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Women and clinical
trials in HIV
Women for Positive Action is an educational program
funded and initiated by AbbVie
Contents
Introduction
Overview of women and HIV
Responses to therapy: differences between men and
women
Women in clinical trials
The importance of women in clinical trials
Enrolling and retaining women in clinical trials
Alternatives to standard clinical trials
Case studies
Introduction
In 2010 an estimated 34 million people were living
with HIV globally, over half of whom were women1
The epidemiology and pattern of HIV spread in
women differs from men1
Women aged 15–24 years are as much as eight
times more likely than men to be HIV positive2
Clinical trials in HIV have tended to extrapolate
findings from male subjects to women3
Women have different biological, social and
behavioural factors that may impact on their HIV3
Many clinical trials pose significant barriers to the
participation of women3
1. UNAIDS Report. Global HIV/AIDS Response 2011;
2. Public Health Agency of Canada, 2010; 3. d’Arminio Monforte et al. AIDS 2010;
Overview of women
and HIV
Women for Positive Action is an educational program
funded and initiated by AbbVie
Biological differences between men
and women: effect on HIV
•
•
•
•
•
•
•
Biological factors are responsible for women being 2-4 times
more susceptible to HIV infection than men1-3
Women tend to be diagnosed with HIV later than men1,2
Viral loads tend to be lower in women, especially when CD4
count is high4
The rate of decline in CD4 count in women may be faster
despite their generally lower viral load5,6
Women experience more HIV-related and AIDS-defining
events than men7
Recurrent vaginal yeast infections, severe PID and increased
risk of precancerous changes to the cervix can occur in
addition to most manifestations also seen in men
In a recent Danish nationwide cohort study of people living
with HIV gender had no major impact on progression to AIDS
or mortality8
1. WHO. www.who.int/gender/hiv_aids/en/; 2. Stratton & Watstein SB, Encyclopedia of HIV and AIDS, 2003; 3. Pan American Health Organization:
www.paho.org/English/AD/GE/HIV.htm; 4. Ghandi M et al. Clinical Infectious Diseases, 2002; 5. Hubert JB et al. XIV Int AIDS Conf Abstract, 2002;
6. Patterson K et al. HIV Med, 2007; 7. Meditz AL et al. J Infect Dis, 2011; 8. Thorsteinsson K et al. Scand J Infect Dis, 2012
Social and cultural differences affect
how women manage HIV
More limited
power/control to
practice low-risk
sexual behavior
More limited scope to
negotiate frequency
of and nature of
sexual interactions
Violence may
increase a woman’s
vulnerability to HIV
Simultaneous
management of
medications, jobs,
families and other
medical and
gynecologic
problems is
challenging
Migrant women, in
particular, are often
isolated and lack
social support
Language or cultural
barriers may add to
lack of support
Reduced access to
healthcare, education
and economic
resources
Impact of religious
and cultural beliefs on
women
May come from ‘hard
to reach’ communities
1. WHO. Gender inequalities in HIV, 2008; 2. Stratton SE & Watstein SB. The encyclopedia of HIV and AIDS, 2003;
3. Pan American Health Organization. Gender and HIV. Women, Health and Development Program Fact Sheets 2008, 2008
Response to therapy:
differences between
men and women
Women for Positive Action is an educational program
funded and initiated by AbbVie
Gender differences to therapeutic
interventions
Pharmacodynamics and
pharmacokinetics
Adverse events &
toxicities
Biological differences in how
medicines affect the body and
the way in which it processes
medicines
Attitudes and
behaviour
Gender
differences are
found throughout
medicine, due to
a number of
factors
Social reasons for
delay in treatment
initiation
Adherence
