Mental Health Impact of Early Stages of the COVID-19 Pandemic on Individuals with Pre-Existing Mental Disorders: A Systematic Review of Longitudinal Research.

In view of disease-related threats, containment measures, and disrupted healthcare, individuals with pre-existing mental illness might be vulnerable to adverse effects of the COVID-19 pandemic. Previous reviews indicated increased mental distress, with limited information on peri-pandemic changes. In this systematic review, we aimed to identify longitudinal research investigating pre- to peri-pandemic and/or peri-pandemic changes of mental health in patients, focusing on the early phase and considering specific diagnoses. PsycINFO, Web of Science, the WHO Global literature on coronavirus disease database, and the Cochrane COVID-19 Study Register weresearched through 31 May 2021. Studies were synthesized using vote counting based on effect direction. We included 40 studies mostly from Western, high-income countries. Findings were heterogeneous, with improving and deteriorating mental health observed compared to pre-pandemic data, partly depending on underlying diagnoses. For peri-pandemic changes, evidence was limited, with some suggestion of recovery of mental distress. Study quality was heterogeneous; only few studies investigated potential moderators (e.g., chronicity of mental illness). Mental health effects on people with pre-existing conditions are heterogeneous within and across diagnoses for pre- to peri-pandemic and peri-pandemic comparisons. To improve mental health services amid future global crises, forthcoming research should understand medium- and long-term effects, controlling for containment measures.

Effectiveness and cost-effectiveness for the treatment of depressive symptoms in refugees and asylum seekers: A multi-centred randomized controlled trial.

Background: Current evidence points towards a high prevalence of psychological distress in refugee populations, contrasting with a scarcity of resources and amplified by linguistic, institutional, financial, and cultural barriers. The objective of the study is to investigate the overall effectiveness and cost-effectiveness of a Stepped Care and Collaborative Model (SCCM) at reducing depressive symptoms in refugees, compared with the overall routine care practices within Germany's mental healthcare system (treatment-as-usual, TAU). Methods: A multicentre, clinician-blinded, randomised, controlled trial was conducted across seven university sites in Germany. Asylum seekers and refugees with relevant depressive symptoms with a Patient Health Questionnaires score of ≥ 5 and a Refugee Health Screener score of ≥ 12. Participants were randomly allocated to one of two treatment arms (SCCM or TAU) for an intervention period of three months between April 2018 and March 2020. In the SCCM, participants were allocated to interventions tailored to their symptom severity, including watchful waiting, peer-to-peer- or smartphone intervention, psychological group therapies or mental health expert treatment. The primary endpoint was defined as the change in depressive symptoms (Patient Health Questionnaire-9, PHQ-9) after 12 weeks. The secondary outcome was the change in Montgomery Åsberg Depression Rating Scale (MADRS) from baseline to post-intervention. Findings: The intention-to-treat sample included 584 participants who were randomized to the SCCM (n= 294) or TAU (n=290). Using a mixed-effects general linear model with time, and the interaction of time by randomisation group as fixed effects and study site as random effect, we found significant effects for time (p < .001) and time by group interaction (p < .05) for intention-to-treat and per-protocol analysis. Estimated marginal means of the PHQ-9 scores after 12 weeks were significantly lower in SCCM than in TAU (for intention-to-treat: PHQ-9 mean difference at T1 1.30, 95% CI 1.12 to 1.48, p < .001; Cohen's d=.23; baseline-adjusted PHQ-9 mean difference at T1 0.57, 95% CI 0.40 to 0.74, p < .001). Cost-effectiveness and net monetary benefit analyses provided evidence of cost-effectiveness for the primary outcome and quality-adjusted life years. Robustness of results were confirmed by sensitivity analyses. Interpretation: The SSCM resulted in a more effective and cost-effective reduction of depressive symptoms compared with TAU. Findings suggest a suitable model to provide mental health services in circumstances where resources are limited, particularly in the context of forced migration and pandemics. Funding: This project is funded by the Innovationsfond and German Ministry of Health [grant number 01VSF16061]. The present trial is registered under Clinical-Trials.gov under the registration number: NCT03109028. https://clinicaltrials.gov/ct2/show/NCT03109028.

