women and clinical trials in hiv women for positive action is an educational program funded and...

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


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

http://www.who.int/gender/hiv_aids/en/

http://www.paho.org/English/AD/GE/HIV.htm

Impact of religious and cultural beliefs

on women

May come from ‘hard to reach’ communities

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

Reduced access to healthcare,

education and economic resources

Language or cultural barriers

may add to lack of support

More limited scope to negotiate

frequency of and nature of sexual

interactions

Violence may increase a woman’s

vulnerability to HIV

More limited power/control to practice low-risk sexual behavior

Social and cultural differences affect how women manage HIV

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


Gender differences to therapeutic interventions

Gender differences are

found throughout medicine, due to

a number of factors

Pharmacodynamics and pharmacokineticsBiological differences in how

medicines affect the body and the way in which it processes medicines

Adverse events & toxicities

Adherence

Social reasons for delay in treatment initiation

Attitudes and behaviour

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

• 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

0.1 0.2 0.5 1 2 5 10

Male Female

Male/female gender ratio according to discontinuation or interruption of HAART

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

• 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: trial discontinuations and adverse events

• 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

Differences between men and women: discontinuation of HAART

Pharmacokinetic factors in women

• Lower bodyweight

• Fat distribution• Varying

plasma volumes

• Less organ flow

• Oestrogen has effects on plasma binding proteins

• AUC differences shown in some ARTs

• Decreased acid secretion and slower gastric emptying time with oral contraceptives and pregnancy

• Diet differences• No consistent

differences in gut CYP or p-gp

BioavailabilityDistribution

• In vitro: F>M trend

• Progesterone increases CYP2A4 activity

• Hepatic g-gp M>F

Metabolism

• Smaller organs• Hep C and

liver status

Elimination

• 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

Soon G et al. AIDS Patient Care STDS, 2012

• 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%)

• Found no statistically or clinically significant differences in outcomes by gender

Female and Male Response Rate Difference by Arm

Total

-100% -50% 0% 50% 100%

Favors Male

(n=6)

Differences between men and women: efficacy of HAART

Study design Population Findings

Open-label, multicentre study of ABC/3TC in combination with ATV or ATV/r1

55 women and 314 men

•No 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

Meta-analysis of 7 randomised controlled trials LPV/r-containing regimens2


•No substantial overall gender differences regarding efficacy, safety and tolerability

Open-label, multicentre study of ATV/r and LPV/r3


• 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


• Non-significant, sex-based differences in response to DRV/r• Probably due to higher discontinuation rates in women

Meta-analysis in women taking LPV/r-containing ART to evaluate the effect of BMI on efficacy5

485 women• No differences in efficacy across the BMI groups1. 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

Recent studies comparing efficacy of HAART in men and women

Women in clinical trials


Our knowledge is limited

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

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

Women are usually under-represented in clinical trials, however this has improved in recent years2

Many clinical trials have not been powered to detect gender differences1

Sex/gender-based differences in pharmacological characteristics of ARV agents have received little rigorous

study1

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

0

2

4

6

8

10

12

14

16

<10% 10-19% 20-29% 30-39% 40-49% 50%+

% of women in trial

Number of articles that assess the impact

of specific sex differences of HAART on viro-immunological

and clinical parameters

during HAART(Mar 02-Feb 07)

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 bidProportion of patients achieving HIV-1 RNA <400 copies/mL at week 48

22

GEMINI2

(n=337)LPV/r bid vs SQV/r bidPatients (%) with HIV-1 RNA <50 copies/mL at week 48

18 (SQV/r) – 23

(LPV/r)

ACTG A50733 (n=402)

LPV/r bid self-administered (SA) vs LPV/r qd SA vs LPV/r qdSustained 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 qdProportion 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/FTCProportion of subjects with HIV-1 RNA <40 copies/mL at Week 48

16

CASTLE6

(n=883)

LPV/r bid vs ATV/r qdProportion of patients with viral load less than 50 copies/mL at week 48

31

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 Design Outcome

DART et al, 2006(n=300)1

Africa Prospective cohort study

Virologic response over 12 months

Calmy et al, 2006(n=6861)1

Africa, Asia, Central America

Prospective multicentre cohort study

Death over 12 months

Geddes et al, 2006(n=14)1

Africa Case seriesAdverse reactions to HAART

Van Leth et al, 2005(n=1216)1

Europe, USA, Africa, Asia, North and South America

Post hoc analysisImmunovirologic response adverse reaction to HAART over 12 months

Maman et al, 2012 (n=21)2 Sub-Saharan Africa

Database analysis

Gender differences in long-term 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