Floridia M et al. Pharm Res, 2008
Differences between men and
women: initiation of HAART
•
Failure to establish outpatient treatment of HIV is
more likely to occur among female patients1
• Potential barriers include distrust and stigma, lack of
transportation, substance abuse, mental health and
housing needs
•
Female sex workers often begin treatment late2
• Vancouver-based study found 49.6% of respondents
reported barriers to accessing health services in the
previous six months
•
In a US-based study of women living with HIV3
• Substance abuse decreased the likelihood of using
HAART
• Being Caucasian increased the likelihood of using HAART
1. Mugavero MJ. Clin Infect Dis 2007; 2. Lazarus L et al. Cult Health Sex. 2012; 3. Cohen MH et al. Am J Public Health, 2004
Differences between men and
women: adherence to HAART
Male
0.1
0.2
0.5
1
2
5
10
Female
Male/female gender ratio according to discontinuation
or interruption of HAART
•
Most studies report a lower adherence rate in women1,2,3
• Occurs independently of both virological response and
rate of adverse reactions
1. Currier et al. Ann Intern Med, 2010 2. Squires, et al. CROI, 2011; 3. Nicastri, et al. J. Antimicrob. Chem, 2007
Differences between men and
women: adherence to HAART
•
•
Women are less likely to adhere to HAART
regimens if there are difficulties in taking
medication openly at home1
Lipodystrophy and poor body image can have
negative effects on adherence2-3
• Medication effects on the body and body image are
commonly listed reasons for non-adherence among
women with HIV4
•
Depression tends to be more common in women
and this is also linked to poor adherence5
• In a multicentre, observational study of 135 patients with
HIV, non-adherence was associated with worse
depression rating scale scores6
1. Sayles JN et al. J Womens Health, 2006; 2. Ammassari A et al. JAIDS, 2002; 3. Huang JS et al. AIDS Res Ther, 2006;
4. Sansone RA et al. Gen Hosp Psychiatry, 2004; 5. Turner BJ et al. J Gen Intern Med, 2003; 6. Ammassari A et al. Psychosomatics, 2004
Differences between men and women:
trial discontinuations and adverse events
•
Increased numbers of discontinuations and adverse effects in
women
Floridia et al. Pharm Res, 2008; Nicastri et al. J Antimicrob Chemother. 2007
Differences between men and
women: discontinuation of HAART
•
Women are more likely to have an interruption in
treatment than men1
• A US based retrospective cohort study reported that2
• Due to discontinuation, female sex was associated with
lower rates of treatment, increased disease progression, and
decreased survival
• After adjustment for HAART, and for achieving an
undetectable HIV-1 RNA level, the gender differences were
no longer as significant
•
In order to overcome issues of adherence, the GRACE
study utilised a flexible, female-friendly design to target
recruitment of women and prevent discontinuation
• Despite this, the discontinuation rate was still higher in
women (32.8%) than men (23.2%)
1. Touloumi et al. J Antimicrob Chem, 2007; 2. Lemly DC et al. J Infect Dis, 2009; 3. Falcon R et al. J Women’s Health, 2011
Pharmacokinetic factors in women
Bioavailability Distribution
•
•
•
Decreased acid
secretion and
slower gastric
emptying time with
oral contraceptives
and pregnancy
Diet differences
No consistent
differences in gut
CYP or p-gp
•
•
•
•
•
•
Lower
bodyweight
Fat distribution
Varying plasma
volumes
Less organ flow
Oestrogen has
effects on
plasma binding
proteins
AUC differences
shown in some
ARTs
Metabolism
•
•
•
In vitro: F>M
trend
Progesterone
increases
CYP2A4 activity
Hepatic g-gp
M>F
Elimination
•
•
Smaller organs
Hep C and liver
status
• Gender differences are found throughout medicine, based on a number of factors,
including differences in drug metabolism and adverse events