Physicians' attitudes towards disclosure of payments from pharmaceutical companies in a nationwide voluntary transparency database: a cross-sectional survey.

OBJECTIVES: To investigate German physicians' attitudes towards and experiences with voluntary disclosure of payments by pharmaceutical companies in a public database and their impact on future decisions for or against disclosure. DESIGN: A national cross-sectional survey conducted in 2018 among physicians who voluntarily disclosed at least one payment in the German transparency regulation. SETTING: Retrospective paper-pencil questionnaire about attitudes towards and experiences with voluntary payment disclosures in the first (2015) and second (2016) years of the German transparency regulation. PARTICIPANTS: German physicians who disclosed either in the first year only, the second year only, or in both years of the transparency regulation. PRIMARY OUTCOMES: (1) The probability to disclose in 2016, predicted by physicians' experience of reactions from others in 2015, descriptive norms and attitudes towards transparency; (2) Frequency and (3) Content of reactions from others in 2015 compared with 2016. RESULTS: Data of 234 respondents were analysed (n=42, 45 and 147 physicians who disclosed in 2015, 2016 or both years, respectively). The probability to disclose in 2016 was not predicted by perceived reactions, norms or attitudes towards transparency (p>0.01). Most participants reported not to have received any reactions by patients (190/234, 81%), colleagues (128/234, 55%) or the private environment (153/234, 65%). Neither frequency nor content of reactions differed between the first and second years (scale 1-5; frequency: Mdn2015,2016 = 1.33 vs 1.00, rb=-0.17, p>0.01; content: Mdn2015,2016 = 3.00 vs 3.00, rb=0.19, p>0.01). However, media reporting, fear of reputational damage and a feeling of being defamed were mentioned as reasons for non-disclosure. CONCLUSIONS: While confirmatory analyses did not provide significant results, descriptive analyses showed that participants who voluntarily disclose payments mainly do not experience any reactions towards their disclosures but report fears about losing their reputation due to disclosures.

The Frequent Stressor and Mental Health Monitoring-Paradigm: A Proposal for the Operationalization and Measurement of Resilience and the Identification of Resilience Processes in Longitudinal Observational Studies.

Resilience has been defined as the maintenance or quick recovery of mental health during and after times of adversity. How to operationalize resilience and to determine the factors and processes that lead to good long-term mental health outcomes in stressor-exposed individuals is a matter of ongoing debate and of critical importance for the advancement of the field. One of the biggest challenges for implementing an outcome-based definition of resilience in longitudinal observational study designs lies in the fact that real-life adversity is usually unpredictable and that its substantial qualitative as well as temporal variability between subjects often precludes defining circumscribed time windows of inter-individually comparable stressor exposure relative to which the maintenance or recovery of mental health can be determined. To address this pertinent issue, we propose to frequently and regularly monitor stressor exposure (E) and mental health problems (P) throughout a study's observation period [Frequent Stressor and Mental Health Monitoring (FRESHMO)-paradigm]. On this basis, a subject's deviation at any single monitoring time point from the study sample's normative E-P relationship (the regression residual) can be used to calculate that subject's current mental health reactivity to stressor exposure ("stressor reactivity," SR). The SR score takes into account the individual extent of experienced adversity and is comparable between and within subjects. Individual SR time courses across monitoring time points reflect intra-individual temporal variability in SR, where periods of under-reactivity (negative SR score) are associated with accumulation of fewer mental health problems than is normal for the sample. If FRESHMO is accompanied by regular measurement of potential resilience factors, temporal changes in resilience factors can be used to predict SR time courses. An increase in a resilience factor measurement explaining a lagged decrease in SR can then be considered to index a process of adaptation to stressor exposure that promotes a resilient outcome (an allostatic resilience process). This design principle allows resilience research to move beyond merely determining baseline predictors of resilience outcomes, which cannot inform about how individuals successfully adjust and adapt when confronted with adversity. Hence, FRESHMO plus regular resilience factor monitoring incorporates a dynamic-systems perspective into resilience research.