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

Falcon R et al. J Women’s Health, 2011

• Aim: To enrol a high proportion of women in order to investigate sex-based differences in HAART

• Recruitment strategy included:

Site and patient toolkits

Site grants for patient support

Site-specific enrollment plans

Study branding

Involving community consultants

Subsidised child care and

transportation

Selecting study sites that

focused on women

Access to other ARV drugs

Targeted public relations

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

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


Gender balance in terms of use of pharmaceuticals

Women use more pharmaceutical resources, but are under represented in clinical trials

0

0Gender balance in terms of inclusion in clinical trials

of pharmaceuticals

Women are continually underrepresented in clinical trials

Kwakwa et al, XIX International AIDS Conference, 2012

• Proportion of women enrolled in 21 treatment-naïve HIV clinical trails (2001–2011) ranged from 8.8–35%

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

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

0%

20%

40%

60%

80%

100%

2NN

GS-

903

Abbot

t M

98-8

63

ACTG50

95

ACTG38

4

GS-

934

DM

P-00

6

Women Men

37% 26% 20% 19% 18% 14% 14% 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

% Women

14% 11% 10% 3%

Dol

uteg

ravi

r

QUAD

1

GS-

7340

QUAD

2

Guidelines for the inclusion of women in clinical studies

Regulatory authorities in Europe1 and North America2,3 are seeking to involve more women and ethnic groups in clinical trials1

• 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

2

The International Conference on Harmonization (ICH)5 recommends that a clinical study population should represent the target patient population

3

Health Canada4 (1997): guidelines about the inclusion of women in clinical trials (specifically of medications) recommends:

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

• 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 gender-based power relationships and addressing this may help improve women’s access to testing, counselling, prevention and treatment programmes

• 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 end-users (including age, sex, ethnicity)

• Women may be more biologically susceptible to HIV transmission

• Different ARV toxicity profiles have been reported

Strong scientific rationale

Strong social rationale

Heidari et al. JIAS 2011

Pregnancy is now a fact of life for women with HIV

Concerns about harming a foetus need to be minimised and balanced with the needs to include women in clinical

trials

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

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

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

• 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

The incidence of pregnancy in women living with HIV is increasing

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

Floridia M et al. Antiviral Therapy, 2006

42%

58%

0%

20%

40%

60%

80%

100%

Planned Unplanned

Enrolling and retaining women

in clinical trials


Social, logistic and scientific factors affect women’s participation in trials

The barriers are not well understood or defined

Floridia M et al. Antiviral Therapy 2006; d’Arminio Monforte et al. AIDS, 2010

• 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 decision-making

• Stigma regarding disclosing status

• Level of literacy required for consent forms and patient materials

• Time commitment for clinic visits and the length of trial

• 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

Contraception and conception barriers Other barriers

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

Women need to be empowered to make informed choices as to whether to stay in a trial

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

Understanding drivers and barriers to trial participation

Patients are

motivated by many factors

Personal benefit/gain

Wider social gain

Ease in participatio

n/safety

Some of the most

influential factors may

beSite-specific

benefits such as provision of

childcare facilities or transport costs

An opportunity to discuss

their condition

Helping to accumulate data

about a treatment that could help others in their

condition

Compensation

To fully inform women about the study, communication should be adapted to reflect the specifics of a trial and the unique

drivers and challengesthat women face

Individuals who make fully informed decisions about study participation are more likely to show commitment and

compliance to a trial

Call to action

Benefits to their daily

lives

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

How easy is it for women to participate?

e.g. inclusion and exclusion criteria, child

care, conception restrictions

Is there a clear call to action? e.g. why should women get involved and

how can they make a difference

Actin the interests of all patients at all times

Knowthe challenges and barriers women face

Think from a woman’s perspective

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


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

Registries

Observational studies

Case control studies

Post-hoc analyses

Retrospective studies

Chart reviews

Patient registries

Registries

Registries allow large-scale, long-

term data collection

generally at a lower cost than

traditional studiesThere are different types of registry e.g.

• Prospective• Retrospective• Observational

prospective

• 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

Registries typically include a larger

and more diverse group of patients

than those studied in randomised

controlled trials

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 can be used for measuring a variety of outcomes:

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


Case study 1: a potential candidate for enrolment in a clinical trial

• 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

What issues and information might an investigator discuss with a woman

potentially eligible for involvement in a study?

Case study 2: potential drop-out from a clinical trial

• 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

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?

Case study 3: pregnancy during a clinical trial

• 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

What kind of discussions might an investigator have with a woman who becomes pregnant during a study?

Thank you for your attention

Any questions?


women and clinical trials in hiv women for positive action is an educational program funded and...

Documents