• However, there are no clear differences between the sexes regarding the clinical
progression of HIV
• Psychosocial, behavioural and attitudinal differences such as accessing treatment or
delays in initiating therapy seem to account for most differences between men and
women with HIV
Floridia M et al. Pharm Res, 2008
Differences between men and
women: efficacy of HAART
•
FDA review of registered trials
from 2000–2008
•
Results
• 22,411 HIV+ subjects in 43 RCTs for
16 ARVs; 20% women
• No significant gender differences in
treatment response at week 48,
discontinuations for AEs, lost to
follow-up, or death
• Higher rate of discontinuation for
virologic failure in males (8.15%)
than females (4.25%)
•
Favors Male
(n=6)
Found no statistically or clinically
significant differences in outcomes
by gender
Total
-100%
-50%
0%
50%
100%
Female and Male Response Rate Difference by Arm
Soon G et al. AIDS Patient Care STDS, 2012
Recent studies comparing efficacy of
HAART in men and women
Study design
Population
Findings
• No
Open-label, multicentre study of
ABC/3TC in combination with
ATV or ATV/r1
55 women and 314
men
Meta-analysis of 7 randomised
controlled trials LPV/r-containing
regimens2
492 women and
1530 men
significant gender differences in
efficacy
• Proportion of women compared to
men with HIV RNA <50 copies/mL was
lower on ATV/r when compared to ATV
• No
substantial overall gender
differences regarding efficacy, safety
and tolerability
•
Open-label, multicentre study of
ATV/r and LPV/r3
277 women and
606 men
Lower virological response in women
with both ATV/r and LPV/r
• Probably due to higher
discontinuation rates in women
•
Open-label, multicentre study of
DRV/r4
287 women and
142 men
Meta-analysis in women taking
LPV/r-containing ART to evaluate
the effect of BMI on efficacy5
485 women
Non-significant, sex-based differences
in response to DRV/r
• Probably due to higher
discontinuation rates in women
•
No differences in efficacy across the
BMI groups
1. Squires K et al. ICAAC, 2012; 2. Trinh R et al. BHIVA, 2012; 3. Squires K et al. J Antimicrob Chemother, 2011;
4. Currier J et al, Ann Intern Med. 2010; 5. Hermes A et al. IWHW, 2012
Women in clinical trials
Women for Positive Action is an educational program
funded and initiated by AbbVie
Our knowledge is limited
Sex/gender-based differences in pharmacological characteristics of
ARV agents have received little rigorous study1
Many clinical trials have not been powered to detect gender
differences1
Women are usually under-represented in clinical trials, however this
has improved in recent years2
There are conflicting results comparing virologic, immunological and
clinical responses to HAART in men and women YET guidelines for
initiating and changing ART are applied uniformly to women and men1
Little is known about how gender affects complications such as
lipoatrophy and bone density and whether these changes are due to
the treatments or the disease1
1. Meditz et al. J Infect Dis, 2011; 2. d’Arminio Monforte et al. AIDS, 2010
Relatively few studies and few women
enrolled in HIV trials
16
14
Number of articles that
assess the impact of
specific sex differences of
HAART on viroimmunological and clinical
parameters
during HAART
(Mar 02-Feb 07)
12
10
8
6
4
2
0
<10%
10-19% 20-29% 30-39% 40-49%
50%+
% of women in trial
Nicastri et al. J Antimicrob Chem, 2007
Number of women participating in HIV
clinical trials fell from 2000–2008
Struble et al, CROI, 2009; Soon et al. AIDS Patient Care and STDs, 2012
Some clinical studies include well below
50% women
Study
Outcome
% Women
KLEAN1
(n=878)
LPV/r bid vs FPV/r bid
Proportion of patients achieving HIV-1 RNA <400 copies/mL at week 48
GEMINI2
(n=337)
LPV/r bid vs SQV/r bid
Patients (%) with HIV-1 RNA <50 copies/mL at week 48
ACTG A50733
(n=402)