Voluntary disclosures of payments from pharmaceutical companies to healthcare professionals in Germany: a descriptive study of disclosures in 2015 and 2016.

OBJECTIVE: To analyse voluntary payment reports of pharmaceutical companies to German healthcare professionals (HCPs) in 2015 and 2016 based on an industry-self-regulating transparency codex. DESIGN AND PARTICIPANTS: Cohort study of all German HCPs who voluntarily agreed that at least one payment they received in 2015 and 2016 from pharmaceutical companies is disclosed. MAIN OUTCOME MEASURES: Number of HCPs who disclosed at least one payment in the database; separated by year of disclosure and whether they disclosed once or repeatedly. Amount of disclosed payments and distribution parameters of disclosed annual payment sums per person; separated by year of disclosure und whether they disclosed once or repeatedly. RESULTS: 28 230 HCPs agreed to the disclosure of at least one payment in the database. In 2015, 19 905 HCPs agreed to the disclosure, decreasing to 15 782 HCPs in 2016. Whereas 7457 disclosed payments in both years, 12 448 disclosed only in 2015 and 8325 only in 2016. Payments of €32 426 721 in 2015 and €23 289 343 in 2016 were disclosed, that is, 27% and 23% of the total amounts spent on HCPs, respectively. Distribution of annual payments was skewed: the top 1% of HCPs disclosed annual payment sums between €17 049 and €200 194, while the median disclosed annual payment sum per person was €536 (IQR €1092). Disclosed payments were higher in male physicians and in physicians with higher academic degree. CONCLUSIONS: If voluntary, disclosure rates of payments are low and therefore only provide a fragmented picture of interactions between HCPs and pharmaceutical companies. Efforts must be intensified to ensure obligatory disclosure of all payments worldwide.

Correction: Assessment of Microstressors in Adults: Questionnaire Development and Ecological Validation of the Mainz Inventory of Microstressors.

[This corrects the article DOI: 10.2196/14566.].

Assessment of Microstressors in Adults: Questionnaire Development and Ecological Validation of the Mainz Inventory of Microstressors.

BACKGROUND: Many existing scales for microstressor assessment do not differentiate between objective (ie, observable) stressor events and stressful cognitions or concerns. They often mix items assessing objective stressor events with items measuring other aspects of stress, such as perceived stressor severity, the evoked stress reaction, or further consequences on health, which may result in spurious associations in studies that include other questionnaires that measure such constructs. Most scales were developed several decades ago; therefore, modern life stressors may not be represented. Ecological momentary assessment (EMA) allows for sampling of current behaviors and experiences in real time and in the natural habitat, thereby maximizing the generalization of the findings to real-life situations (ie, ecological validity) and minimizing recall bias. However, it has not been used for the validation of microstressor questionnaires so far. OBJECTIVE: The aim is to develop a questionnaire that (1) allows for retrospective assessment of microstressors over one week, (2) focuses on objective (ie, observable) microstressors, (3) includes stressors of modern life, and (4) separates stressor occurrence from perceived stressor severity. METHODS: Cross-sectional (N=108) and longitudinal studies (N=10 and N=70) were conducted to evaluate the Mainz Inventory of Microstressors (MIMIS). In the longitudinal studies, EMA was used to compare stressor data, which was collected five times per day for 7 or 30 days with retrospective reports (end-of-day, end-of-week). Pearson correlations and multilevel modeling were used in the analyses. RESULTS: High correlations were found between end-of-week, end-of-day, and EMA data for microstressor occurrence (counts) (r≥.69 for comparisons per week, r≥.83 for cumulated data) and for mean perceived microstressor severity (r≥.74 for comparisons per week, r≥.85 for cumulated data). The end-of-week questionnaire predicted the EMA assessments sufficiently (counts: beta=.03, 95% CI .02-.03, P<.001; severity: beta=.73, 95% CI .59-.88, P<.001) and the association did not change significantly over four subsequent weeks. CONCLUSIONS: Our results provide evidence for the ecological validity of the MIMIS questionnaire.

