming progressively more accessible and affordable, many patients
will still prefer to obtain their medicines from the private domain. This is
based on experience from other health programs where patients insisted
on resorting to paying out of pocket for their treatments (e.g. diabetes
and oncology treatment, etc.) despite readily accessible and affordable
treatment within public facilities. At the same time, the prices of the newer
generic classes of DAAs remain elusive to many middle and low income
Egyptians. It is therefore prudent to find innovative ways of making those
medicines affordable to those groups. International experience brings
many successful initiatives in that regards, and Egypt should consider
adopting some of them. One simple example, which could be supported by
the pharmaceutical industry and local NGOs, is to initiate an installment
payment mechanism, where the cost of the medicines is stretched over a
range of months with no or highly subsidized interest rates.
12. Do Not Forget HBV. With 800,000 patients with no definitive treatment,
HBV infected patients still pose a risk and a burden on the health status and
economy of Egypt. Egypt added HBV vaccinations to its EPI program nearly
two decades ago. However, vertical transmission (from pregnant mothers
to their babies) continues. The zero-dose regimen (given to children right
after birth) should be considered, especially since the price of the vaccine
is very modest. Further, efforts to vaccinate adult and high risk groups
59
should be further encouraged. Lastly, chronic treatments for HBV should
be also covered by the current financial protection mechanisms (HIO and
Payment on the Expense of the State) to minimize complications and their
pertinent economic costs.
13. Document the experience. In October 2016, WHO celebrated the cure of
1 million patients worldwide from HCV. Of those, 800,000 were in Egypt
alone. This achievement should be celebrated and a source of much joy
for those involved in this program. Worldwide, many countries are now
looking towards Egypt for experiences and best practices. However, little of
Egypt’s experience has been documented properly. The national program
and development partners should strive to document every step for that
purpose. This will further strengthen Egypt’s leadership. However, the
benefits reaped from this process are not limited to the reputational gains;
rather economic gains could be achieved through (i) opening up export
markets for locally manufactured DAA generics, (ii) boosting medical
tourism revenues; and (iii) providing consultancy expertise to growing
programs in other countries.
14. Automate the “Cure Certificate” process. The practice of handing treated
patients a “cure certificate” displaying his or her new status has helped
alleviate the discrimination some patients face in employment and work
visa issuance. This certificate comes in great demand, and hence, is liable
for forgery and corruption in a parallel illegal market. Therefore, we
recommend developing a online “cure certificate database” with virtual
access for entities requiring confirmation of the patient cure status. The
national ID number could act as a unique identifier. Proper patient consent
to listing his/her name openly should be obtained before the end of the
treatment process.
60
Annex I
Quantitative perception analysis on CHC treatment Journey (Hepatologists
perspective)
The following section displays the actual results obtained from a small survey of
seven leading hepatologists. The data are completely based on their professional
experiences with patients in their private settings, i.e. private clinics and hospitals.
Below are the tabulated grouped answers, averages, based on the quantitative
questionnaire that was used:
Average number of patients in total seen by a single Hepatologist in the private
sector in a typical month, for any condition across all care settings? (Excluding
multiple visits by the same patient. Please provide your best estimate.)
Total number of patients seen in a typical month 500
Average number of HCV patients seen in a typical month by Hepatologists’,
regardless of whether they are treated with active prescription therapy?
Number of HCV patients seen in a typical month 150
Percentage of HCV patients’ age ranges:
# Age Ranges Percent HCV Patients
1 0-17 1%
2 18-45 43%
3 46-65 45%
4 65+ 10%
61
Gender split of HCV patients:
# Gender % HCV Patients
1 Male 59%
2 Female 41%
Percentage of HCV patients having the following co-morbid conditions:
% of HCV patients
# Co-morbid Conditions
with…
1 HIV positive 0%
2 Hepatitis B 7%
3 Cardiovascular Disease 14%
4 ESRD Disease (patients on Dialysis or Stage 4 CKD) 3%
5 Psychiatric Disorders (i.e. Depression, etc.) 6%
6 Diabetes 29%
7 Other co-morbidities (HTN, Obesity, and Anemia) 23%
8 None 42%
Percentage of HCV patients referred to physicians’ office from another physician
for their HCV condition:
# Source % HCV Patients
1 Referred-in from another physician with an HCV
37%
diagnosis
2
Diagnosed with HCV by you 63%
62
Of those Hepatitis C patients that are referred to physicians’ office, what
percentage are referred from each of the following sectors:
Percent HCV Patients Referred
# Source
From…
1 Public sector 21%
2 Private sector 79%
3 Other (Specify) __________________ 0%
Of patients following up in the physicians’ clinic, what are the percentage of
patients getting their treatment from the following places on average, and what is
the time period required for a referral to your office to be admitted for treatment?