LPV/r bid self-administered (SA) vs LPV/r qd SA vs LPV/r qd
Sustained virologic response (<200 copies/mL) through week 48 for twice
daily vs once daily self-administered
22
ARTEMIS4
(n=689)
LPV/r bid or qd vs DRV/r qd
Proportion of patients with an HIV RNA <50 copies/mL at Week 48
30
PROGRESS5
(n=206)
LPV/r with RAL vs LPV/r with TDF/FTC
Proportion of subjects with HIV-1 RNA <40 copies/mL at Week 48
16
CASTLE6
(n=883)
LPV/r bid vs ATV/r qd
Proportion of patients with viral load less than 50 copies/mL at week 48
31
22
18 (SQV/r) –
23 (LPV/r)
1. Eron J, et al Lancet 2006; 2. Walmsley et al J Acquir Immune Defic Syndr, 2009 ; 3. Flexner et al. Clin Infect Dis. 2010 ;
4. Lathouwers et al. Antivir Ther. 2011; 5. Gathe et al. AIDS Res Hum Retroviruses. 2012; 6. Molina et al. Lancet, 2008
Relatively few studies with more than
50% women: recent examples
Study
Region
DART et al, 2006
(n=300)1
Africa
Calmy et al, 2006
(n=6861)1
Geddes et al, 2006
(n=14)1
Design
Outcome
Prospective cohort
study
Virologic response over 12
months
Africa, Asia, Central
America
Prospective
multicentre cohort
study
Death over 12 months
Africa
Case series
Adverse reactions to HAART
Europe, USA, Africa, Asia,
North and South America
Post hoc analysis
Immunovirologic response
adverse reaction to HAART
over 12 months
Sub-Saharan Africa
Database analysis
Gender differences in longterm immune response
Wester et al, 2012
(n=650)3
Sub-Saharan Africa
3x2x2 factorial
design comparing
drug regimens
Predictors of mortality with
cART
Clumeck et al, 2012
(n=425)4
Democratic Republic of
the Congo
Prospective
randomized trial
Efficacy and tolerance of
HAART regimens
Van Leth et al, 2005
(n=1216)1
Maman et al, 2012
(n=21)2
1. Nicastri et al. J Antimicrobl Chem, 2007; 2. Maman D et al. PLoS ONE, 2012; 3. Wester et al. CROI, 2012; 4. Clumeck et al. CROI, 2012
GRACE: The Gender, Race And Clinical
Experience Study
•
•
Aim: To enrol a high proportion of women in
order to investigate sex-based differences
in HAART
Recruitment strategy included:
Selecting study sites
that focused on
women
Involving
community
consultants
Subsidised child
care and
transportation
Site grants for
patient support
Site-specific
enrollment plans
Access to other ARV
drugs
Study branding
Site and patient
toolkits
Targeted public
relations
Falcon R et al. J Women’s Health, 2011
Differences between men and women:
adverse events during HAART
There is conflicting evidence in the literature on the
difference in the incidence of adverse events between
men and women during HAART
Women have a significantly greater risk of developing
lactic acidosis compared with men1,2
The nucleoside drug classes are associated with a
number of adverse events that are greater in women
vs men
1. Geddes R et al., SAMJ, 2006; 2. Boulassel MR et al., J Med Viro, 2006
Increasing the number of women in
clinical trials
Clinical researchers
• Ensure proportional representation of women in earlier
clinical studies and women-only phase III studies
• Statistically power studies to provide meaningful data on
sex differences
• Work with physicians to improve enrolment of women and
put into place strategies to address recruitment barriers
Clinical trial sponsors
• Collaborations with investigators and centres responsible
for the treatment of a high proportion of women living with
HIV
• Provision of specific tools to enhance recruitment of women
d’Arminio Monforte et al. AIDS, 2010
Journal editorial policy on reporting
gender differences in clinical trials
•
Journal editors, as promoters of ethical research
and adequate standards of scientific reporting,
should encourage inclusion of gender analyses:1
“Submitting authors are strongly encouraged to include data
disaggregated by sex... If the research study was specific to one
sex/gender, the reasons for this should be clearly stated.”