[There is no Season for Gifts]. / Auch zu Weihnachten keine Geschenke!

Gifts and payments from pharmaceutical manufacturers to medical doctors constitute a conflict of interest, which may lead to an undue influence on prescribing behavior. In Germany, 35 research-based pharmaceutical companies, organized in the "Verband der forschenden Arzneimittelhersteller (VfA)" paid €â€Š562 million to medical doctors and hospitals in 2016. Of these, €â€Š356 million were paid for clinical trials and non-interventional studies, €â€Š105 million for sponsored presentations and CME and €â€Š101 million went to hospitals and other organizations for sponsoring, consulting and events. This article gives a short review on the different kinds of interactions, discusses psychological mechanisms and legal aspects of accepting gifts and recommends not to accept any gifts and donations from pharmaceutical companies to avoid undue influences on prescribing behavior. There are many ways to keep up to date using independent sources of information, and independent CME-events are growing in number - examples are given.

Conflicts of Interest in Medicine. A Systematic Review of Published and Scientifically evaluated Curricula.

Objective: Conflicts of interests resulting from interactions with pharmaceutical companies are pervasive in medicine and can result in an undue influence on physicians' decision-making. The objective of this systematic review is to analyze published and scientifically evaluated curricula for medical students and residents regarding such conflicts of interest. We begin by describing the covered topics and teaching methods; afterwards we analyze the quality of the curricula using the published data on their evaluations and comparing the content with content recommended for such curricula. Methods: We searched Pubmed, PsycInfo, EMBASE, OECD, WISO, SOWI and googlescholar up to and including the 5th of September 2016. Publications describing curricula for residents or medical students on the topic of conflicts of interest in medicine and evaluating them for their effects on the participants' learning were included. We analyzed the covered topics and the teaching methods used and compared them with recommendations by the American Medical Students' Association (AMSA) and Health Action International (HAI). Results: The literature search resulted in 20 publications that fulfilled our search criteria. In five trials, a control group was used, in no trial the participants were randomized to intervention or control group. 16/20 published curricula primarily covered marketing strategies by pharmaceutical companies, especially the interaction with pharmaceutical sales representatives (PSRs). Most curricula only covered a limited number of topics recommended by AMSA/HAI. The most frequent teaching method was a group discussion, which was used in 18/20 curricula; all curricula used at least one interactive teaching method. The evaluation of the curricula was heterogeneous in results as well as design. Some publications described a change of attitudes toward a stronger skepticism regarding interactions with pharmaceutical companies. Four publications described improved knowledge, one publication described a change in behavior toward a reduction of the acceptance of gifts. Conclusion: The trials conducted to this date regarding curricula on conflicts of interests are methodologically flawed and the described curricula lack important topics beyond marketing strategies of pharmaceutical companies. In addition, there are no data so far on the sustainability of the courses' effects on participants' behavior. It is therefore necessary to develop a model curriculum that covers a broader variety of topics and to evaluate it using a well thought-out methodology to create a foundation for the further improvement of teaching conflicts of interest in medicine.

[Patient attitudes and expectations towards conflicts of interest of attending physicians]. / Einstellungen und Erwartungen von Patienten in Bezug auf Interessenkonflikte ihrer behandelnden Ärzte.