(Response is in days, representing the period between a patient’s referral to
private office until s/he receives a treatment):
No. of days from
% of being diagnosed with
# Source
patients HCV till receiving a
treatment
1 Health Insurance Organization 22% 157 Days
2 MOH Insurance 32% 205 Days
3 Private Insurance 3% 13 Days
4 Companies / big accounts 2% 1 Day
5 Military / Police hospitalls 1% 21 Days
6 Out of Pocket / Self-Pay 38% 1 Day
7 OOP (Subsidized value of brand) 2% 1 Day
63
Patients’ treatment type classification at private clinic:
% HCV
# Type of visit
Patients
Therapy Naïve (Diagnosed patients that have never
1 26%
been treated and may be treated in the future)
Currently Treated (Diagnosed patients that you are
2 41%
currently treating)
Successfully completed therapy (Previously treated with
3 30%
HCV therapy successfully, sustained viral response (SVR)
Relapsed from therapy (Previously treated with HCV
therapy successfully, but had un-sustained viral
4 3%
response 24 weeks after completion of therapy and who
are not currently receiving treatment)
IFN Treatment Non-responder (Previously treated with
5 HCV therapy unsuccessfully, little or no viral response during 0%
therapy and who are not currently receiving treatment)
6 Discontinued therapy for reasons other than efficacy 1%
64
What are the primary costs that patients sustain in the private sector when
undergoing HCV treatment?
% of selection
# Cost Items that patients pay in private sector of the item
from Doctors
1 Cost of medication 100%
2 Cost of managing side-effects of HCV medication 86%
3 Cost of hospital / clinic visits 57%
4 Cost of living / accommodations to be near the hospital / clinic 0%
5 Job-related / source of income costs 29%
6 Cost of travel (for office / hospital / clinic visits) 71%
7 Cost of monitoring the patient’s response to treatment / follow-up 57%
8 Cost of tests 100%
What are the perceived principal challenges facing HCV patients under Egypt’s
insurance systems that make them get treatment through OOP?
% of Doctors
Challenges facing patients under different
# selected that
insurance systems
item
1 The system is too complicated to be understood 43%
2 The insurance protocol doesn’t fit the patient condition 86%
3 Not receiving the complete dose 0%
4 Availability of the prescribed drug 29%
5 The prescribed drug is not listed in Hospital drug list 43%
6 The pharmacist switches to a generic or different brand 0%
7 Too much procedures and time to receive the medications 100%
The yearly fund (at the country expense) is not
8 71%
sufficient for the whole year treatment
65
Other (limited numbers of qualified physicians at the
9 57%
examination place)
Are physicians aware of the National Committee for the Control of Viral
Hepatitis (NCCVH)?
1 Yes 100%
2 No 0%
What is its role of NCCVH in the treatment of Hepatitis C from physicians’
perspective?
% of
Doctors
# Item
selecting
the item
1 Providing funding for patients’ HCV treatment costs 57%
2 Providing funding for HCV treatment centers’ operating costs 43%
3 Providing funding for clinical research 43%
4 Establishing treatment guidelines 100%
5 Educating health care professionals on HCV 57%
6 Educating the public/ raising public awareness of HCV 57%
7 Providing HCV screening 86%
8 Providing HCV vaccinations 0%
66
What are the various HCV diagnostic tests physicians’ conduct to confirm
patients HCV diagnosis?
% of Patients Tested for HCV
# Test Conducted
Using…
1 Liver Function Tests (ALT/AST) 100%
2 Viral load / Quantitative HCV test 90%
3 Qualitative HCV test 0%
4 Genotype Test 1%
5 Liver Biopsy 0%
6 Ultrasound 70%
7 Other (Fibroscan, CBC, ELIZA, PCR) 60%
What is the patient share of the following regiments and their duration of
treatment?
Patient
# Regimens
share
1 Sofosbuvir ± RBV (Brand) 0%
2 Sofosbuvir ± RBV (Generic) 0%
3 Sofosbuvir + Daclatasvir ± RBV (Brand) 9%
4 Sofosbuvir + Daclatasvir ± RBV (Generic) 59%
5 Harvoni ± RBV (Brand) 1%
6 Harvoni ± RBV (Generic) 16%
67
7 Sofosbuvir + Olysio ± RBV (Brand) 2%
8 Paritaprevir/Ritonavir + Ombitasvir (Qurevo) ± RBV (Brand) 5%
9 Others (non-systemic treatment) 7%
What is the treatment outcome?
# Treatment outcome %
1 Successfully completed treatment (SVR) 95%
2 Non responders 1%
3 Relapsers 3%
Discontinued therapy due to reasons other than efficacy –
4 1%
mainly due to HCC
Agreement on statements related to HCV from scale of 1 (strongly disagree) to
7 (strongly agree). Results are grouped to show the top two picks for each of the
candidates.