Journal of the International AIDS Society2
"The Lancet encourages researchers to enroll more women into clinical
trials of all phases, and to plan to analyse data by sex, not only when
known to be scientifically appropriate, but also as a matter of routine”
The Lancet3
1. Heidari et al. J Int AIDS Soc, 2012; 2. Author Guidelines, JIAS, 2012; 3. Editorial, Lancet, 2011
The importance of
women in clinical trials
Women for Positive Action is an educational program
funded and initiated by AbbVie
Women use more pharmaceutical
resources, but are under
represented in clinical trials
0
Gender balance in terms of
use of pharmaceuticals
Gender balance in terms of
inclusion in clinical trials of
pharmaceuticals
0
Women are continually underrepresented
in clinical trials
•
Proportion of women enrolled in 21 treatment-naïve HIV
clinical trails (2001–2011) ranged from 8.8–35%
Kwakwa et al, XIX International AIDS Conference, 2012
Women are under-represented in
clinical trials of new ARTs
•
•
•
Women are under-represented
Studies are under-powered for gender comparison
Pregnancy is either an exclusion criterion or reason for withdrawal
% Women
100%
80%
60%
40%
20%
0%
37%
26%
20%
19%
18%
14%
Women
14%
14%
11%
Men
10%
3%
Trial
n=
2NN
1216
GS-903
602
Abbott
M98-863
653
ACTG5095
1147
ACTG384
980
GS-934
509
DMP-006
450
Dolutegravir
205
GS7340
38
QUAD (1)
700
QUAD (2)
708
1. Adapted from Bartlett J. CROI, 2006; 2. Stellbrink et al. CROI, 2012; 3. Sax et al. CROI, 2012; 4. DeJesus et al. CROI, 2012
Guidelines for the inclusion of
women in clinical studies
1
2
Regulatory authorities in Europe1 and North
America2,3 are seeking to involve more women and
ethnic groups in clinical trials
3
The International Conference on Harmonization
(ICH)5 recommends that a clinical study population
should represent the target patient population
Health Canada4 (1997): guidelines about the
inclusion of women in clinical trials (specifically of
medications) recommends:
•
A representative number of women be included into
clinical trials for therapeutic products that are intended to
be used specifically by women or in heterogeneous
populations that include women
• Women should be included at the earliest stages of clinical
trial research so that potential sex-related differences are
identified and taken into consideration when planning
Phase III pivotal trials
1. EMA 2005; 2. USFDA, 2012; 3. Pinnow E et al. Womens Health Issues, 2009; 4. Health Canada, 2012; 5. EMA/ICH, 1998
Importance of women in clinical trials
Strong scientific
rationale
•
•
•
•
•
•
50% of the HIV population are
women
Biological and hormonal gender
differences
Bodyweight and fat distribution
differences and their effects on
drug absorption, distribution,
metabolism and excretion
Drugs should be tested in
populations that reflect the endusers (including age, sex,
ethnicity)
Women may be more
biologically susceptible to HIV
transmission
Different ARV toxicity profiles
have been reported
Strong social rationale
•
•
•
•
50% of the HIV population are
women
Understanding and addressing
the barriers to inclusion
Ensuring that women have
equal access to successful
treatment
Women may be more
vulnerable due to genderbased power relationships and
addressing this may help
improve women’s access to
testing, counselling, prevention
and treatment programmes
Heidari et al. JIAS 2011
Pregnancy is now a fact of life for
women with HIV
In the absence of any interventions mother-to-child transmission
rates range from 15-45%1
• This rate can be reduced to levels below 5% with effective
interventions
Many women – with or without HIV – do not plan their
pregnancies
• In 2006, 49% of pregnancies were unplanned in US2
• A Canadian study found that 56% of women with HIV who were
previously pregnant, identified their last pregnancy as being
unintended3
• A study of pregnant teenagers with HIV aged 13–19 years from
12 London hospitals found 82% of pregnancies were unplanned4
Concerns about harming a foetus need to be minimised and
balanced with the needs to include women in clinical trials
Clinical trials need to adapt
1. Mother-to-child transmission of HIV. http://www.who.int/hiv/topics/mtct/en/;
2. Finer LB et al. Contraception.,2006; 3. Loufty et al. HIV Med, 2012; 4.Elgalib A et al. HIV Med, 2011
The incidence of pregnancy in women
living with HIV is increasing
•
•
•
In a UK study of 7853 women who accessed HIV care
from 2000–2009, there were a total of 1637 pregnancies
among 1291 women
The number of pregnancies increased from 156 in
2000/01 to 450 in 2008/09
A number of factors were associated with an increased
likelihood of pregnancy:
•
•
•
•
•
Younger age
A CD4 count of 200–350 cells/mm3
Black ethnicity
Women who contracted HIV via heterosexual sex
The findings reflect not only an increase in the pregnancy
rate, but also an increase in the number of women
accessing and remaining in care
Huntington et al. AIDS, 2012
Significant proportion of pregnancies