BACKGROUND: Patients can truly expect to be treated by their physicians without undue influences of secondary interests. It is not known what patients in Germany know about relationships between physicians and the pharmaceutical industry and if and how they want to be informed about these relationships. METHOD: An information sheet explaining conflicts of interest and a 19-item questionnaire were distributed to 765 patients at various medical offices and hospitals in two German cities. 80 % (n=612) of the patients completed and returned the questionnaires anonymously. RESULTS: 65 % of the patients did not know of conflicts of interest (COI) doctors may have with the pharmaceutical industry. 74 % of the patients would like to know if their doctor had obtained any benefits through contacts with the pharmaceutical industry. 71 % agreed that a disclosure would increase their confidence, and 74 % wanted their physicians to declare COI verbally to them during a consultation. 40 % would prefer a doctor who is not receiving any benefits from the pharmaceutical industry. The desire for disclosure was significantly higher in patients who had an awareness of the problems of COI (OR 4.95; 95 % CI 3.33 - 7.35). However, 35 % of the patients trusted their attending physicians anyway and did not see a need for disclosure of any COI. CONCLUSION: The majority of patients, but not all patients want to be informed about COI of their physicians. The best way to do this has yet to be determined.

Contact between doctors and the pharmaceutical industry, their perceptions, and the effects on prescribing habits.

BACKGROUND: The prescribing behaviour of doctors is influenced by the pharmaceutical industry. This study investigated the extent to which contacts with pharmaceutical sales representatives (PSR) and the perception of these contacts influence prescribing habits. METHOD: An online questionnaire regarding contact with PSRs and perceptions of this contact was sent to 1,388 doctors, 11.5% (n = 160) of whom completed the survey. Individual prescribing data over a year (number of prescriptions, expenditure, and daily doses) for all on-patent branded, off-patent branded, and generic drugs were obtained from the Bavarian Association of Statutory Health Insurance Physicians. RESULTS: 84% of the doctors saw PSR at least once a week, and 14% daily. 69% accepted drug samples, 39% accepted stationery and 37% took part in sponsored continuing medical education (CME) frequently. 5 physicians (3%) accepted no benefits at all. 43% of doctors believed that they received adequate and accurate information from PSRs frequently or always and 42% believed that their prescribing habits were influenced by PSR visits occasionally or frequently. Practices that saw PSRs frequently had significantly higher total prescriptions and total daily doses (but not expenditure) than practices that were less frequently visited. Doctors who believed that they received accurate information from PSRs showed higher expenditures on off-patent branded drugs (thus available as generics) and a lower proportion of generics. The eschewal of sponsored CME was associated with a lower proportion of on patent-branded drug prescriptions, lower expenditure on off-patent branded drug prescriptions and a higher proportion of generics. Acceptance of office stationery was associated with higher daily doses. CONCLUSIONS: Avoidance of industry-sponsored CME is associated with more rational prescribing habits. Furthermore, gift acceptance and the belief that one is receiving adequate information from a PSR are associated with changed prescribing habits. Further studies with larger sample sizes are needed.

Conflicts of interest in medical school: missing policies and high need for student information at most German universities.

OBJECTIVES: Medical students interact with pharmaceutical representatives already during medical school. The goal of this study was to find out: Do policies exist at German medical faculties that govern the interactions between medical students and pharmaceutical representatives, do schools offer courses on the subject and do students attend these courses? And What are the attitudes of medical students concerning the role of pharmaceutical companies in medical teaching? METHODS: All 36 German medical faculty deans and 1151 medical students at eight German universities were asked to complete a questionnaire of 4 and 7 questions, respectively, regarding the above mentioned topics. RESULTS: 30 (83.3%) deans and 1038 (90.3%) medical students filled in the questionnaire, respectively. According to the deans' answers, only one school had a policy concerning conflicts of interest and one had a policy governing the interactions between medical students and industry. 8 (26.7%) deans showed an interest in constructing a policy or educational an activity on this subject. 149 (14.4%) students had participated in an activity that focussed the subject of conflicts of interest and 779 (77.8%) wanted more education on the subject. 701 (73.4%) were opposed to an improvement of medical studies through financial support by pharmaceutical companies, whereas 216 (21.9%) were of the opinion that students should not meet with pharmaceutical representatives. CONCLUSIONS: Unlike in other countries, like the US, most German medical faculties do not have policies that govern the interactions between medical students and pharmaceutical companies. Since most students want to be taught more about these interactions, the implementation of respective policies and lectures would be desirable.

