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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