among women with HIV are not planned
•
Among 334 women receiving ART, less than half reported their current
pregnancy as planned
•
The ART regimen at conception is frequently only suitable for non-pregnant
woman
•
Many different regimens were prescribed to women of childbearing age,
including:
•
•
ddI+d4T-based regimens (9.6%)
•
EFV-based regimens (13.5%)
Once pregnant, patients receiving
EFV or ddI often had to change
ART
•
•
(OR 13.2 P<0.001; 1.8 P=0.033,
respectively)
Physicians should consider the
child-bearing potential of this
patient group when initiating ART
100%
80%
58%
60%
42%
40%
20%
0%
Planned
Unplanned
Floridia M et al. Antiviral Therapy, 2006
Enrolling and
retaining women in
clinical trials
Women for Positive Action is an educational program
funded and initiated by AbbVie
Social, logistic and scientific factors
affect women’s participation in trials
The barriers are not well understood or defined
Contraception and conception
barriers
Other barriers
•
•
•
•
•
•
Study protocol criteria e.g. insisting
on two forms of barrier contraception
yet not providing them, thus placing
additional burden on the patient
Fear of causing harm to a developing
foetus
Exclusion criteria for pregnancy and
lactation in the face of social pressure
to bear children
Use of contraception may conflict with
beliefs
Concern about drug-drug interactions
with oral contraceptives
•
•
•
•
•
•
Policy of exclusion prohibiting
participation of potentially pregnant
women for fear of foetal harm
Blood drawing, particularly for women
who already lose blood through
menstruation
Competing role as primary family care
giver – women may not put
themselves ‘first’
Relative lack of autonomy in decisionmaking
Stigma regarding disclosing status
Level of literacy required for consent
forms and patient materials
Time commitment for clinic visits and
the length of trial
Floridia M et al. Antiviral Therapy 2006; d’Arminio Monforte et al. AIDS, 2010
Balancing ethical implications
Exposure in the first trimester of pregnancy raises a number
of ethical considerations
Risk to the
unborn child
Risk to future
generations of
women who
will not be
adequately
treated
Studies may be investigating drugs which could be prescribed in practice
during pregnancy, but still require the woman
to withdraw from the trial if she becomes pregnant
Women need to be empowered to make informed choices
as to whether to stay in a trial
Understanding drivers and barriers
to trial participation
Personal
benefit/gain
Patients are
motivated
by many
factors
Ease in
participation/
safety
Benefits to
their daily lives
Wider social
gain
Call to action
Compensation
Some of the
most
influential
factors may be
Helping to accumulate
data about a
treatment that could
help others in their
condition
An opportunity
to discuss their
condition
Site-specific benefits
such as provision of
childcare facilities or
transport costs
To fully inform women about the study, communication should be adapted
to reflect the specifics of a trial and the unique drivers and challenges
that women face
Individuals who make fully informed decisions about study participation
are more likely to show commitment and compliance to a trial
Informing women and anticipating
barriers and drivers to trial participation
What are the personal
drivers patients may have
for involvement in a study?
e.g. chance to access
investigational medication
What are the wider social
benefits of patient
involvement in a clinical
trial? e.g. helping advance
treatment for others
Is there a clear call to
action? e.g. why should
women get involved and
how can they make a
difference
How easy is it for women
to participate? e.g.
inclusion and exclusion
criteria, child care,
conception restrictions
Think
from a woman’s
perspective
Know
the challenges
and barriers
women face
Act
in the interests of all
patients at all times
Can study protocols be made more
woman-friendly?
•
Modify requirements for contraception
•
Include an open phase / follow-up for
women who become pregnant
•
Avoid ‘judgmental’ language e.g. woman
don’t ‘drop out’ due to pregnancy, they
convert to another phase of the protocol
•
Develop networks of centres that care for
large numbers of women
d’Arminio Monforte et al. AIDS, 2010
Can study protocols be made more
woman-friendly?
•
Provide referrers, centres and investigators
with guidance on how to make visits and
studies more accessible and woman-friendly1
•
•
•
•
•
•
Childcare
Transport costs
Confidentiality
Compensation for loss of earnings
Communicate findings to participants in an
appropriate way to promote further
engagement in clinical trials
i-Base and the Terrence Higgins Trust produce
information booklets which explain to patients
how clinical trials work and what issues to
consider before enrolling in one2,3
1. d’Arminio Monforte et al. AIDS, 2010; 2. THT, 2012; 3. i-Base, 2009
What happens if a woman becomes
pregnant while part of a clinical trial?