Attitudes towards prescribing cognitive enhancers among primary care physicians in Germany.

BACKGROUND: Primary care physicians are gate keepers to the medical system having a key role in giving information and prescribing drugs to their patients. In this respect they are involved in claims of patients/clients for pharmacological Cognitive Enhancement (CE). Therefore, we studied the knowledge of primary care physicians about CE and their attitudes toward prescribing CE drugs to healthy subjects. METHODS: A self-report paper-and-pencil questionnaire and case vignettes describing a hypothetical CE drug were sent out to all 2,753 registered primary care physicians in Rhineland Palatine, Germany. 832, i.e. 30.2% filled in the questionnaire anonymously. RESULTS: 96.0% of all participating physicians had already heard about CE. However, only 5.3% stated to be very familiar with this subject and 43.5% judged themselves as being not familiar with CE. 7.0% had been asked by their clients to prescribe a drug for CE during the last week, 19.0% during the last month, and 40.8% during the last year. The comfort level to prescribe CE drugs was very low and significantly lower than to prescribe sildenafil (Viagra®). Comfort level was mainly affected by the age of the client asking for prescription of CE drugs, followed by the availability of non-pharmacological alternatives, fear of misuse of the prescribed drug by the client and the missing indication of prescribing a drug. CONCLUSIONS: Although a relatively high proportion of primary care physicians have been asked by their clients to prescribe CE drugs, only a small proportion are well informed about the possibilities of CE. Since physicians are gate keepers to the medical system and have a key role regarding a drugs' prescription, objective information should be made available to physicians about biological, ethical and social consequences of CE use.

Medical students' attitudes to and contact with the pharmaceutical industry: a survey at eight German university hospitals.

BACKGROUND: Drug companies maintain close contact with physicians. We studied the extent to which medical students are already in contact with drug companies, and their attitudes toward them. METHODS: An anonymous questionnaire containing 74 questions was distributed to 1151 medical students at eight German universities. 1038 (90.3%) of the questionnaires were filled out, returned, and evaluated. RESULTS: 12.1% of the students had never received any kind of gift from a drug company or participated in any drug company-sponsored event. 13.0% had received at least one sponsored lunch, and 24.6% had attended at least one sponsored lecture or CME event. 65.6% had received at least one non-informational gift, 50.8% an informational gift, 39.3% a reprint, and 8.6% a drug sample. 39.8% considered sponsored lectures informative and helpful, but simultaneously judged the presentation of content as biased. 45.6% and 49.7% of students, respectively, considered it all right to accept gifts because their influence was minimal in any case or because they considered themselves in a bad financial situation. 24.6% of the students thought gifts would influence their future prescribing behavior, while 45.1% thought gifts would influence their classmates' future prescribing behavior (p<0.001 for this difference). CONCLUSION: Medical students have extensive contact with the pharmaceutical industry even before they are out of medical school. Therefore, the medical school curriculum should include information about the strategies drug companies use to influence physicians' prescribing behavior, so that medical students can develop an appropriately critical attitude.

A survey of german physicians in private practice about contacts with pharmaceutical sales representatives.