% of being
in the top
# Statements
2 picks for
candidates
There is very low awareness of Hepatitis C among the
1 0%
general population
There is very low awareness of Hepatitis C in the broader
2 0%
medical community
3 Hepatitis C is a less serious disease than HIV 43%
4 Hepatitis C is a less serious disease than Hepatitis B 43%
I strictly follow the HCV treatment guidelines in my
5 57%
country
Clinical trial data for treatment naïve patients can be
6 43%
extrapolated to treatment experienced patients
68
If a drug demonstrated good efficacy in treatment
experienced patients during clinical trials, I would expect
7 57%
it to demonstrate even better efficacy in practice on my
treatment naïve patients
Clinical trial data for G1 patients can be extrapolated to
8 29%
G4 patients
What are the guidelines followed by the physician?
% of
# Guidelines
Doctors
1 AASLD (American Association for Study of Liver Disease) 43%
2 EASL (European Association for Study of the Liver) 86%
3 APASL (Asia Pacific Association for Study of the Liver) 0%
4 WHO guidelines 29%
5 Egyptian National Treatment Guidelines for HCV 71%
The physicians’ perception on the results of the reform efforts in 5 year from
2016
% of
Doctors
# Reform
believing in
that reform
1 Government will increase funding for HCV treatment centers 86%
2 Number of HCV treatment centers will increase 100%
3 Government will expand education efforts around HCV 100%
Government will increase payments to HCV patients
4 100%
under MOH/Health Insurance
69
Government will increase patient access to HCV
5 100%
screening
Government will establish more aggressive HCV
6 71%
treatment guidelines
Government will increase treatment options available
7 100%
under National Health Insurance coverage
How do you as a physician learn of new products to treat HCV?
# channel % of selection
1 Internet 86%
2 Medical Journals 57%
3 Conference presentations/Symposia 86%
4 Product information via PDA/Mobile alerts 0%
5 Pharmaceutical Reps 43%
6 Continuous Medical Education 57%
7 Colleagues 0%
8 Opinion leaders 0%
Do you see local manufacturers or multinational pharmaceutical companies
as having a more important role to play in the elimination of HCV from the
country?
# Pharmaceutical % of mentioning
1 Local 77%
2 Multinational 23%
70
Annex II
Options to verify the quality of Egyptian generics used in publicly financed
treatment campaigns
The following is a list of options, from easy/low impact to more complex, to
verify and ensure that the public sector purchases generic drugs from consistent
quality, manufactured according to internationally accepted standards:
■ Informal exploration with Egyptian Drug Agency EDA (CAPA, NODCAR)
technical experts to understand the level of supervision and the degree to which
deviations from Egyptian Good Manufacturing Practices (as they should be
defined in by-laws/regulations) lead to regulatory enforcement actions.
■ Informal discussion with quality managers of Egyptian firms that have
manufacturing contracts with multinationals, on their experience and assessment
of the quality standards that are to be expected in Egypt.
■ If there are doubts that some firms may not be at acceptable levels, one could,
on a voluntary basis, invite a technical consultant firm with European credentials
to do a gap assessment. This could become a condition for future tender
participation. www.tuev-sued.de/plants-buildings-technical-facilities/fields-of-
engineering/cleanroom-technology/pharma-life-sciences shows an example of
one firm that offers these type of services – of course there are several firms so
this is not a recommendation.
■ Define a time frame (example two years) within which manufacturers must be
compliant with international GMP, certified by a regulator or a consulting firm
with the necessary credentials. This is a condition for WHO Prequalification
71
(WHO PQ), but WHO PQ has additional requirements specific to the product
for which the PQ is granted.
■ Introduce a requirement for bioequivalence studies with originator DAAs for
Egyptian generics, done by a contract research firm that has done such studies
successfully as part of WHO PQ procedures (may require to go outside Egypt).
■ Specify a time frame (for example three years) within which only WHO PQ
drugs will be accepted for public procurement, allowing manufacturers to decide
whether they want to make investments into quality or give up this segment of
the market.
■ For products that are in the WHO PQ process, there is a procedure called Expert
Review Panel (ERP, see http://apps.who.int/prequal/info_press/documents/
ERP_article.pdf ), which can be used in the interim to define whether the quality
risk associated with a specific product is acceptable. Egypt could form its own
panel with WHO expert participation and guidance, focused specifically on the
DAAs.
■ Hopefully, in the mid-term, the new EDA will build capacity to become a more
stringent regulator and join the Pharmaceutical Inspection Cooperation scheme
(PIC/S, www.picscheme.org ), which would benefit the entire sector and reduce
the need to apply specific conditions to DAAs or other lifesaving medicines.
72
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