Drop-out?
Empower women to make informed decisions
• Stay on trial if protocol allows
• Convert to open-label treatment
• Treatment options if they leave the study
• Keeping in touch – follow-up visits
Alternatives to
clinical trials
Women for Positive Action is an educational program
funded and initiated by AbbVie
Randomised controlled trials
•
RCTs give the highest level of evidence when
seeking to answer a specific clinical questions with
statistical significance
•
They have their limitations:
• usually enrol a less diverse population of subjects than is
commonly seen in everyday clinical practice (e.g. fewer
women, less complicated patients)
• do not always reflect the common clinical settings in which
many people receive treatment
• often expensive and time-consuming
• good for answering specific questions, but not for
generating new hypotheses or exploring broad questions
Alternatives to randomised controlled trials
Post-hoc analyses
Retrospective studies
Chart reviews
Case control studies
Registries
Observational studies
Patient registries
Registries play an
increasing role in
providing payers and
decision-makers with
information to validate the
safety and efficacy
of interventions
reported in phase III
clinical trials
Registries allow largescale, long-term data
collection generally at
a lower cost than
traditional studies
There are different types
of registry e.g.
• Prospective
prospective• Retrospective
• Observational
Registries
Registries typically
include a larger and
more diverse group of
patients than those
studied in randomised
controlled trials
Registries can be used for
measuring a variety of outcomes:
•
•
•
•
•
•
Pooling data
Understanding natural history
Assessing day-to-day safety and effectiveness
Physician experience
Patient-reported outcomes: satisfaction, compliance
and burden of illness
Quality of care and cost-effectiveness
Women’s HIV registries
•
Example: Antiretroviral Pregnancy Registry (APR)
• www.apregistry.com
• International, prospective, exposure-registration study
established in 1989
• Collects data on birth outcomes, primarily birth defects,
following pregnancy exposures to antiretroviral therapy
•
Registries are beneficial especially when patient
numbers are large
•
Several limitations to registries e.g.:
• Passive reporting may over-represent abnormalities
• It may be difficult to determine which drug is the root of
the problem when a combination is prescribed
The Antiretroviral Pegnancy Registry. Available at: http://www.apregistry.com
Case studies
Women for Positive Action is an educational program
funded and initiated by AbbVie
Case study 1: a potential candidate
for enrolment in a clinical trial
What issues and information might an
investigator discuss with a woman potentially
eligible for involvement in a study?
•
•
•
Standard information about what a clinical trial involves in
order for the woman to make a fully informed choice
Information about childcare, what to do if she can’t make a
clinic visit, etc
Contraception inclusion criteria, what this means and what
she should do if she becomes pregnant
• Implications for the unborn child
• Implications for her
• Implications for the clinical trial
•
Details where she can get more information and advice as
required
Case study 2: potential drop-out
from a clinical trial
What issues and options might an investigator
discuss with a woman who is about to drop
out of a study because she is finding it too
difficult to make the clinic visits?
•
•
•
•
•
Her specific problems and needs avoiding any impression of blame
or disappointment for dropping out
Explore whether the centre or sponsor can provide support to help
her make the clinic visits
Provide information and support using language that is relevant to
her and her needs
Discuss her continuing treatment options should she leave the study
Reassurance that many patients do not complete a whole study but
that their participation is still valuable
Case study 3: pregnancy during a
clinical trial
What kind of discussions might an investigator
have with a woman who becomes pregnant
during a study?
•
•
•
•
•
•
Answer questions about any effects that the trial drug might
have on her pregnancy
Discuss the options of continuing with the trial, e.g. converting
to an open phase of the protocol if allowed
Follow up during and after the pregnancy
Continuing treatment options
Avoid any impression of blame or disappointment for
dropping out
Reassurance that patients often do not complete a whole
study but that their participation is still valuable
Thank you for your
attention
Any questions?
Women for Positive Action is an educational program
funded and initiated by AbbVie