BACKGROUND: Physicians and pharmaceutical sales representatives (PSR) are in regular contact. The goal of the present study is systematically to assess the kind of contacts that take place and their quality with a survey of physicians in private practice. A further goal is to determine whether alternatives to current practices can be envisioned. METHODS: 100 physicians in each of three specialties (neurology/psychiatry, general medicine, and cardiology) were surveyed with a questionnaire containing 37 questions. 208 (69.3%) questionnaires were anonymously filled out and returned. RESULTS: 77% (n = 160) of all physicians were visited by PSR at least once a week, and 19% (n = 39) every day. Pharmaceutical samples, items of office stationery and free lunches were the most commonly received gifts. 49% (n = 102) stated that they only occasionally, rarely, or never receive adequate information from PSR, and 76% (n = 158) stated that PSR often or always wanted to influence their prescribing patterns. Only 6% (n = 13) considered themselves to be often or always influenced, while 21% (n = 44) believed this of their colleagues. The physicians generally did not believe that PSR visits and drug company-sponsored educational events delivered objective information, in contrast to medical texts and non-sponsored educational events. Nonetheless, 52% (n = 108) of the physicians would regret the cessation of PSR visits, because PSRs give practical prescribing information, offer support for continuing medical education, and provide pharmaceutical samples. CONCLUSION: PSR visits and attempts to influence physicians' prescribing behavior are a part of everyday life in private medical practice, yet only a few physicians consider themselves to be susceptible to this kind of influence. A more critical attitude among physicians, and the creation of alternative educational events without drug company sponsoring, might lead to more independence and perhaps to more rational and less costly drug-prescribing practices.

The financing of drug trials by pharmaceutical companies and its consequences: part 2: a qualitative, systematic review of the literature on possible influences on authorship, access to trial data, and trial registration and publication.

BACKGROUND: In recent years, a number of studies have shown that clinical drug trials financed by pharmaceutical companies yield favorable results for company products more often than independent trials do. Moreover, pharmaceutical companies have been found to influence drug trials in various ways. This overview of current, systematic studies on this topic is intended to identify and characterize the particular aspects of the performance of a drug trial that can be affected by financial support from a pharmaceutical company. METHODS: Publications retrieved from a systematic Medline search on this topic from 1 November 2002 to 16 December 2009 were independently evaluated and selected by two of the authors. These publications were supplemented by further ones found in their references sections. RESULTS: 57 publications were included for evaluation in Parts 1 and 2 of this article. A number of studies revealed that many trials financed by pharmaceutical companies-in some cases, as many as half of all such trials-are never published. Moreover, multiple publications of the same findings were found, and some reports were found to include selectively published data. Further studies revealed evidence of other problems including incomplete trial registration, constraints on publishing rights, withheld knowledge of adverse drug reactions, and the use of ghostwriters who were supplied by the pharmaceutical companies. CONCLUSION: Financial support from a pharmaceutical company influences multiple aspects of the performance of drug trials and often leads to a favorable result for the corporate sponsor of the trial. Public access to trial protocols and results must be ensured. Moreover, more effort should be made to carry out drug trials independently, without the financial support of pharmaceutical companies.

The financing of drug trials by pharmaceutical companies and its consequences. Part 1: a qualitative, systematic review of the literature on possible influences on the findings, protocols, and quality of drug trials.

BACKGROUND: In recent years, a number of studies have shown that clinical drug trials financed by pharmaceutical companies yield favorable results for company products more often than independent trials do. Moreover, pharmaceutical companies have been found to influence drug trials in various ways. This paper provides an overview of the findings of current, systematic studies on this topic. METHODS: Publications retrieved from a systematic Medline search on this topic from 1 November 2002 to 16 December 2009 were independently evaluated and selected by two of the authors. These publications were supplemented by further ones found in their references sections. RESULTS: 57 publications were included for evaluation in Parts 1 and 2 of this article. Published drug trials that were financed by pharmaceutical companies, or whose authors declared a financial conflict of interest, were found to yield favorable results for the drug manufacturer more frequently than independently financed trials whose authors had no such conflicts. The results were also interpreted favorably more often than in independently financed trials. Furthermore, there was evidence that pharmaceutical companies influenced study protocols in a way that was favorable to themselves. The methodological quality of trials financed by pharmaceutical companies was not found to be any worse than that of trials financed in other ways. CONCLUSION: Published drug trials that are financed by pharmaceutical companies may present a distorted picture. This cannot be explained by any difference in methodological quality between such trials and trials financed in other ways.